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This meta- analysis of the r and omized controlled trials was performed to assess effects of carnitine supplementation on serum alanine aminotransferase ( ALT ) and aspartate aminotransferase ( AST ) levels . A comprehensive literature search of PubMed , Cochrane ’s library , Web of Science , Scopus , and Embase was performed up to May 2018 . From a total of 2012 articles identified initially , only 17 articles were included in the final meta- analysis to evaluate the effects of carnitine supplementation on serum levels of ALT and AST enzymes . R and om effects model meta- analysis showed that carnitine supplementation led to reduction in serum ALT ( weighted mean difference [ WMD ] − 10.25 IU/L ; 95 % CI = − 15.73 , − 4.77 ; p and AST levels ( WMD − 7.85 IU/L ; 95 % CI = − 11.85 , − 3.86 ; p that carnitine could reduce serum AST levels at dosages equal to 2000 mg/day ( p = 0.014 ) or more than 2000 mg/day ( p However , carnitine supplementation at dosages of ≤ 1000 mg/day ( p = 0.035 ) or equal to 2000 mg/day ( p = 0.013 ) result ed in significant reduction in ALT level , while doses more than 2000 mg/day did not change ALT significantly . Carnitine exerts its reducing effect on serum ALT and AST levels only when these aminotransferases are raised or when the duration of supplementation lasts at least 3 months . Results of the current meta- analysis showed that carnitine supplementation can decrease serum AST and ALT levels significantly , especially when supplementation lasts 3 months or more in patients with elevated serum aminotransferase levels	[ "In a r and omised , double-blind placebo-controlled trial , the effects of the administration of oral L-carnitine ( 2 g/day ) for 28 days were compared in the management of 51 ( carnitine group ) and 50 ( placebo group ) patients with suspected acute myocardial infa rct ion . At study entry , the extent of cardiac disease , cardiac enzymes and lipid peroxides were comparable between the groups , although both groups showed an increase in cardiac enzymes and lipid peroxides . At the end of the 28-day treatment period , the mean infa rct size assessed by cardiac enzymes showed a significant reduction in the carnitine group compared to placebo . Electrocardiographic assessment of infa rct size revealed that the QRS-score was significantly less in the carnitine group compared to placebo ( 7.4 + /- 1.2 vs 10.7 + /- 2.0 ) , while serum aspartate transaminase and lipid peroxides showed significant reduction in the carnitine group . Lactate dehydrogenase measured on the sixth or seventh day following infa rct ion showed a smaller rise in the carnitine group compared to placebo . Angina pectoris ( 17.6 vs 36.0 % ) , New York Heart Association class III and IV heart failure plus left ventricular enlargement ( 23.4 vs 36.0 % ) and total arrhythmias ( 13.7 vs 28.0 % ) were significantly less in the carnitine group compared to placebo . Total cardiac events including cardiac deaths and nonfatal infa rct ion were 15.6 % in the carnitine group vs 26.0 % in the placebo group . It is possible that L-carnitine supplementation in patients with suspected acute myocardial infa rct ion may be protective against cardiac necrosis and complications during the first 28 days", "Non-alcoholic fatty liver disease ( NAFLD ) consists of a range of complication . The disease describes clinical , para clinical and pathological conditions from simple steatosis in non-alcoholic steato hepatitis ( NASH ) to fibrosis , cirrhosis and hepato cellular carcinoma . Therefore , it is of interest to evaluate the grade of fatty liver and Liver Function Test in NAFLD patients . We collected sample s and data from 80 patients referred to gastrointestinal clinic of Emam Reza hospital with sonography diagnosed NAFLD and were evaluated in two groups in a r and omized clinical trial . The effects of L-Carnitine ( 500 mg ) prescription twice a day on liver enzymes and echogenicity changes in case group was documented and compared with the control group . The mean age of the patients was 40.7±8 in the age range of 25 to 62 years old with 66 ( 82.5 % ) male and 14 ( 17.5 % ) female patients . Data show that fatty liver changes were not significantly different in the two groups ( P=0.23 ) . It is observed that the ALT was the only enzyme with significant changes ( P=0.01 ) after a 24-week interval . It is also noted that the difference in fatty liver sonographic grading was also significant in the two groups ( P=0.0001 ) . Thus , proper therapeutic protocol s can be adopted beside diet and weight loss to control the disease trend in consideration to the significant changes observed both in enzymatic levels and sonographic grading between the two groups of patients with NAFLD", "The prevalence of and the risk factors for fatty liver have not undergone a formal evaluation in a representative sample of the general population . We therefore performed a cross-sectional study in the town of Campogalliano ( Modena , Italy ) , within the context of the Dionysos Project . Of 5,780 eligible persons aged 18 to 75 years , 3,345 ( 58 % ) agreed to participate in the study . Subjects with suspected liver disease ( SLD ) , defined on the basis of elevated serum alanine aminotransferase ( ALT ) and gamma-glutamyl-transferase ( GGT ) activity , hepatitis B surface antigen ( HBsAg ) , or hepatitis C virus (HCV)-RNA positivity , were matched with r and omly selected subjects of the same age and sex without SLD . A total of 311 subjects with and 287 without SLD underwent a detailed clinical , laboratory , and anthropometrical evaluation . Fatty liver was diagnosed by ultrasonography , and alcohol intake was assessed by using a 7-day diary . Multinomial logistic regression was used to detect risk factors for normal liver versus nonalcoholic fatty liver disease ( NAFLD ) and for alcoholic fatty liver ( AFLD ) versus NAFLD . The prevalence of NAFLD was similar in subjects with and without SLD ( 25 vs. 20 % , P = .203 ) . At multivariable analysis , normal liver was more likely than NAFLD in older subjects and less likely in the presence of obesity , hyperglycemia , hyperinsulinemia , hypertriglyceridemia , and systolic hypertension ; AFLD was more likely than NAFLD in older subjects , males , and in the presence of elevated GGT and hypertriglyceridemia , and less likely in the presence of obesity and hyperglycemia . In conclusion , NAFLD is highly prevalent in the general population , is not associated with SLD , but is associated with many features of the metabolic syndrome", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "Aim : It was the aim of this study to evaluate the effect of oral L-carnitine administration on insulin sensitivity and lipid profile in subjects with type 2 diabetes mellitus . Subjects and Methods : A r and omized , double-blind , placebo-controlled clinical trial was carried out in 12 subjects with type 2 diabetes . Six subjects received L-carnitine 1 g orally 3 times a day before meals for a period of 4 weeks . Six other individuals took a placebo for the same period of time , as the control group . Before and after the intervention , insulin sensitivity and the lipid profile were estimated . To assess insulin sensitivity , the euglycemic-hyperinsulinemic clamp technique was performed . Wilcoxon ’s signed rank and the Mann-Whitney U test were used for the statistical analyses . Results : There were no significant differences in basal clinical characteristics between the 2 groups . Insulin sensitivity and the basal lipid profile were similar . There were no significant changes in either group after the intervention in insulin sensitivity ( 3.2 ± 1.2 vs. 4.5 ± 1.7 mg/kg/min , p = 0.115 , and 3.5 ± 0.6 vs. 3.5 ± 0.4 mg/kg/min , p = 0.917 , for the placebo and L-carnitine groups , respectively ) and in lipid profile . Conclusion : L-Carnitine orally administered for a period of 4 weeks did not modify insulin sensitivity or the lipid profile ", "Background / Aims Carnitine and vitamin complex ( Godex ® ) is widely used in patients with chronic liver disease who show elevated liver enzyme in South Korea . The purpose of this study is to identify the efficacy and safety of carnitine from entecavir combination therapy in Alanine aminotransferase ( ALT ) elevated Chronic Hepatitis B ( CHB ) patients . Methods 130 treatment-naïve patients with CHB were enrolled from 13 sites . The patients were r and omly selected to the entecavir and the complex of entecavir and carnitine . The primary endpoint of the study is ALT normalization level after 12 months . Results Among the 130 patients , 119 patients completed the study treatment . The ALT normalization at 3 months was 58.9 % for the monotherapy and 95.2 % for the combination therapy ( P ALT normalization rate at 12 months was 85.7 % for the monotherapy and 100 % for the combination group ( P=0.0019 ) . The rate of less than HBV DNA 300 copies/mL at 12 months was not statistically significant ( P=0.5318 ) 75.9 % for the monotherapy , 70.7 % for the combination and it was . Quantification of HBsAg level was not different from the monotherapy to combination at 12 months . Changes of ELISPOT value to evaluate the INF-γ secretion by HBsAg showed the increasing trend of combination therapy compare to mono-treatment . Conclusions ALT normalization rate was higher in carnitine complex combination group than entecavir group in CHB . Combination group was faster than entecavir mono-treatment group on ALT normalization rate . HBV DNA normalization rate and the serum HBV-DNA level were not changed by carnitine complex treatment", "BACKGROUND / AIMS Functional and anatomical abnormalities of mitochondria play an important role in developing steatohepatitis . Carnitine is essential for enhanced mitochondrial beta oxidation through the transfer of long-chain fatty acids into the mitochondria . We examined the impact of carnitine complex on liver function and peripheral blood mitochondria copy number in NAFLD patients . METHODS Forty-five NAFLD patients were enrolled . Patients were categorized into the carnitine complex-administered group and control group . Before and 3 months after drug administration , a liver function test and peripheral blood mitochondrial DNA and 8-oxo-dG quantitive analysis were conducted . RESULTS In carnitine treatment group , ALT , AST , and total bilirubin were reduced after medication . There was no difference in AST , ALT , and total bilirubin between before and after treatment in control group . In carnitine group , peripheral mitochondrial DNA copy number was significantly increased from 158.8+/-69.5 copy to 241.6+/-180.6 copy ( p=0.025 ) . While in control group the mitochondrial copy number was slightly reduced from 205.5+/-142.3 to 150.0+/-109.7 . 8-oxo-dG level was also tended to decrease in carnitine group ( p=0.23 ) and tended to increase in control group ( p=0.07 ) . CONCLUSIONS In NAFLD , the carnitine improved liver profile and peripheral blood mitochondrial DNA copy number . This results suggest that carnitine activate the mitochondria , thereby contributing to the improvement of NAFLD", "BACKGROUND Patients with cystic acne ( CA ) on Isotretinoin ( Iso ) therapy might present muscular symptoms as side effect of the drug . Myalgia , weakness , hypotension are also some of the main characteristics of carnitine ( car ) deficiency . METHODS Two hundred and thirty ( N = 230 ) patients with CA were treated with Isotretinoin ( 0.5 mg/kg per 24 h ) . All the patients were requested to visit our out-patient department at the onset of muscular symptoms . Laboratory tests including car ( total , free , acylcarnitine ) were determined in blood and urine before treatment , at the onset of muscular symptoms and after the end of a 45 day study . Fifty percent of the patients with muscular involvement received L-carnitine ( 100 mg/kg per 24 h per os ) ( group C ) and 50 % placebo ( group P ) . RESULTS Their laboratory tests showed the well known increases of their liver enzymes and lipids , whereas car blood levels were remarkably decreased at the onset of their muscular symptoms and or at the end of the study . Their supplementation with L-car , in patients of group C ( N = 20 ) without Iso discontinuation or reduction , result ed in the disappearance of their muscular symptoms within 5 - 6 days and normalisation not only of the increased levels of their liver enzymes but also those of car , at the 45 day of their therapy . Additionally , the patients who received placebo ( group P , N = 20 ) continued complaining for mualgias . The rest of the patients ( group A , N = 190 ) did not experience any muscular symptoms , their laboratory tests showed elevation of liver enzymes and lipids and a decrease in car levels in the blood whereas a remarkable increase of car excretion was determined in their urine . CONCLUSIONS Iso therapy decreases car blood levels in patients with CA . L-car supplementation might treat liver and muscular side effects of the drug . These hopeful preliminary results need further investigation", " OBJECTIVES : Nonalcoholic steatohepatitis ( NASH ) is a known metabolic disorder of the liver . No treatment has been conclusively shown to improve NASH or prevent disease progression . The function of L-carnitine to modulate lipid profile , glucose metabolism , oxidative stress , and inflammatory responses has been shown . The aim of this study was to evaluate the effects of L-carnitine 's supplementation on regression of NASH . METHODS : In patients with NASH and control subjects , we r and omly dispensed one 1-g L-carnitine tablet after breakfast plus diet and one 1 g tablet after dinner plus diet for 24 weeks or diet alone at the same dosage and regimen . We evaluated liver enzymes , lipid profile , fasting plasma glucose , C-reactive protein ( CRP ) , tumor necrosis factor (TNF)-α , homeostasis model assessment (HOMA)-IR , body mass index , and histological scores . RESULTS : At the end of the study , L-carnitine-treated patients showed significant improvements in the following parameters : aspartate aminotransferase ( P=0.000 ) , alanine aminotransferase ( ALT ) ( P=0.000 ) , γ-glutamyl-transpeptidase ( γ-GT ) ( P=0.000 ) , total cholesterol ( P=0.000 ) , low-density lipoprotein ( LDL ) ( P=0.000 ) , high-density lipoprotein ( HDL ) ( P=0.000 ) , triglycerides ( P=0.000 ) , glucose ( P=0.000 ) , HOMA-IR ( P=0.000 ) , CRP ( P=0.000 ) , TNF-α ( P=0.000 ) , and histological scores ( P=0.000 ) . CONCLUSIONS : L-carnitine supplementation to diet is useful for reducing TNF-α and CRP , and for improving liver function , glucose plasma level , lipid profile , HOMA-IR , and histological manifestations of NASH ", "DNA single-str and breaks ( SSBs ) and their disappearance during repair incubation were determined by alkaline filter elution in freshly isolated human peripheral blood lymphocytes ( PBLs ) after in vitro treatment with either the oxygen radical-generating system of xanthine oxidase ( XOD ) plus hypoxanthine ( HYP ) or the alkylating agent N-ethyl-N'-nitrosourea ( ENU ) . The elution curves obtained with DNA from PBLs treated with XOD/HYP were markedly nonlinear , possibly as a result of a nonr and om induction of SSBs along the DNA str and s. The disappearance of XOD/HYP-induced SSBs during the initial repair period was quite slow ; only 20 + /- 7 % ( n = 6 ) of the induced SSBs had disappeared after a 2 1/2 h repair incubation . However , by 24 h the elution curves obtained with DNA from treated PBLs were indistinguishable from those obtained with DNA from nontreated control cells , indicating complete repair . Treatment of PBLs with ENU result ed in linear elution curves . Approximately 50 % of the total amount of ENU-induced SSBs had disappeared within 1 h in PBLs from most donors ; the additional SSBs were found to be persistent ( Beorrigter , M.E.T.I. , Mullaart , E. , Berends , F. , and Vijg , J. ( 1991 ) Induction and disappearance of DNA str and breaks and /or alkali-labile sites in human lymphocytes exposed to N-ethyl-N'-nitrosoureas . Carcinogenesis , 12 , 77 - 82 ) . Preincubation of PBLs with 5 mM L-carnitine , a trans-mitochondrial carrier of acetyl and long-chain acyl groups , or 5 mM acetyl-L-Carnitine , result ed in a more rapid disappearance of XOD/HYP-induced SSBs ( 48 + /- 23 % and 48 + /- 30 % respectively ) . Preincubation of PBLs with different doses of L-carnitine , before exposure to 0.5 mM ENU , increased SSB disappearance dependent on the dose and donor PBLs . In conclusion , these studies suggest that treatment with L-carnitine accelerates the disappearance of SSBs induced by oxygen radicals and alkylating agents", "The aim of this study was to investigate the effects of ALC treatment on cognitive functions in patients with severe hepatic encephalopathy . This was a r and omized , double-blind , placebo-controlled study . 61 patients with severe hepatic encephalopathy were recruited to the study . The 2 groups received either 2 g ALC twice a day ( n = 30 ) or placebo ( n = 30 ) for 90 days . Clinical and laboratory assessment , psychometric tests and automated electroencephalogram ( EEG ) analysis were performed for all patients . At the end of the study period , between the 2 groups we observed a significant difference in Everyday Memory Question naire −23.9 vs 4.4 ( p 0.001 ) , Logical Memory ( Paragraph recall ) test 22.3 vs 0.7 ( p Trail Making Test A −7.5 vs −2.6 ( p Trail Making Test B −10.5 vs −3.1 ( p Controlled Oral Word Association Test 4.2 vs 0.5 ( p Hooper test 2.6 vs 0.1 ( p 0.05 ) , Judgement of line orientation 2.8 vs 0.3 ( p Digit Cancellation time −24.5 vs −2.4 ( p prothrombin time 2 vs 2.4 ( p alanine transaminase −10.7 vs −13.6 ( p patients treated with ALC vs 72 % of patients treated with placebo showed a significant improvement in EEG . The improvement of cognitive deficits , the reduction of ammonia , and the modification of EEG in patients treated with ALC suggest that ALC could represent a new tool in the treatment of severe hepatic encephalopathy", "The purpose of this investigation was to examine the influence of L-carnitine L-tartrate ( LCLT ) supplementation using a balanced , cross-over , placebo-controlled research design on the anabolic hormone response ( i.e. , testosterone [ T ] , insulin-like growth factor-I , insulin-like growth factor-binding pro-tein-3 [ IGFBP-3 ] , and immunofunctional and immunoreac-tive growth hormone [ GHif and GHir ] ) to acute resistance exercise . Ten healthy , recreationally weight-trained men ( mean ± SD age 23.7 ± 2.3 years , weight 78.7 ± 8.5 kg , and height 179.2 ± 4.6 cm ) volunteered and were matched , and after 3 weeks of supplementation ( 2 g LCLT per day ) , fasting morning blood sample s were obtained on six consecutive days ( D1-D6 ) . Subjects performed a squat protocol ( 5 sets of 15–20 repetitions ) on D2 . During the squat protocol , blood sample s were obtained before exercise and 0 , 15 , 30 , 120 , and 180 minutes postexercise . After a 1-week washout period , subjects consumed the other supplement for a 3-week period , and the same experimental protocol was repeated using the exact same procedures . Expected exercise-induced increases in all of the hormones were observed for GHir , GHif , IGFBP-3 , and T. Over the recovery period , LCLT reduced the amount of exercise-induced muscle tissue damage , which was assessed via magnetic resonance imaging scans of the thigh . LCLT supplementation significantly ( p ) increased IGFBP-3 concentrations prior to and at 30 , 120 , and 180 minutes after acute exercise . No other direct effects of LCLT supplementation were observed on the absolute concentrations of the hormones examined , but with more undamaged tissue , a greater number of intact receptors would be available for hormonal interactions . These data support the use of LCLT as a recovery supplement for hypoxic exercise and lend further insights into the hormonal mechanisms that may help to mediate quicker recovery", "Abstract Background Hepatic steatosis is a common presentation in patients with chronic hepatitis C. Interferon α exerts both antiviral and immunomodulating actions , and influences on lipid metabolism . The aim of our study was to test whether l-carnitine reduces steatosis in patients treated with interferon and ribavirin . Patients and methods A total of 70 patients were r and omly assigned to receive either leucocyte IFN alpha at a dose of 3 MIU thrice a week plus 1,000 mg ribavirin per day for 12 months ( group A ) or IFN alpha and ribavirin at the same dose plus 2 g carnitine per day ( group B ) . Results Comparison of the two treatments showed significant differences between the mean values of the following parameters at the end of the treatment : ALT −68 vs −95 IU/ml ( P 0.05 ) , total cholesterol 0.08 vs −0.91 mmol/l ( P and triglycerides + 0.25 vs −20 mmol/l ( P ( IFN + Ribavirin + Carnitine ) than in group A ( IFN plus Ribavirin ) . When comparing those patients treated with IFN + ribavirin with those treated with IFN plus ribavirin plus carnitine , the response at the end of the treatment was 48 % vs 56 % , and the sustained response 39 % vs 46 % , respectively . Conclusions Combined treatment with l-carnitine , ribavirin and IFN alpha result ed in greater antihyperlipidaemic effects and than with ribavirin and IFN alpha alone . The results of this study suggest that l-carnitine may have a role among the reduction of steatosis strategies in patients with hepatitis C treated with IFN alpha and ribavirin ", "Abstract Background . Minimal hepatic encephalopathy ( MHE ) represents a common complication present in well-compensated cirrhotic patients that impairs patients ' daily functioning and health-related quality of life ( HRQL ) . Acetyl-l-carnitine ( ALC ) has been shown to be useful in improving blood ammonia and cognitive functions in cirrhotic patients with MHE . Objective . This study evaluated the effects of ALC treatment on HRQL and depression in patients with MHE . Study design . This was a r and omized , double-blind , placebo-controlled study . Sixty-seven patients with MHE were recruited to the study . They were r and omly assigned to two groups and received either 2 g acetyl-l-carnitine twice a day ( n = 33 ) or placebo ( n = 34 ) for 90 days . The primary efficacy measures were changes in aspartate aminotransferase , alanine aminotransferase , γ-glutamyl-transpeptidase , albumin , alkaline phosphatase , prothrombin time , and ammonia . Clinical and laboratory assessment s , psychometric tests and automated electroencephalogram ( EEG ) analysis were performed for all patients . Results . At the end of the study period , between the two groups , we observed a significant difference in physical function ( p role physical ( p general health ( p , social function ( p role emotional ( p , mental health ( p Beck Depression Inventory ( p TMT-B s ( p 0.001 ) , State Trait Inventory ( p urea ( p NH4 + ( p and bilirubin ( p that ALC treatment is associated with significant improvement in patient energy levels , general functioning and well-being . The improvement of quality of life is associated with reduction of anxiety and depression ", "BACKGROUND AND AIMS Advanced glycation end products ( AGEs ) contribute to cardiovascular disease in patients with hemodialysis ( HD ) . We have recently found that carnitine levels are inversely associated with skin AGE levels in HD patients . We examined whether L-carnitine supplementation reduced skin AGE levels in HD patients with carnitine deficiency . METHODS This was a single-center study . One hundred and two HD patients ( total carnitine levels to either oral administration of L-carnitine ( 900 mg/day ) ( n=51 ) or control ( n=51 ) . After 6 months , metabolic and inflammatory variables , including serum levels of carnitine , were measured . Skin AGE levels were determined by evaluating skin auto-fluorescence with an AGE-reader . RESULTS There were no significant differences of clinical variables at baseline between the control and L-carnitine therapy group . Thirty-two patients did not complete the assessment or treatment of the study . Oral L-carnitine supplementation for 6 months significantly increased low-density lipoprotein cholesterol ( LDL-C ) , triglycerides , total , free , and acyl carnitine levels , while it decreased alanine transaminase , acyl/free carnitine ratio , β₂-microglobulin , and skin AGE values . Change in total carnitine values from baseline ( Δtotal carnitine ) and Δfree carnitine were inversely associated with Δskin AGE levels in L-carnitine-treated patients ( p=0.036 and p=0.016 , respectively ) . In multiple regression analysis , Δfree carnitine was a sole independent determinant of Δskin AGEs ( R²=0.178 ) . CONCLUSIONS The present study demonstrated that oral L-carnitine supplementation significantly decreased skin AGE levels in HD patients with carnitine deficiency . These observations suggest that supplementation of L-carnitine might be a novel therapeutic strategy for preventing the accumulation of tissue AGEs in carnitine-deficient patients with HD" ]	411887c2-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Trigger points are promoted as an important cause of musculoskeletal pain . There is no accepted reference st and ard for the diagnosis of trigger points , and data on the reliability of physical examination for trigger points are conflicting . OBJECTIVES To systematic ally review the literature on the reliability of physical examination for the diagnosis of trigger points . METHODS MEDLINE , EMBASE , and other sources were search ed for articles reporting the reliability of physical examination for trigger points . Included studies were evaluated for their quality and applicability , and reliability estimates were extracted and reported . RESULTS Nine studies were eligible for inclusion . None satisfied all quality and applicability criteria . No study specifically reported reliability for the identification of the location of active trigger points in the muscles of symptomatic participants . Reliability estimates varied widely for each diagnostic sign , for each muscle , and across each study . Reliability estimates were generally higher for subjective signs such as tenderness ( kappa range , 0.22 - 1.0 ) and pain reproduction ( kappa range , 0.57 - 1.00 ) , and lower for objective signs such as the taut b and ( kappa range , -0.08 - 0.75 ) and local twitch response ( kappa range , -0.05 - 0.57 ) . CONCLUSIONS No study to date has reported the reliability of trigger point diagnosis according to the currently proposed criteria . On the basis of the limited number of studies available , and significant problems with their design , reporting , statistical integrity , and clinical applicability , physical examination can not currently be recommended as a reliable test for the diagnosis of trigger points . The reliability of trigger point diagnosis needs to be further investigated with studies of high quality that use current diagnostic criteria in clinical ly relevant patients	[ "& NA ; A series of health surveys are conducted every sixth to seventh year in Denmark . In the most recent survey of 2000 , a national r and om sample ( > 16 years ) was drawn from the Danish Central Personal Register . Out of the original sample 12,333 ( 74 % ) were interviewed and of these 10,066 returned a completed question naire ( SF‐36 ) . The present study includes only those who both took part in the interview and the postal question naire . Cancer patients were excluded . Persons suffering from chronic pain ( PG ) were identified through the question ‘ Do you have chronic/long lasting pain lasting 6 months or more ’ ? An overall chronic pain prevalence of 19 % was found −16 % for men and 21 % for women . Prevalence of chronic pain increased with increasing age . Persons ≥67 years had 3.9 higher odds of suffering from chronic pain than persons in the age group 16–24 years . Compared with married persons , divorced or separated persons had 1.5 higher odds of chronic pain . Odds for chronic pain were 1.9 higher among those with an education of less than 10 years compared with individuals with an education of 13 years or more . During a 14‐day period reporters of chronic pain had an average of 0.8 days ( range 0–10 ) lost due to illness compared with an average of 0.4 days ( range 0–10 ) for the control group ( CG ) ( Odds Ratio ( OR ) ) 2.0 ) . Persons with a job which required high physical strain were more likely to report chronic pain compared with those with a sedentary job ( OR 2.2 ) . The odds of quitting one 's job because of ill health were seven times higher among people belonging to the PG . A strong association between chronic pain and poor self‐rated health was also demonstrated . The PG had twice as many contacts with various health professionals compared with the CG , and the health care system was , on average , utilised 25 % more ( overall contacts ) by the PG than by the general population . Among the persons in the PG , 33 % were not satisfied with the examinations carried out in connection with their pain condition and 40 % were not satisfied with the treatment offered . Nearly 130,000 adults , corresponding to 3 % of the Danish population , use opioids on a regular basis . Opioids are used by 12 % of the PG", "& NA ; Myofascial trigger points ( TrPs ) have been clinical ly described as discrete areas of muscle tenderness presenting in taut b and s of skeletal muscle . Using well‐defined clinical criteria , prior investigations have demonstrated interrater reliability in the diagnosis of TrPs within a given muscle . No reports exist , however , with respect to the precision with which experienced clinicians can determine the anatomic locations of TrPs within a muscle . This paper details a study wherein four trained clinicians achieved statistically significant reliability ( see below ) in estimating the precise locations of latent TrPs in the trapezius muscle of volunteer subjects ( n=20 ) . To do so , the clinicians trained extensively together prior to the study . The precise anatomic location of each subject 's primary TrP was measured in a blinded fashion using a 3 dimensional ( 3‐D ) camera system . Use of this measurement system permitted the anatomic co‐ordinates of each TrP to be located without providing feedback to subsequent clinicians . The clinicians each used a pressure algometer along with patient feedback to document the sensitivity of each suspected TrP site , however unlike routine clinical practice , the algometry was performed with a double‐blinded approach hence the results were only examined post‐hoc . At the time of data collection ( algometry readings unknown ) , 16 of the 20 subjects were judged to present with a latent TrP. Subsequently , when subjected to a criterion pressure threshold value of precision , and the reliability of the TrP estimates , statistical measures of the SEM and the Generalizability coefficient ( G‐coeff ) were determined for all suspected TrP sites in the superior‐inferior , medial‐lateral and anterior‐posterior directions . The best results were determined by pooling the measurements of all 4 clinicians , however , based upon exceeding a criterion reliability threshold of 80 % , the use of just two testers was found to produce reliable results . The two‐tester condition yielded a precision of 7.5 , 7.6 and 6.5 mm ( SEM ) with reliability ( G‐coeff ) of 0.92 , 0.86 and 0.83 , respectively . Given the double‐blinded methodology , the use of pressure algometry was also found to demonstrate internal validity . The algometer responses associated with TrP estimates varied inversely with respect to the clinical group 's reliability in identify the TrP locations . To summarize , for the trapezius muscle , this study demonstrates that two trained examiners can reliably localize latent TrPs with a precision that essentially approaches the physical dimensions of the clinician 's own fingertips . Finally , it should be recognized that the ability to precisely document TrP location appears critical to the success of future studies that may be design ed to investigate the etiology and pathogenesis of this commonly diagnosed clinical disorder", "The purpose of this study was to determine the intertester reliability of assessment s of the presence of trigger points in the region of the lumbar spine of patients with low back pain ( LBP ) . A total of six trigger points described by Travell and Simons were studied . The trigger point examination procedures described by Travell and Simons were used by 12 physical therapists . R and omly paired therapists examined 50 patients for 197 trigger points . The Kappa coefficient , percent agreement , the observed proportion of positive agreement ( Ppos ) , and the observed proportion of negative agreement ( Pneg ) were used to describe reliability . Kappa values ranged from .29 to .38 . Percent agreement ranged from 76 % to 79 % . Ppos ranged from .43 to .52 . The low Kappa and Ppos values suggest different therapists are unable to reliably determine when a trigger point is present in a patient with LBP . This study suggests the usefulness of examining for the presence of trigger points in patients with LBP should be question ed", "OBJECTIVES To determine the interexaminer reliability of palpation of three characteristics of trigger points ( taut b and , local twitch response , and referred pain ) in patients with subacute low back pain , to determine whether training in palpation would improve reliability , and whether there was a difference between the physiatric and chiropractic physicians . DESIGN Reliability study . SETTING Whittier Health Campus , Los Angeles College of Chiropractic . PARTICIPANTS Twenty-six nonsymptomatic individuals and 26 individuals with subacute low back pain . INTERVENTION Twenty muscles per individual were first palpated by an expert and then r and omly by four physician examiners . MAIN OUTCOME MEASURES Palpation findings . RESULTS Kappa scores for palpation of taut b and s , local twitch responses , and referred pain were .215 , .123 , and .342 , respectively , between the expert and the trained examiners , and .050 , .118 , and .326 , respectively , between the expert and the untrained examiners . Kappa scores for agreement for palpation of taut b and s , twitch responses , and referred pain were .108 , -.001 , and .435 , respectively , among the nonexpert , trained examiners , and -.019 , .022 , and .320 , respectively , among the nonexpert , untrained examiners . CONCLUSIONS Among nonexpert physicians , physiatric or chiropractic , trigger point palpation is not reliable for detecting taut b and and local twitch response , and only marginally reliable for referred pain after training", "The presence of a trigger point is essential to the myofascial pain syndrome . This study centres on identifying clearer criteria for the presence of trigger points in the quadratus lumborum and gluteus medius muscle by investigating the occurrence and inter-rater reliability of trigger point symptoms . Using the symptoms and signs as described by Simons ' 1990 definition and two other former sets of criteria , 61 non-specific low back pain patients and 63 controls were examined in general practice by 5 observers , working in pairs . From the two major criteria of Simons ' 1990 definition only ' localized tenderness ' has good discriminative ability and inter-rater reliability ( kappa > 0.5 ) . This study does not find proof for the clinical usefulness of ' referred pain ' , which has neither of these two abilities . The criteria ' jump sign ' and ' recognition ' , on the condition that localized tenderness is present , also have good discriminative ability and inter-rater reliability . Trigger points defined by the criteria found eligible in this study allow significant distinction between non-specific low back pain patients and controls . This is not the case with trigger points defined by Simons ' 1990 criteria . Concerning reliability there is also a significant difference between the two different criteria sets . This study suggests that the clinical usefulness of trigger points is increased when localized tenderness and the presence of either jump sign or patient 's recognition of his pain complaint are used as criteria for the presence of trigger points in the M. quadratus lumborum and the M. gluteus medius", "Objectives : To investigate the test-retest reliability of the following clinical diagnostic characteristics of myofascial trigger points : taut b and , spot tenderness , jump sign , pain recognition , referred pain and local twitch responses ( LTRs ) . Design : Test-retest reliability study . Setting : This study was undertaken in an outpatient physiotherapy department . Subjects : Fifty-eight patients ( 31 males and 27 females ) with rotator cuff tendonitis were recruited into this study . Intervention : Rotator cuff muscles were assessed by an expert for the presence or absence of the main clinical diagnostic characteristics of trigger point assessment . The process was then repeated three days later by the same expert . Main measures : Outcomes included the presence or absence of : a taut b and , spot tenderness , jump sign , pain recognition , referred pain and LTRs . Results : Kappa values between testing situations for the taut b and , spot tenderness , jump sign and pain recognition were 1 . Kappa scores for referred pain ranged between 0.79 and 0.88 and for the local twitch response between 0.75 and 1 depending on the muscles under investigation . Conclusions : The presence or absence of the taut b and , spot tenderness , jump sign and pain recognition was highly reliable between sessions . Referred pain and local twitch response reliability varied depending on the muscle being studied", "Abstract The myofascial trigger point ( MTrP ) is the hallmark physical finding of the myofascial pain syndrome ( MPS ) . The MTrP itself is characterized by distinctive physical features that include a tender point in a taut b and of muscle , a local twitch response ( LTR ) to mechanical stimulation , a pain referral pattern characteristic of trigger points of specific areas in each muscle , and the reproduction of the patient 's usual pain . No prior study has demonstrated that these physical features are reproducible among different examiners , thereby establishing the reliability of the physical examination in the diagnosis of the MPS . This paper reports an initial attempt to establish the interrater reliability of the trigger point examination that failed , and a second study by the same examiners that included a training period and that successfully established interrater reliability in the diagnosis of the MTrP. The study also showed that the interrater reliability of different features varies , the LTR being the most difficult , and that the interrater reliability of the identification of MTrP features among different muscles also varies", "Simons DG , Hong C-Z , Simons LS : Endplate potentials are common to midfiber myofacial trigger points . Am J Phys Med Rehabil 2002;81:212–222 . Objective To compare the prevalence of motor endplate potentials ( noise and spikes ) in active central myofascial trigger points , endplate zones , and taut b and s of skeletal muscle to assess the specificity of endplate potentials to myofascial trigger points . Design This nonr and omized , unblinded needle examination of myofascial trigger points compares the prevalence of three forms of endplate potentials at one test site and two control sites in 11 muscles of 10 subjects . The endplate zone was independently determined electrically . Active central myofascial trigger points were identified by spot tenderness in a palpable taut b and of muscle , a local twitch response to snapping palpation , and the subject ’s recognition of pain elicited by pressure on the tender spot . Results Endplate noise without spikes occurred in all 11 muscles at trigger-point sites , in four muscles at endplate zone sites outside of trigger points ( P = 0.024 ) , and did not occur in taut b and sites outside of an endplate zone ( P = 0.000034 ) . Conclusion Endplate noise was significantly more prevalent in myofascial trigger points than in sites that were outside of a trigger point but still within the endplate zone . Endplate noise seems to be characteristic of , but is not restricted to , the region of a myofascial trigger point", "& NA ; Temporom and ibular disorders ( TMD ) diagnoses can be viewed as the most useful clinical summary for classifying subtypes of TMD . The Research Diagnostic Criteria for TMD ( RDC/TMD ) is the most widely used TMD diagnostic system for conducting clinical research . It has been translated into 18 language s and is used by a consortium of 45 RDC/TMD‐based international research ers . While reliability of RDC/TMD signs and symptoms of TMD has been amply reported , the reliability of RDC/TMD diagnoses has not . The aim of the study was to determine the reliability of clinical TMD diagnoses using st and ardized methods and operational definitions contained in the Research Diagnostic Criteria for Temporom and ibular Disorders ( RDC/TMD ) . Data came from reliability assessment trials conducted at 10 international clinical centers , involving 30 clinical examiners assessing 230 subjects . Intraclass correlation coefficients ( ICC ) were calculated to characterize the reliability . The reliability of the diagnoses was fair to good . Median ICCs for the diagnoses myofascial pain with and without limited opening were 0.51 and 0.60 , respectively . Median ICC for arthralgia was 0.47 and 0.61 for disc displacement with reduction . RDC/TMD diagnoses of disc displacement without reduction , osteoarthritis and osteoarthrosis were not prevalent enough to calculate ICC 's , but percent agreement was always > 95 % . The reliability of diagnostic classification improved when diagnoses were grouped into pain versus non‐pain diagnoses ( ICC=0.72 ) and for detecting any diagnosis versus no diagnosis ( ICC=0.78 ) . In clinical decision‐making and research , arriving at a reliable diagnosis is critical in establishing a clinical condition and a rational approach to treatment . The RDC/TMD demonstrates sufficiently high reliability for the most common TMD diagnoses , supporting its use in clinical research and decision making", "& NA ; Although neck pain is a common source of disability , little is known about its incidence and course . We conducted a population ‐based cohort study of 1100 r and omly selected Saskatchewan adults to determine the annual incidence of neck pain and describe its course . Subjects were initially surveyed by mail in September 1995 and followed‐up 6 and 12 months later . The age and gender st and ardized annual incidence of neck pain is 14.6 % ( 95 % confidence interval : 11.3 , 17.9 ) . Each year , 0.6 % ( 95 % confidence interval : 0.0–1.1 ) of the population develops disabling neck pain . The annual rate of resolution of neck pain is 36.6 % ( 95 % confidence interval : 32.7 , 40.5 ) and another 32.7 % ( 95 % confidence interval : 25.5 , 39.9 ) report improvement . Among subjects with prevalent neck pain at baseline , 37.3 % ( 95 % confidence interval : 33.4 , 41.2 ) report persistent problems and 9.9 % ( 95 % confidence interval : 7.4 , 12.5 ) experience an aggravation during follow‐up . Finally , 22.8 % ( 95 % confidence interval : 16.4 , 29.3 ) of those with prevalent neck pain at baseline report a recurrent episode . Women are more likely than men to develop neck pain ( incidence rate ratio=1.67 , 95 % confidence interval 1.08–2.60 ) ; more likely to suffer from persistent neck problems ( incidence rate ratio=1.19 , 95 % confidence interval 1.03–1.38 ) and less likely to experience resolution ( incidence rate ratio=0.75 , 95 % confidence interval 0.63–0.88 ) . Neck pain is a disabling condition with a course marked by periods of remission and exacerbation . Contrary to prior belief , most individuals with neck pain do not experience complete resolution of their symptoms and disability", "Abstract The aim of this study was to investigate the reliability between different examiners when using the axis I of the Research Diagnostic Criteria for Temporom and ibular Disorders ( RDC/TMD ) . The hypothesis was that the st and ardized RDC/TMD examination protocol enables calibrated examiners to evaluate all examination items reliably . After calibration training by the RDC/TMD calibration team including the calibration of palpation pressure and the performance of the st and ardized examination protocol , four examiners , blinded to the patients ’ medical histories examined 24 subjects in a r and omized sequence . One experienced examiner was the st and ard ( hierarchical calibration ) . The recorded measurements strictly followed the RDC/TMD . Intraclass correlation coefficients ( ICC ) , bias and precision were calculated to estimate interrater reliability . Acceptable ( 0.75≥ICC>0.4 ) to excellent ( ICC>0.75 ) reliability was found for 20 of the 23 ( 87 % ) examinations . Only sub-retrom and ibular muscle palpation and joint sound vibration recordings on lateral excursion showed poor- results ( ICC≤0.4 ) . The RDC/TMD examination protocol enables calibrated examiners to perform most ( 87 % ) examination items with satisfactory reliability . Therefore multi-site studies based on the RDC/TMD examination protocol may become feasible , keeping in mind the unsatisfactory reliability of 13 % of the items ( clicking during laterotrusion to the ipsilateral side , palpation of the posterior and subm and ibular region )", "& NA ; In a postal survey , we asked 1009 r and omly chosen individuals , age 18–84 , about their pain problems . The pain prevalence depended on what types of questions were asked . Any pain or discomfort , including even a problem of short duration , was reported by 66 % of those question ed . Forty percent reported ‘ obvious pain ’ ( pain which affected them ‘ to quite a high degree ’ or more and was ‘ like being stiff after exercise ’ or worse ) lasting more than 6 months . Pain problems of more than 6 months duration were reported far more often than short‐lasting problems . Continuous or nearly continuous pain problems were reported as frequently as problems recurring regularly or irregularly . Pains in the neck , shoulders , arms , lower back and legs were most frequent . The prevalence of ‘ obvious pain ’ in these localizations was 15–20 % . Pain was reported most frequently in the age group 45–64 , where the prevalence of ‘ obvious pain ’ was 50 % among males as well as females . Over 65 years of age the prevalence was less", "OBJECTIVES To develop a structured physical examination protocol that identifies common biomechanical and soft-tissue abnormalities for older adults with chronic low back pain ( CLBP ) that can be used as a triage tool for healthcare providers and to test the interobserver reliability and discriminant validity of this protocol . DESIGN Cross-sectional survey and examination . SETTING Older adult pain clinic . PARTICIPANTS One hundred eleven community-dwelling adults aged 60 and older with CLBP and 20 who were pain-free . MEASUREMENTS Clinical history for demographics , pain duration , previous lumbar surgery or advanced imaging , neurogenic claudication , and imaging clinical ly serious symptoms . Physical examination for scoliosis , functional leg length discrepancy , pain with lumbar movement , myofascial pain ( paralumbar , piriformis , tensor fasciae latae ( TFL ) ) , regional bone pain ( sacroiliac joint ( SIJ ) , hip , vertebral body ) , and fibromyalgia . RESULTS Scoliosis was prevalent in those with ( 77.5 % ) and without pain ( 60.0 % ) , but prevalence of SIJ pain ( 84 % vs 5 % ) , fibromyalgia tender points ( 19 % vs 0 % ) , myofascial pain ( 96 % vs 10 % ) , and hip pain ( 48 % vs 0 % ) was significantly different between groups ( P Interrater reliability was excellent for SIJ pain ( 0.81 ) , number of fibromyalgia tender points ( 0.84 ) , and TFL pain ( 0.81 ) ; good for scoliosis ( 0.43 ) , kyphosis ( 0.66 ) , lumbar movement pain ( 0.75 ) , piriformis pain ( 0.71 ) , and hip disease by internal rotation ( 0.56 ) ; and marginal for leg length ( 0.00 ) and paravertebral pain ( 0.39 ) . CONCLUSION Biomechanical and soft tissue pathologies are common in older adults with CLBP , and many can be assessed reliably using a brief physical examination . Their recognition may save unnecessary healthcare expenditure and patient suffering", "& NA ; Data from the World Health Organization 's study of psychological problems in general health care were used to examine the course of persistent pain syndromes among primary care patients . Across 15 sites in 14 countries , 3197 r and omly selected primary care patients completed baseline and 12‐month follow‐up assessment s of pain , other somatic symptoms , and anxiety and depressive disorders ( the Composite International Diagnostic Interview ) , and an assessment of occupational role disability ( the Social Disability Schedule ) . Of patients with a persistent pain condition at baseline , 49 % had not recovered 12 months later . The probability of non‐recovery varied significantly across study centers and was significantly associated with the number of pain sites at baseline . After adjustment for age , sex , and study center , baseline anxiety or depressive disorder did not predict non‐recovery of persistent pain . Among those without a persistent pain disorder at baseline , the rate of onset was 8.8 % with a significant variability in risk across centers . The baseline characteristics predicting the onset of persistent pain disorder were psychological disorder , poor self‐rated health , and occupational role disability . A persistent pain disorder at baseline predicted the onset of a psychological disorder to the same degree that a baseline psychological disorder predicted the subsequent onset of persistent pain . Persistent pain conditions are common among primary care patients , and the probability of resolution over 12 months is approximately 50 % . We found a strong and symmetrical relationship between persistent pain and psychological disorder . Impairment of daily activities appears to be a central component of that relationship", "& NA ; The overall population impact of chronic pain on work performance has been underestimated as it has often been described in terms of work‐related absence , excluding more subtle effects that chronic pain may have on the ability to work effectively . Additionally , most studies have focussed on occupational and /or patient cohorts and treatment seeking , rather than sampling from the general population . We undertook a population ‐based r and om digit dialling computer‐assisted telephone survey with participants r and omly selected within households in order to measure the impact of chronic pain on work performance . In addition , we measured the association between pain‐related disability and litigation . The study took place in Northern Sydney Health Area , a geographically defined urban area of New South Wales , Australia , and included 484 adults aged 18 or over with chronic pain . The response rate was 73.4 % . Working with pain was more common ( on an average 83.8 days in 6 months ) than lost work days due to pain ( 4.5 days ) among chronic pain participants in full‐time or part‐time employment . When both lost work days and reduced‐effectiveness work days were summed , an average of 16.4 lost work day equivalents occurred in a 6‐month period , approximately three times the average number of lost work days . In multiple logistic regression modelling with pain‐related disability as the dependent variable , past or present pain‐related litigation had the strongest association ( odds ratio (OR)=3.59 , P=0.001 ) . In conclusion , chronic pain had a larger impact on work performance than has previously been recognised , related to reduced performance while working with pain . A significant proportion were able to work effectively with pain , suggesting that complete relief of pain may not be an essential therapeutic target . Litigation ( principally work‐related ) for chronic pain was strongly associated with higher levels of pain‐related disability , even after taking into account other factors associated with poor functional outcomes", "& NA ; This study reports chronic pain prevalence in a r and omly selected sample of the adult Australian population . Data were collected by Computer‐Assisted Telephone Interview ( CATI ) using r and omly generated telephone numbers and a two‐stage stratified sample design . Chronic pain was defined as pain experienced every day for three months in the six months prior to interview . There were 17,543 completed interviews ( response rate=70.8 % ) . Chronic pain was reported by 17.1 % of males and 20.0 % of females . For males , prevalence peaked at 27.0 % in the 65–69 year age group and for females , prevalence peaked at 31.0 % in the oldest age group ( 80–84 years ) . Having chronic pain was significantly associated with older age , female gender , lower levels of completed education , and not having private health insurance ; it was also strongly associated with receiving a disability benefit ( adjusted OR=3.89 , P unemployment benefit ( adjusted OR=1.99 , P being unemployed for health reasons ( adjusted OR=6.41 , P having poor self‐rated health ( adjusted OR=7.24 , P high levels of psychological distress ( adjusted OR=3.16 , P degree of interference with daily activities caused by their pain . Prevalence of interference was highest in the 55–59 year age group in both males ( 17.2 % ) and females ( 19.7 % ) . Younger respondents with chronic pain were proportionately most likely to report interference due to pain , affecting 84.3 % of females and 75.9 % of males aged 20–24 years with chronic pain . Within the subgroup of respondents reporting chronic pain , the presence of interference with daily activities caused by pain was significantly associated with younger age ; female gender ; and not having private health insurance . There were strong associations between having interfering chronic pain and receiving disability benefits ( adjusted OR=3.31 , P being unemployed due to health reasons ( adjusted OR=7.94 , P adult Australian population , including the working age population , and is strongly associated with markers of social disadvantage" ]	411887fe-06ff-11f0-808a-c43d1ab1c353
OBJECTIVE To systematic ally review and summarize the evidence of an association between preoperative smoking status and postoperative complications elaborated on complication type . BACKGROUND The conclusions of studies examining the association between preoperative smoking and postoperative complications are inconsistent , thus there is a need for a review and meta- analysis to summarize the existing evidence . METHODS A systematic review and meta- analysis based on a search in MEDLINE , EMBASE , CINAHL , and PsycINFO . Included were original studies of the association between smoking status and postoperative complications occurring within 30 days of operation . In total , 9354 studies were identified and review ed for eligibility and data were extracted . Forest plots and summarized relative risks ( RR ) including 95 % confidence intervals ( CIs ) were estimated for various complication types . RESULTS Of the 9354 identified studies , 107 studies were included in the meta-analyses and based on these , 157 data sets were extracted . Preoperative smoking was associated with an increased risk of various postoperative complications including general morbidity ( RR=1.52 , 95 % CI : 1.33 - 1.74 ) , wound complications ( RR=2.15 , 95 % CI : 1.87 - 2.49 ) , general infections ( RR=1.54 , 95 % CI : 1.32 - 1.79 ) , pulmonary complications ( RR=1.73 , 95 % CI : 1.35 - 2.23 ) , neurological complications ( RR=1.38 , 95 % CI : 1.01 - 1.88 ) , and admission to intensive care unit ( RR=1.60 , 95 % CI : 1.14 - 2.25 ) . Preoperative smoking status was not observed to be associated with postoperative mortality , cardiovascular complications , bleedings , anastomotic leakage , or allograft rejection . CONCLUSIONS Preoperative smoking was found to be associated with an increased risk of the following postoperative complications : general morbidity , wound complications , general infections , pulmonary complications , neurological complications , and admission to the intensive care unit	[ "Background This prospect i ve study followed patients who underwent breast reductions to determine the influence of smoking and the amount of tissue removed on postoperative wound infections . Methods Patients who had received breast reductions were considered eligible for the study . The study excluded postbariatric patients and those with ongoing clinical infections , a recent antibiotic course , or systemic diseases that could impair tissue oxygenation . Smokers were instructed to quit smoking at least 4 weeks before surgery . Results By March 2004 , the study had enrolled 87 patients . Postoperative infections were present in 24 cases ( 27.9 % ) . Infections included 16 in smokers ( 37.2 % ) , 8 in nonsmokers ( 18.2 % ; p 0.85 kg ; 70 % ) , and 10 in patients with small resections ( 14.9 % ; p overall estimated cigarettes smoked ( mean , 146,000 ; range , 29,200–228,125 vs mean , 10,950 ; range , 9,125–54,750 ; p number of pack years ( mean , 20 ; range , 4–31 vs mean , 2 ; range , 1–8 ; p amount of tissue removed ( mean , 0.9 kg ; range , 0.5–2 kg vs mean , 0.5 kg ; range , 0.2–1.4 kg ; p amount of tissue removed . Conclusions Smoking and the amount of tissue removed are important issues in aesthetic breast surgery that need to be addressed accurately by the plastic surgeon . If future larger studies confirm these data , surgeons could have a simple and easy method for stratifying patients according to their risk for the development of wound infections and for prescribing specific preventive measures", "Background : In this prospect i ve study , the authors followed patients who underwent aesthetic abdominoplasty to determine the influence of smoking on the occurrence of postoperative wound infections . Methods : Patients who underwent aesthetic abdominoplasty were considered eligible for the study . The authors excluded postbariatric patients , those with ongoing clinical infections , those receiving a recent antibiotic course , and those with systemic diseases such as arteriosclerosis and diabetes mellitus . Smokers were advised to quit smoking at least 4 weeks before surgery . Results : Starting in February of 2004 , the authors enrolled 84 patients . Postoperative infections were present in 13 patients ( 15.5 percent ) and were superficial in 10 ( 77 percent ) . All but one occurred in smokers . These had a certain number of cigarettes smoked per day , years of smoking , and higher estimated overall number of smoked cigarettes when postoperative infections were present . The relative risk of smoking on infections was 12 . A cutoff value of approximately 33,000 overall cigarettes smoked determined 3.3 percent false-positive and 0 percent false-negative rates . Conclusions : Smoking is an important issue in aesthetic surgery that needs to be accurately addressed during the preoperative interview . In the future , the analysis of smoke-related , easy-to-gather variables such as the estimated overall number of cigarettes smoked until surgery could help stratify patients according to their risk of manifesting infections", "Background The extent to which lifestyle factors such as tobacco consumption and obesity affect the outcome after inguinal hernia surgery has been poorly studied . This study was undertaken to assess the effect of smoking , smokeless tobacco consumption and obesity on postoperative complications after inguinal hernia surgery . The second aim was to evaluate the effect of tobacco consumption and obesity on the length of hospital stay . Methods A cohort of 12,697 Swedish construction workers with prospect ively collected exposure data on tobacco consumption and body mass index ( BMI ) from 1968 onward were linked to the Swedish inpatient register . Information on inguinal hernia procedures was collected from the inpatient register . Any postoperative complication occurring within 30 days was registered . In addition to this , the length of hospitalization was calculated . The risk of postoperative complications due to tobacco exposure and BMI was estimated using a multiple logistic regression model and the length of hospital stay was estimated in a multiple linear regression model . Results After adjusting for the other covariates in the multivariate analysis , current smokers had a 34 % ( OR 1.34 , 95 % CI 1.04 , 1.72 ) increased risk of postoperative complications compared to never smokers . Use of “ Swedish oral moist snuff ” ( snus ) and pack-years of tobacco smoking were not found to be significantly associated with an increased risk of postoperative complications . BMI was found to be significantly associated with an increased risk of postoperative complications ( P = 0.04 ) . This effect was mediated by the underweighted group ( OR 2.94 ; 95 % CI 1.15 , 7.51 ) . In a multivariable model , increased BMI was also found to be significantly associated with an increased mean length of hospital stay ( P smoking or using snus , and the mean length of hospitalization after adjusting for the other covariates in the model . ConclusionS moking increases the risk of postoperative complications even in minor surgery such as inguinal hernia procedures . Obesity increases hospitalization after inguinal hernia surgery . The Swedish version of oral moist tobacco , snus , does not seem to affect the complication rate after hernia surgery at all", "BACKGROUND Previous studies have linked smoking and alcohol consumption to a considerable disease burden and large healthcare expenditures . However , findings from studies based on individual level data are sparse and inconclusive . Our objective was to assess the association between alcohol consumption , smoking and patterns of hospitalization , defined as admission and duration of hospitalization . METHODS The study was based on 12 698 men and women , aged 20 years or more , enrolled in the Copenhagen City Heart Study . We related smoking and alcohol to hospital admission from any cause , smoking- and alcohol-related diseases and duration of hospitalization in a two-part r and om effects model . RESULTS Smoking status was strongly associated with admission and duration of hospitalization . For smoking-related admissions , odds ratios ( OR ) of 2.77 ( 95 % CI 2.13 - 3.59 ) in men and 6.30 ( 95 % CI 4.80 - 8.26 ) in women were observed among smokers of > 20 g/day compared to never-smokers . For any admission ( excl . smoking-related causes ) , corresponding ORs were 1.32 ( 95 % CI 1.15 - 1.51 ) and 1.80 ( 95 % CI 1.58 - 2.06 ) , respectively . In men , a U-shaped association between alcohol consumption and risk of admission was found , both regarding any admission and admissions due to alcohol-related diseases . Alcohol was associated with alcohol-related admissions in women but not with duration of hospitalization . CONCLUSIONS Smoking was associated with increased risk of hospital admission and duration of hospitalization . A U-shaped relation was observed for alcohol consumption and risk of hospitalization in men , but no effect on duration was observed . In women , however , alcohol consumption was only vaguely associated with admission and duration of hospitalization", "BACKGROUND An association between smoking and impaired wound healing has been reported in retrospective studies . The smoking status of a surgical patient may be confounded by social and medical parameters . We have evaluated the effect of smoking in a test wound in volunteers , with special reference to a reliable scientific match between smokers and nonsmokers . METHODS In a prospect i ve open study with blinded assessment , 19 smoking ( 20 cigarettes/day ) and 18 nonsmoking healthy volunteers were matched with respect to baseline characteristics . The deposition of total protein and mature collagen ( expressed as hydroxyproline ) was assessed in an exp and ed polytetrafluoroethylene wound healing model implanted subcutaneously for 10 days . RESULTS The nonsmokers had a 1.8 times higher median amount of hydroxyproline than the smokers ( p deposition of hydroxyproline was negatively correlated with the consumption of tobacco both before ( r = -0.44 ; p < 0.01 ) and during the study ( r = -0.48 ; p < 0.005 ) . The impairment was specific for the production of collagenous proteins and not other proteins . CONCLUSIONS The synthesis of subcutaneous collagen in smokers is specifically impeded , indicating an impaired wound-healing process . Because mature collagen is the main determinator of strength of an operative wound , the results support the view that patients should be advised to stop smoking before an operation", "BACKGROUND Coughing during emergence from general anaesthesia may be detrimental , particularly after cervical spine surgery . We compared the effect of propofol or sevoflurane anaesthesia on the incidence and severity of coughing during recovery in patients undergoing cervical spine surgery via an anterior approach . As a secondary aim , we also evaluated the influences of smoking and estimated residual anaesthetic agent concentrations on coughing . METHODS Thirty-four patients were enrolled in a r and omized prospect i ve , double-blind study to receive either propofol ( PPF ) or sevoflurane ( SEVO ) for maintenance of anaesthesia . The decision to perform tracheal extubation was based on specified criteria , including resumption of spontaneous respiration and consciousness . During emergence from anaesthesia and extubation , coughing was observed and grade d at predefined times . RESULTS The incidence of severe coughing was higher in the SEVO group than in the PPF group ( 59 % and 6 % , respectively ) , and also in smokers than in non-smokers ( 50 % and 17 % , respectively ) . The peak incidence of coughing was at tracheal extubation . The probability of coughing was influenced by the estimated residual concentration of anaesthetic agents at extubation , except for smokers in the SEVO group who were at the highest risk of coughing . CONCLUSIONS The incidence of coughing after cervical spine surgery when tracheal extubation is performed according to clinical criteria is lower after propofol anaesthesia compared with sevoflurane anaesthesia . Smokers are at increased risk of coughing , independently of the type of anaesthesia maintenance . Higher residual concentrations of anaesthetic agents decrease the probability of coughing , except for smokers anaesthetized with sevoflurane", "HYPOTHESIS Anastomotic leaks following elective colorectal resections increase morbidity , mortality , and the need for additional interventions . An accurate underst and ing of risk factors would potentially reduce anastomotic leaks and /or allow appropriate selection of patients for diverting stomas . DESIGN Prospect i ve review of patient and operative characteristics that contribute to anastomotic leaks . SETTING Fifty-one sites within the United States ( May 2002-March 2005 ) . PATIENTS Six hundred seventy-two patients who participated in a trial comparing preoperative antimicrobials in elective open colorectal surgery . MAIN OUTCOME MEASURES Anastomotic leaks were diagnosed using clinical findings and were confirmed with imaging . We examined 20 variables possibly affecting anastomotic healing in univariate and multivariate analyses . RESULTS There were 24 anastomotic leaks in 672 patients ( 3.6 % ) undergoing elective colorectal resection . There were 10 deaths ( 1.5 % ) . A baseline albumin level of less than 3.5 g/dL ( to convert to grams per liter , multiply by 10 ) ( P = .04 ) and male sex ( P = .03 ) were associated with anastomotic leaks in both univariate and multivariate analyses ( adjusted odds ratios , 2.56 and 3.12 , respectively ) . Increased duration of surgery ( SD , 60 minutes ; odds ratio , 1.53 ; 95 % confidence interval , 1.06 - 2.22 ; P = .03 ) and steroid use at the time of surgery ( odds ratio , 3.85 ; 95 % confidence interval , 1.24 - 11.93 ; P = .02 ) were significant in univariate analysis . Surgical procedure with rectal resection ; prophylaxis with ertapenem ( vs cefotetan ) ; or history of obesity , tobacco use , or diabetes was not associated with anastomotic leaks . CONCLUSIONS Significant risk factors for anastomotic leaks include low preoperative serum albumin level , steroid use , male sex , and increased duration of surgery . Appreciation of risk factors provides a rational basis for temporary diversion", "OBJECTIVES The overall benefit of carotid endarterectomy ( CEA ) is dependent on the outcome from the procedure . However , many reports are from selected centres and not population -based . The aim of this study was to assess the 30-day complication rate for a whole country and also to determine independent risk factors for serious complications . MATERIAL S AND METHODS One thous and five hundred and eighteen CEA were retrospectively review ed , covering principally all the CEAs in Sweden , during a three year period . Indications for surgery were ; minor stroke 34 % , TIA 34 % , amaurosis fugax 18 % , asymptomatic 11 % and others 3 % . Data were collected from the Swedish Vascular Registry ( Swedvasc ) . Combined cohort and case-control methodology was used . RESULTS Registered complications were ; 43 permanent strokes , 32 transient strokes ( 30-day permanent stroke and death rate were 4.3 % ( 65/1518 ) . Significant risk factors in multivariate analyses were the indication for surgery ( minor stroke vs. other indications ) ( p=0.02 , RR=1.38 ) , diabetes ( p=0.02 , RR=1.41 ) , cardiac disease ( p contralateral occlusion ( p local neurological complication ( facial paresis ) . CONCLUSION This national audit demonstrated population -based data on complication rates after CEA well comparable with previous r and omised trials . The validity of the Swedvasc data was confirmed . Combined cohort and case-control methodology was useful in analysing risk factors for serious perioperative complications", "Smoking is the world 's leading cause of premature mortality responsible for an estimated 5 million deaths each year . Although the negative health implication s of cigarette smoking in the nontransplant setting are well recognized , the effect on patient and graft survival post liver transplantation remains unclear . The aim of this study was therefore to assess the influence of smoking on morbidity and mortality following liver transplantation . We performed a retrospective single-center case-note study of 136 consecutive patients who underwent elective liver transplantation between January 1 , 1996 and December 31 , 2000 . Patients were defined as active smokers ( 23 % ) , exsmokers ( 18 % ) , or life-long nonsmokers ( 58 % ) on the basis of documentation at the time of transplant assessment . Active smoking was associated with increased all-cause mortality post transplant , with estimated 1- , 5- , and 10-year survival of 94 % , 68 % , and 54 % , respectively , versus 94 % , 83 % , and 77 % for nonsmokers ( P = 0.04 ) . A multivariate Cox proportional hazards model identified smoking as an independent predictor of death ( hazard ratio 2.23 , 95 % confidence interval 1.08 - 4.61 , P = 0.03 ) . Active smokers demonstrated increased cardiovascular-specific mortality ( P = 0.01 ) and sepsis-specific mortality ( P = 0.02 ) but not malignancy-related mortality ( P = 0.61 ) and had graft survival similar to that of nonsmokers ( P = 0.88 ) . Exsmokers did not have an increased risk of death ( P = 0.134 ) . In conclusion , active smokers at time of assessment have increased mortality post liver transplantation , which is non-graft-related and appears to be a result of increased cardiovascular-related and sepsis-related death . Prospect i ve studies are required to assess the impact of smoking cessation on long-term outcome", "Background Postoperative pulmonary complications ( PPC ) are the most frequently observed complications following lung resection , of which pneumonia and atelectasis are the most common . PPCs have a significant clinical and economic impact associated with increased observed number of deaths , morbidity , length of stay and associated cost . The aim of this study was to assess the incidence and impact of PPCs and to identify potentially modifiable independent risk factors . Methods A prospect i ve observational study was carried out on all patients following lung resection via thoracotomy in a regional thoracic centre over 13 months . PPC was assessed using a scoring system based on chest x-ray , raised white cell count , fever , microbiology , purulent sputum and oxygen saturations . Results Thirty-four of 234 subjects ( 14.5 % ) had clinical evidence of PPC . The PPC patient group had a significantly longer length of stay ( LOS ) in hospital , high dependency unit ( HDU ) LOS , higher frequency of intensive care unit ( ITU ) admission and a higher number of hospital deaths . Older patients , body mass index ( BMI ) ≥30 kg/m2 , preoperative activity preoperative forced expiratory volume in 1 s ( FEV1 ) and predicted postoperative ( PPO ) FEV1 were all significantly ( p 75 years , BMI ≥30 kg/m2 , ASA ≥3 , smoking history and COPD were significant independent risk factors in the development of PPC ( p<0.05 ) . Conclusion The clinical impact of PPCs is marked . Significant independent preoperative risk factors have been identified in current clinical practice . Potentially modifiable risk factors include BMI , smoking status and COPD . The impact of targeted therapy requires further evaluation", "Objective The aim of this study was to identify risk factors for surgical-site infections ( SSIs ) in patients with head and neck cancer su bmi tted to major clean-contaminated surgery . Study Design This is a prospect i ve study conducted in a tertiary cancer center hospital . Subjects and Methods This study includes 258 patients su bmi tted to a major clean-contaminated head and neck oncologic surgery . Results The overall SSI rate was 38.8 % . The univariate analysis showed the following significant risk factors : race , tobacco consumption , clinical stage , comorbidities , time duration of the surgical procedure , and flap reconstruction . The final model by logistic regression identified the following independent predictors for SSI : tobacco consumption ( odds ratio [ OR ] = 2.96 ) , presence of metastatic lymph nodes ( OR = 2.05 ) , flap reconstruction ( OR = 2.20 ) , and antimicrobial prophylaxis exceeding 48 hours ( OR=1.89 ) . Conclusion The high-risk patients for SSI in head and neck oncologic surgery were those with cancer at advanced stages , those who were smokers , those presenting comorbidities , those who needed major reconstruction of the surgical wound , or those who were su bmi tted to inadequate antibiotic prophylaxis", "We evaluated the relationship between PPC and various putative risk factors in a prospect i ve longitudinal study of 1,000 patients undergoing abdominal surgery . Transient sub clinical events were excluded by defining PPC as positive clinical findings in combination with either positive sputum microbiology , unexplained pyrexia , or positive chest roentgenographic findings . The overall incidence of PPC was 23.2 percent ( 232/1,000 ) . Multivariate analysis identified seven factors which were associated with PPC : ASA classification greater than 2 , upper abdominal surgery , residual intraperitoneal sepsis , age greater than 59 years , BMI greater than 25 , preoperative hospital stay greater than 4 days , and colorectal or gastroduodenal surgery ( overall F score = 33.5 , p less than 0.0001 ) . The ASA classification was the most powerful indicator of risk in both the univariate and the multivariate analyses . The combination of ASA classification greater than 1 and age greater than 59 years identified 88 percent ( 205 of 232 ) of the patients who developed PPC . These findings provide clinicians and clinical investigators with a simple means of identifying patients who are at high risk of PPC after abdominal surgery", "QUESTION Can the risk of developing postoperative pulmonary complications be predicted after upper abdominal surgery ? DESIGN Prospect i ve observational study . PARTICIPANTS 268 consecutive patients undergoing elective upper abdominal surgery who received st and ardised pre- and postoperative prophylactic respiratory physiotherapy . OUTCOME MEASURES Predictors were 17 preoperative and intraoperative risk factors . A postoperative pulmonary complication was diagnosed when four or more of the following criteria were present : radiological evidence of collapse/consolidation , temperature > 38 degrees C , oxyhaemoglobin saturation sputum production , sputum culture indicating infection , raised white cell count , abnormal auscultation findings , or physician 's diagnosis of pulmonary complication . RESULTS 35 participants ( 13 % ) developed postoperative pulmonary complications . Five risk factors predicted postoperative pulmonary complications : duration of anaesthesia ( OR 4.3 , 95 % CI 1.7 to 10.8 ) ; surgical category ( OR 2.3 , 95 % CI 1.1 to 4.7 ) ; current smoking ( OR 2.1 , 95 % CI 1.0 to 4.5 ) ; respiratory co-morbidity ( OR 2.1 , 95 % CI 1.0 to 4.4 ) ; and predicted maximal oxygen uptake ( OR 2.0 , 95 % CI 1.0 to 4.3 ) . A clinical rule for predicting the development of postoperative pulmonary complications predicted 82 % of participants who developed complications . The odds of high risk participants developing pulmonary complications were 8.4 ( 95 % CI 3.3 to 21.3 ) times that of low risk participants . CONCLUSION This clinical rule for predicting the risk of developing postoperative pulmonary complications from five risk factors may prove useful in prioritising postoperative respiratory physiotherapy . Further research is needed to vali date the rule", "BACKGROUND We sought to assess the effect of smoking on early outcome following valve surgery . METHODS This is a retrospective review of a prospect ively collected departmental data base of all patients who underwent isolated aortic and /or mitral valve surgery ( replacement and /or repair ) . Our cohort consisted of 590 patients stratified into three groups : current smokers ( n = 94 ) , ex-smokers ( n = 243 ) , and nonsmokers ( n = 253 ) . RESULTS There were no significant differences in the in-hospital mortality between the three groups . Likewise , the length of both hospital and intensive care unit stays were similar among the three groups with a similar rate of postoperative complications . These findings remained statistically not significant , even after adjusting for potential confounders such as age , gender , etc . CONCLUSION Smoking does not seem to be associated with an increased early postoperative risk in patients undergoing valve surgery . However , because of the known effect of smoking on the risk of cardiovascular disease and because the effect of smoking on long-term survival in patients undergoing valve surgery remains unknown , patients should still be encouraged to quit smoking", "Surgical site infections ( SSI ) are undesired and troublesome complications after spinal surgery . The reported infection rates range from 0.7 to 11.9 % , depending on the diagnosis and the complexity of the procedure . Besides operative factors , patient characteristics could also account for increased infection rates . Because the medical , economic and social costs of SSI are enormous , any significant reduction in risks will pay dividends . The purpose of this study is to compare patients who developed deep SSI following lumbar or thoracolumbar spinal fusion with a r and omly selected group of patients who did not develop this complication in order to identify changeable risk factors . With a case – control analysis nested in a historical cohort of patients who had had a spinal fusion between January 1999 and December 2008 , we identified 36 cases with deep SSI ( CDC criteria ) . Information regarding patient-level and surgical-level risk factors was derived from st and ardized but routinely recorded data and compared with those acquired in a r and om selection of 135 uninfected patients . Univariate analyses and a multivariate logistic regression were performed . The overall rate of infection in 1,615 procedures ( 1,568 patients ) was 2.2 % . A positive history of spinal surgery was associated with an almost four times higher infection rate ( OR = 3.7 , 95 % BI = 1.6–8.6 ) . The risk of SSI increased with the number of levels fused , patients with diabetes had an almost six times higher risk and smokers had more than a two times higher risk for deep SSI . The most common organism cultured was Staphylococcus aureus . All infected patients underwent at least one reoperation , including an open débridement and received appropriate antibiotics to treat the organism . Patients who had had a previous spinal surgery are a high-risk group for infection compared with those that never had surgery . Total costs associated with preventive measures are substantial and should be compensated by health care insurance companies by means of separate clinical pathways . High-risk patients should be informed about the increased risk of complications ", "BACKGROUND : We assessed the prevalence of substance use among patients undergoing coronary artery bypass graft and valve surgery in northwest Iran . We evaluated the postoperative complications and in-hospital mortality of patients with substance dependence and abuse . METHODS : In this prospect i ve , observational study , we interviewed 600 patients during the preoperative visit in a tertiary referral educational hospital in northwest Iran . The definition of substance abuse and dependence was according to DSM-IV criteria . Postoperative complications and in-hospital mortality of patients with substance ( cigarette , opium , and alcohol ) dependence and abuse were compared with those in control patients who did not use these substances . RESULTS : In 600 studied patients , the prevalence of cigarette smoking was 42.1 % ( ex-smokers 26.0 % and current smokers 16.1 % ) , prevalence of opium use was 12.0 % ( opium abuse 7.0 % and opium dependence 5.0 % ) , and alcohol consumption was 8.1 % ( alcohol abuse 7.4 % and alcohol dependence 0.7 % ) . The prevalence of cigarette smoking was 58.9 % in men and 7.6 % in women ( P = 0.001 ) . Postoperative cardiac complications in current smokers ( 21.5 % ) and ex-smokers ( 20.5 % ) were not significantly different from the control group ( 28.2 % ) . Also , pulmonary complications were not different in current smokers ( 24.7 % ) and ex-smokers ( 17.9 % ) from the control group ( 26.8 % ; P = 0.196 ) . However , in men , pulmonary complications in current smokers were more prevalent than in the control group ( P = 0.044 ) . In opium and alcohol dependents and abusers , postoperative complications were not statistically different from the control group ( all P values > 0.05 ) . No increase was observed regarding in-hospital mortality in patients with substance use . CONCLUSIONS : In cardiac surgery patients in northwest Iran , the prevalence of cigarette smoking is relatively low ( very low in women ) , as is alcohol use , compared with Western countries ; however , opium use is twice as prevalent . We found higher pulmonary complication rates in men who smoked , but no increase in postoperative cardiopulmonary complications and in-hospital mortality rates in patients who abused opium and consumed alcohol", "BACKGROUND The objective of this study was to determine the significant differences in preoperative and operative characteristics , and postoperative outcomes in patients having coronary artery bypass grafting ( CABG ) who are smokers and in those who are not smokers . METHODS Data were collected prospect ively in all ( 2916 ) patients having their first CABG . The patients were cared for in a regional medical center by private physicians . No operations were denied because of smoking status . Smokers differed from nonsmokers in several characteristics . RESULTS Analysis of morbidity and mortality showed no instance in which smokers fared worse than nonsmokers . Stepwise logistic regression analysis showed that smoking was not predictive of mortality . Smoking was not predictive of morbidity except that it was predictive of less probability of need for intra-aortic balloon pump ( 7.5 % in nonsmokers and 4.7 % in smokers ) . We then created groups of smokers and nonsmokers that were individually matched for age and sex . Analysis of the matched groups of smokers and nonsmokers showed that there was no significant difference in the incidence or magnitude of preoperative and operative factors except that recent myocardial infa rct ion was more common in smokers . Nonsmokers had greater weight , body mass index ( obesity ) , and ejection fraction . There was no difference in smokers and nonsmokers in mortality or morbidity at the 99 % confidence level . CONCLUSION We conclude that there is no need to delay CABG for the patients who are smokers", "Study Design . A retrospective case control analysis of 48 cases of postoperative infection following spinal procedures . Objectives . Spinal procedures that became infected after surgery were analyzed to identify the significance of preoperative and intraoperative risk factors . Characterization of the nature and timing of the infections was also performed . Summary of Background Data . The rate of postoperative infection following spinal surgery varies widely depending on the nature of the procedure and the patient ’s diagnosis . Preoperative comorbidities and risk factors also influence the likelihood of infection . Methods . A review of 1629 procedures performed on 1095 patients revealed that a postoperative infection developed in 48 patients ( 4.4 % ) . Data regarding preoperative and intraoperative risk factors were gathered from patient charts for these and a r and omly selected control group of 95 uninfected patients . For analysis , these patient groups were further divided into adult and pediatric subgroups , with an age cutoff of 18 years . Preoperative risk factors review ed included smoking , diabetes , previous surgery , previous infection , steroid use , body mass index , and alcohol abuse . Intraoperative factors review ed included staging of procedures , estimated blood loss , operating time , and use of allograft or instrumentation . Results . The majority of infections occurred during the early postoperative period ( less than 3 months ) . Age > 60 years , smoking , diabetes , previous surgical infection , increased body mass index , and alcohol abuse were statistically significant preoperative risk factors . The most likely procedure to be complicated by an infection was a combined anterior/posterior spinal fusion performed in a staged manner under separate anesthesia . Infections were primarily monomicrobial , although 5 patients had more than 4 organisms identified . The most common organism cultured from the wounds was Staphylococcus aureus . All patients were treated with surgical irrigation and débridement , and appropriate antibiotics to treat the cultured organism . Conclusions . Aggressive treatment of patients undergoing complex or prolonged spinal procedures is essential to prevent and treat infections . Underst and ing a patient ’s preoperative risk factors may help the physician to optimize a patient ’s preoperative condition . Additionally , awareness of critical intraoperative parameters will helpto optimize surgical treatment . It may be appropriate to increase the duration of prophylactic antibiotics or implement other measures to decrease the incidence of infection for high risk patients", "PURPOSE Morbidity after radical cystectomy is common and associated with increased health care re source use . Accurate characterization of complications after cystectomy , associated patient specific risk factors , and perioperative processes of care are essential to directing changes in perioperative management that will reduce morbidity and improve the quality of patient care . MATERIAL S AND METHODS The National Surgical Quality Improvement Program ( NSQIP ) is a prospect i ve quality management initiative of 123 Veterans Affairs Medical Centers nationwide . The NSQIP collects clinical information , intraoperative data and outcomes on a wide variety of surgical procedures from multiple surgical disciplines . Since 1991 , 2,538 radical cystectomy procedures have been captured by the NSQIP . Modeling using logistic regression was performed to identify patient specific risk factors and perioperative process measures associated with postoperative morbidity . RESULTS Of the 2,538 subjects at least 1 postoperative complication developed in 774 ( 30.5 % ) . The most frequent complication was ileus ( 10 % ) . Several factors were associated with the development of a complication , including age , dependent functional status , preoperative dyspnea , preoperative acute renal failure , chronic steroid use , preoperative alcohol consumption , American Society of Anesthesiology score , use of general anesthetic , operative time , intraoperative blood requirement and surgeon level of training . CONCLUSIONS Morbidity remains high after cystectomy with 30.5 % of subjects experiencing at least 1 complication . Measurable patient specific risk factors and perioperative processes associated with postoperative morbidity following cystectomy are now delineated which allows for improved risk stratification , patient counseling , and the development of novel processes that may incrementally reduce risk and improve outcomes", "BACKGROUND The aim of the study was to assess both mortality and morbidity following resection of mid and low rectal cancers in a French prospect i ve multicentric study . PATIENTS From June to September 2002 , consecutive patients undergoing resection for cancer of the mid- or lower rectum were prospect ively included in a multicentric study . Both postoperative mortality and morbidity were recorded . Multivariate statistical analysis was performed in order to assess risk factors predictive of postoperative morbidity . RESULTS 238 patients with a mean age of 66 + /- 13 years ( range : 26 - 88 ) were included . Neoadjuvant radiotherapy was performed in 68 % of the patients . Total mesorectal excision was performed in 218 patients ( 92 % ) , of whom 151 ( 63 % ) had a sphincter saving procedure . Six patients died ( 2.5 % ) . Overall postoperative morbidity rate was 43 % , including anastomotic leakage ( 11 % ) and reoperation ( 5 % ) . Mean hospital-in-stay was 20 + /- 16 days ( range : 3191 ) . Four independent risk factors of morbidity were found : perioperative fecal contamination ( OR = 3.9 [ 1.1 ; 13.5 ] ) , mean operating time longer than 6 hours ( OR = 4.5 [ 1.7 ; 12.1 ] ) , ASA score > 2 ( OR = 3.2 [ 1.6 ; 7.9 ] ) , and smocking ( OR = 3.3 [ 1.2 ; 8.9 ] ) . CONCLUSIONS Resection of cancer involving the middle or lower rectum with sphincter saving procedures was possible in two-thirds of the patients and was associated with 2.5 % mortality and 43 % morbidity", " The association between cigarette smoking and necrosis of flaps and full-thickness grafts was analyzed in 220 patients . Review of a series of 916 flaps and full-thickness grafts revealed 44 patients in whom some degree of tissue necrosis occurred . These patients with necrosis were age and gender matched with 176 controls r and omly selected from the remaining 872 patients . Current high-level smokers , that is those smoking one or more packs per day , had necrosis develop approximately three times more frequently than never smokers , low-level smokers ( less than one pack per day ) , or former smokers ( 95 % confidence interval , 1.2 to 8.2 ) . Former smokers ( relative risk , 1.4 ; 95 % confidence interval , 0.6 to 3.2 ) and low-level smokers ( relative risk , 1.1 ; 95 % confidence interval , 0.2 to 6.1 ) were at a negligible increased risk for necrosis that was not significantly different from never smokers . Once tissue necrosis developed , the median percent of the visible flap or graft tissue that necrosed was approximately threefold greater among current smokers ( regardless of the number of packs per day smoked ) than never smokers", "Study Design . This is a multivariate analysis of a prospect ively collected data base . Objective . To determine preoperative , intraoperative , and patient characteristics that contribute to an increased risk of postoperative wound infection in patients undergoing spinal surgery . Summary of Background Data . Current literature sites a postoperative infection rate of approximately 4 % ; however , few have completed multivariate analysis to determine factors which contribute to risk of infection . Methods . Our study identified patients who underwent a spinal decompression and fusion between 1997 and 2006 from the Veterans Affairs ’ National Surgical Quality Improvement Program data base . Multivariate logistic regression analysis was used to determine the effect of various preoperative variables on postoperative infection . Results . Data on 24,774 patients were analyzed . Wound infection was present in 752 ( 3.04 % ) patients , 287 ( 1.16 % ) deep , and 468 ( 1.89 % ) superficial . Postoperative infection was associated with longer hospital stay ( 7.12 vs. 4.20 days ) , higher 30-day mortality ( 1.06 % vs. 0.5 % ) , higher complication rates ( 1.24 % vs. 0.05 % ) , and higher return to the operating room rates ( 37 % vs. 2.45 % ) . Multivariate logistic regression identified insulin dependent diabetes ( odds ratios [ OR ] = 1.50 ) , current smoking ( OR = 1.19 ) ASA class of 3 ( OR = 1.45 ) or 4 to 5 ( OR = 1.66 ) , weight loss ( OR = 2.14 ) , dependent functional status ( 1.36 ) preoperative HCT 6 hours ( OR = 1.40 ) as statistically significant predictors of postoperative infection . Conclusion . Using multivariate analysis of a large prospect ively collected data from the National Surgical Quality Improvement Program data base , we identified the most important risk factors for increased postoperative spinal wound infection . We have demonstrated the high mortality , morbidity , and hospitalization costs associated with postoperative spinal wound infections . The information provided should help alert clinicians to presence of these risks factors and the likelihood of higher postoperative infections and morbidity in spinal surgery patients", "Background : Acute lung injury ( ALI ) is a serious postoperative complication with limited treatment options . A preoperative risk-prediction model would assist clinicians and scientists interested in ALI . The objective of this investigation was to develop a surgical lung injury prediction ( SLIP ) model to predict risk of postoperative ALI based on readily available preoperative risk factors . Methods : Secondary analysis of a prospect i ve cohort investigation including adult patients undergoing high-risk surgery . Preoperative risk factors for postoperative ALI were identified and evaluated for inclusion in the SLIP model . Multivariate logistic regression was used to develop the model . Model performance was assessed with the area under the receiver operating characteristic curve and the Hosmer-Lemeshow goodness-of-fit test . Results : Out of 4,366 patients , 113 ( 2.6 % ) developed early postoperative ALI . Predictors of postoperative ALI in multivariate analysis that were maintained in the final SLIP model included high-risk cardiac , vascular , or thoracic surgery , diabetes mellitus , chronic obstructive pulmonary disease , gastroesophageal reflux disease , and alcohol abuse . The SLIP score distinguished patients who developed early postoperative ALI from those who did not with an area under the receiver operating characteristic curve ( 95 % CI ) of 0.82 ( 0.78–0.86 ) . The model was well calibrated ( Hosmer-Lemeshow , P = 0.55 ) . Internal validation using 10-fold cross-validation noted minimal loss of diagnostic accuracy with a mean ± SD area under the receiver operating characteristic curve of 0.79 ± 0.08 . Conclusions : Using readily available preoperative risk factors , we developed the SLIP scoring system to predict risk of early postoperative ALI ", "BACKGROUND The aim of this study was to investigate the influence of cigarette smoking on wound-healing in patients undergoing breast reduction . METHODS In our prospect i ve study , 50 patients ( 25 smokers , 25 nonsmokers ) scheduled for breast reduction have been evaluated . Urine cotinine levels were measured to analyse perioperative smoking habits . Urine sample s were taken preoperatively and on the fourth postoperative day . Cotinine as a metabolite of nicotine allows precise evaluation of nicotine exposure . To assess the progress of woundhealing we classified secreting , instable , inflamed or necrotic wound conditions , which required a dressing after the tenth postoperative day as impaired wound healing . For statistical analysis non-parametrical tests for independent and dependent data were used . RESULTS Ten of 25 smokers presented impaired wound healing compared to 4 of 25 nonsmokers . The median cotinine level of smokers was 1964 (783/3963)ng/cc preoperatively and 432 (148/1695)ng/cc postoperatively . Nonsmokers had a preoperative cotinine level of 18 (7/37)ng/cc and 15 (4/34)ng/cc postoperatively . Smokers who developed impaired wound-healing showed higher levels of cotinine pre- ( 2117 ng/cc ) and especially postoperatively ( 485 ng/cc ) compared to smokers with regular woundhealing ( 1614 ng/cc and 389 ng/cc ) . Both differences in cotinine levels were statistically significant ( p=0.03 and p=0.02 ) . CONCLUSIONS The data of the present study confirm the negative effect of smoking on wound healing in patients undergoing breast reduction", "OBJECTIVE To examine the effect of preoperative smoking behavior on postoperative pulmonary complications . DESIGN Prospect i ve cohort study . SETTING The Veterans Administration Medical Center , Syracuse , NY . PARTICIPANTS Patients scheduled for noncardiac elective surgery ( n=410 ) . MEASUREMENTS AND RESULTS Smoking status was determined by self-report . Postoperative pulmonary complications were determined by systematic extraction of medical record data . Postoperative pulmonary complications occurred in 31 of 141 ( 22.0 % ) current smokers , 24 of 187 ( 12.8 % ) past smokers , and 4 of 82 ( 4.9 % ) never smokers . The odds ratio ( OR ) for developing a postoperative pulmonary complication for current smokers vs never smokers was 5.5 ( 95 % confidence interval [ CI ] , 1.9 to 16.2 ) and 4.2 ( 95 % CI , 1.2 to 14.8 ) after adjustment for type of surgery , type of anesthesia , abnormal chest radiograph , chronic cough , history of pulmonary disease , history of cardiac disease , history of COPD , education level , pulmonary function , body mass index , and age . Current smokers who reported reducing cigarette consumption prior to surgery were more likely to develop a complication compared with those who did not ( adjusted OR=6.7 , 95 % CI , 2.6 to 17.1 ) . CONCLUSIONS Current smoking was associated with a nearly sixfold increase in risk for a postoperative pulmonary complication . Reduction in smoking within 1 month of surgery was not associated with a decreased risk of postoperative pulmonary complications", "PURPOSE H and assisted laparoscopic surgery ( HALS ) provides benefits similar to st and ard laparoscopy but generally requires a larger incision . We assessed the nature of and risk factors for incisional complications after HALS . MATERIAL S AND METHODS All patients who underwent HALS at our institution from February 1997 through December 2003 were included in a prospect i ve and retrospective review to assess postoperative wound complications . Literature regarding wound complications associated with open surgery and st and ard laparoscopy was review ed . RESULTS A total of 424 consecutive procedures performed on 422 patients were evaluated . Postoperative HALS incision site complications included 29 infections ( 6.8 % ) , 15 hernias ( 3.5 % ) and 2 dehiscences ( 0.5 % ) . Multivariate logistic regression models revealed that HALS incision site hernias were associated with current or past tobacco smoking ( 6.0 % , p = 0.04 ) , with a trend toward significance for diabetes mellitus ( 14 % , p = 0.07 ) , male gender ( 5.3 % , p = 0.08 ) and renal failure ( 16 % , p = 0.08 ) . HALS incision site infections were associated with omission of perioperative antibiotics ( 13 % , p = 0.007 ) , obesity ( 12 % , p = 0.03 ) and increased operative time ( 252 vs 222 minutes in patients with and without infection , respectively , p = 0.001 ) . CONCLUSIONS Our findings suggest that wound infections and hernias occur less frequently with HALS than with open surgery , but more often than with st and ard laparoscopy . Certain patient comorbidities ( eg obesity ) , modifiable risk factors ( eg smoking status ) and procedural variables ( eg omission of perioperative antibiotics or length of procedure ) may adversely influence HALS wound complications . This information can be used to decide between HALS and st and ard laparoscopic approaches in particular patients", "Background : Although attempts have been made to identify the risk factors leading to complications after combined skin-sparing mastectomy and immediate prosthetic breast reconstruction , hardly any criteria are available to preoperatively distinguish patients in whom such an eventful postoperative course may be expected . Therefore , the authors wanted to establish which factors increase the risk of surgical complications to such a level as to adjust their indications for immediate breast reconstruction after skin-sparing mastectomy . Methods : The authors prospect ively studied the clinical relevance of six patient-related and nine procedure-related characteristics as potential risk factors for a complicated surgical outcome in 400 combined procedures in 309 patients by univariate and multivariate logistic regression analysis . Risk factors that proved significantly correlated with loss of implant by both analyses were accepted as clinical selection criteria that distinguish potential c and i date s with an unacceptably high risk of such loss . Results : Mild complications occurred significantly more often in patients who were older than the mean age of 43 years and in breasts that were more than average sized or operated on by a fellow in oncologic surgery . Implants were lost significantly more often in patients who were obese or smoked and in breasts that were more than average sized . Conclusions : The clinical ly relevant increase of risk of implant loss should lead to reluctance to perform combined skin-sparing mastectomy and immediate prosthetic breast reconstruction in obese patients who smoke ( 32 percent loss ) and in those with more than average sized breasts ( 27 percent loss )" ]	4118883a-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Calcium channel blockers are a heterogeneous class of drugs , including dihydropyridine and non-dihydropyridine subgroups , commonly used in the treatment of hypertension . A systematic review of the 24-hour time course of the blood pressure-lowering effect has not been published . OBJECTIVES To assess how much variation there is in hourly systolic and diastolic blood pressure lowering by dihydropyridine calcium channel blockers over a 24-hour period in people with hypertension aged 18 years or over , with baseline systolic blood pressure of at least 140 mmHg or diastolic blood pressure of at least 90 mmHg , or both . SEARCH METHODS We performed electronic search es of the Cochrane Central Register of Controlled Trials ( CENTRAL ) ( Issue 1 , 2014 ) , MEDLINE ( 1946 to February 2014 ) , EMBASE ( 1974 to February 2014 ) , and Clinical Trials.gov ( to February 2014 ) . We also screened references of published studies and review s to identify additional trials . SELECTION CRITERIA We included all r and omized , placebo-controlled trials assessing the hourly effects of dihydropyridine calcium channel blockers by ambulatory blood pressure monitoring in adults with hypertension with a follow-up of at least three weeks . DATA COLLECTION AND ANALYSIS Two authors independently selected the included trials , evaluated the risk of bias , and analyzed the data . MAIN RESULTS We included 16 r and omized controlled trials of dihydropyridine calcium channel blockers in this systematic review , with 2768 r and omized participants . Drugs studied included amlodipine , lercanidipine , m and ipine , nifedipine , and felodipine ( all administered once daily ) and nicardipine ( administered twice daily ) . We analyzed and presented data by hour post dose . The blood pressure-lowering effect was stable over time ; there were no clinical ly important differences in blood pressure-lowering effect of calcium channel blockers between each hour for either systolic blood pressure ( estimated mean hourly differences ranged between 9.45 mmHg and 13.2 mmHg ) or diastolic blood pressure ( estimated mean hourly differences ranged between 5.85 mmHg and 8.5 mmHg ) . However , there was a moderate risk of bias for this finding . Once-daily dihydropyridine calcium channel blockers appeared to lower blood pressure by a relatively constant amount throughout the 24-hour dosing interval . AUTHORS ' CONCLUSIONS Six dihydropyridine calcium channel blockers studied in this review lowered blood pressure by a relatively similar amount each hour over the course of 24 hours . The benefits and harms of this pattern of blood pressure lowering are unknown . Further trials are needed with accurate recording of time of drug intake and with reporting of st and ard deviation of blood pressure at each hour . We did not attempt to assess adverse effects in this review due to the lack of reporting and the short duration of follow-up	[ "The antihypertensive efficacy of the angiotensin II receptor blocker olmesartan medoxomil has been shown to compare favourably with that of other antihypertensive agents . This r and omized , double-blind study compared the antihypertensive efficacy of the starting dose of olmesartan medoxomil with that of the calcium channel blocker amlodipine besylate ( amlodipine ) in subjects with mild-to-moderate hypertension . Following a 4-week , single-blind , placebo run-in period , 440 subjects aged ⩾18 years were r and omized to the starting dose of olmesartan medoxomil ( 20 mg/day ) , amlodipine ( 5 mg/day ) , or placebo for 8 weeks . Subjects were evaluated by 24-h ambulatory blood pressure monitoring ( ABPM ) and by seated cuff blood pressure ( BP ) measurements at trough . The primary end point was the change from baseline in mean 24-h diastolic blood pressure ( DBP ) by ABPM at Week 8 . Secondary end points included change from baseline in mean 24-h ambulatory systolic blood pressure ( SBP ) at 8 weeks , change from baseline in mean seated trough cuff DBP and SBP measurements , and response and control rates for DBP . Olmesartan medoxomil and amlodipine produced significantly greater reductions in ambulatory and seated DBP and SBP compared with placebo . Mean reductions in ambulatory and seated BP were similar between the two active agents ; however , in the olmesartan medoxomil group , significantly more patients achieved the SBP goal of tolerated at the recommended starting dose . Although amlodipine was associated with a higher incidence of oedema , this did not reach statistical significance . Olmesartan medoxomil is an effective antihypertensive agent , with BP-lowering efficacy at the starting dose similar to that of amlodipine , and is associated with more patients achieving the rigorous BP goals of SBP < 130 mmHg and DBP < 85 mmHg", "Objective To evaluate the antihypertensive effect of lercanidipine once a day at three different doses ( 2.5 , 5 and 10 mg ) by clinic and ambulatory blood pressure . Methods After 3 weeks of a placebo run-in , 243 mild to moderate essential hypertensives ( mean ± SD age 51 ± 8 years ) were r and omly allocated to lercanidipine at 2.5 , 5 or 10 mg or a placebo for 4 weeks , in a double-blind parallel-group design . At the end of each period , supine clinic blood pressure ( st and ard sphygmomanometry ) and 24 h ambulatory blood pressure ( Spacelabs 90207 ) were measured . The duration and homogeneity of the antihypertensive effect of the active drug compared with placebo over 24 h was evaluated by calculating the smoothness index , the ratio of the mean of the 24 hourly blood pressure changes to the corresponding SD . The higher the smoothness index , the greater and the smoother is the antihypertensive effect of a drug over the 24 h. Results In 211 patients with valid clinic blood pressure data at the end of treatment , larger systolic/diastolic blood pressure reductions were found in the 5 mg ( 10 ± 12/8 ± 6 mmHg ; P ) lercanidipine groups than in the placebo ( 5 ± 11/4 ± 8 mmHg ) and 2.5 mg lercanidipine ( 7 ± 12/6 ± 7 mmHg ) groups . In 105 patients with complete 24 h ambulatory blood pressure recordings , there were significantly ( P and placebo ( 2 ± 6/1 ± 4 mmHg ) groups . The reduction in 24 h blood pressure with 5 mg lercanidipine ( 6 ± 7/4 ± 5 mmHg ) was significantly greater compared with placebo for diastolic pressure only , and when hourly average blood pressure changes were considered , this reduction did not extend to the final hours of the dosing interval . No significant changes in the clinic or 24 h heart rate were induced by placebo or lercanidipine . The smoothness index was significantly ( P mg lercanidipine and placebo ( 0.2 ± 0.5 and 0.3 ± 0.7 for systolic and 0.1 ± 0.4 and 0.2 ± 0.7 for diastolic blood pressure ) than for the 5 and 10 mg doses ( 0.7 ± 1 and 1 ± 0.7 for systolic and 0.7 ± 1 and 1 ± 0.9 for diastolic blood pressure ) . Conclusions At a dose of 10 mg , lercanidipine had a significant and durable antihypertensive effect over 24 h , but at 5 mg , the effect was less consistent and did not last 24 h. There was no clinical ly relevant reduction in clinic or ambulatory blood pressure with 2.5 mg lercanidipine , and the effect was superimposable on that of placebo", "The study was to compare the effects of amlodipine ( calcium channel antagonist ) , chlorthalidone ( diuretic ) , and placebo in adults more than 50 years of age with stage 1 isolated systolic hypertension ( ISH ) . After a 4-week placebo run-in phase , 150 patients were r and omly assigned in a double-blind fashion to treatment with 5 mg of amlodipine ( n = 48 ) , 15 mg of chlorthalidone ( n = 50 ) , or placebo ( n = 52 ) . Patients who failed to meet the systolic blood pressure ( BP ) reduction goal by week 4 had their dose increased to 10 mg of amlodipine or 30 mg of chlorthalidone , and maintained at this increased dose for 12 weeks . Results showed a mean reduction ( mean + /- SD ) in sitting systolic BP from baseline to the last treatment visit of -14.6+/-12.2 mm Hg ( 95 % confidence interval [ CI ] -18.2 , -11.0 ) , -14.0+/-13.46 mm Hg ( 95 % CI -17.8 , -10.2 ) , and -3.4+/-11.83 mm Hg ( 95 % CI -6.7 , -0.1 ) for the amlodipine , chlorthalidone , and the placebo treatment groups , respectively . Both active treatments showed significantly greater reductions than the placebo group ( P amlodipine , 69 % of the chlorthalidone , and 25 % of the placebo-treated patients reached the protocol defined systolic BP goal ( P = .001 ) . Both active treatment groups showed a trend of better systolic BP response in older patients ( > or = 65 years ) . Secondary efficacy measures including pulse pressure , st and ing systolic , diastolic , and the 24-h ambulatory BP were also statistically significantly improved for both active treatments at the end of treatment , except for chlorthalidone in st and ing diastolic BP . Adverse events that occurred during the study were as expected and were well tolerated . The results of this study support the efficacy and safety of amlodipine and chlorthalidone for the treatment of stage 1 ISH during 20 weeks of treatment", "Summary . To evaluate the effect of manidipine 10 mg on 24-hour ambulatory blood pressure ( BP ) and heart rate ( HR ) in very elderly hypertensive patients , 54 patients aged 76–89 years ( mean age 81.8 years ) with systolic blood pressure ( SBP ) > 160 mmHg and diastolic blood pressure ( DBP ) > 90 mmHg were studied . After a 4-week placebo washout period , patients were r and omized to receive manidipine 10 mg or placebo , both administered once daily for 8 weeks . Patients were checked after the initial run-in placebo phase and every 4 weeks thereafter . At each visit casual BP and HR were measured . At the end of the placebo period and after 8 weeks of active treatment , noninvasive 24-hour ambulate blood pressure measurement ABPM was performed . Manidipine significantly lowered casual sitting and st and ing SBP ( P and DBP ( P decrease in 24-hour SBP and DBP values ( P ) , daytime SBP and DBP ( P and night-time SBP ( P and DBP ( P antihypertensive activity throughout the 24-hour dosing interval , without effect on the circadian BP profile . The trough/peak ratio was 0.67 for SBP and 0.59 DBP . No statistically significant change in HR was observed . The treatment was well tolerated , and there were no serious side effects . In conclusion , in very elderly hypertensive patients , once-daily administration of manidipine 10 mg was well tolerated and effective in reducing casual as well ambulatory BP", "Objective Olmesartan medoxomil is an angiotensin II receptor blocker with similar antihypertensive efficacy as the calcium channel blocker amlodipine besylate in patients with mild-to-moderate hypertension . In addition to a drug 's ability to lower blood pressure , the effectiveness of the agent in enabling patients to achieve specific blood pressure targets is an important clinical consideration . This secondary analysis of a r and omized , double-blind study compared the efficacy of olmesartan medoxomil with that of amlodipine besylate in achieving ambulatory blood pressure goals among patients with mild-to-moderate hypertension . Methods Following a 4-week placebo run-in , 440 study participants aged ≥18 years were r and omized to olmesartan medoxomil ( 20 mg/day ) , amlodipine besylate ( 5 mg/day ) , or placebo for 8 weeks . The proportion of participants achieving specific systolic and diastolic ambulatory blood pressure goal levels was calculated by dividing the number of participants who had achieved a particular blood pressure goal by the total number of patients in the intent-to-treat population . Results After 8 weeks of treatment , a mean 24-h ambulatory blood pressure of the olmesartan medoxomil group ( 18.1 and 30.4 % , respectively ) than in the amlodipine besylate ( 7.0 and 14.0 % , respectively ) or placebo ( 1.9 % for both ) groups . The target daytime ambulatory blood pressure of the olmesartan medoxomil group than in the amlodipine besylate group ( 15.8 vs. 5.8 % , respectively ; P of olmesartan medoxomil and amlodipine besylate produced similar mean reductions in blood pressure . In this sub analysis of the blood pressure data from that primary publication , however , olmesartan medoxomil therapy was shown to result in a greater proportion of patients achieving specific ambulatory blood pressure goals than therapy with amlodipine besylate . As blood pressure goal attainment may be of more direct clinical relevance than numerical blood pressure lowering , the achievement of blood pressure goals should be a key efficacy parameter assessed in clinical trials of antihypertensive medications", "Background Evaluation of combination therapy with antihypertensive agents by clinic blood pressure ( BP ) measurements may yield results that differ from out-of-office BP readings . This is of clinical relevance because out-of-office BP values are of prognostic importance . We studied the effects of combining telmisartan and amlodipine on ambulatory BP in patients with stages 1–2 hypertension . Methods We conducted an 8-week , placebo-controlled , double-blind , 4 × 4 factorial design trial in which 562 patients with clinic diastolic BP at least 95 and 119 mmHg or less were r and omized to receive telmisartan ( 0 , 20 , 40 , or 80 mg ) and /or amlodipine ( 0 , 2.5 , 5 , or 10 mg ) . Ambulatory BP monitoring was performed at baseline and after 8 weeks of treatment ; the end points of interest were the changes from baseline in 24-h systolic and diastolic BP . Secondary end points included the proportion of responders ( ≥10 mmHg BP reduction from baseline and /or of telmisartan and amlodipine lowered 24-h BP to a larger extent than the corresponding monotherapies at all doses . Mean reductions from baseline in 24-h BP for the combination of the highest doses of telmisartan ( 80 mg ) and amlodipine ( 10 mg ) were −22.4/−14.6 versus −11.9/−6.9 mmHg for amlodipine ( 10 mg ) and −11.0/−6.9 mmHg for telmisartan ( 80 mg ) ( P addition , BP response and control rates ( 24-h BP that telmisartan and amlodipine in combination provide substantial 24-h BP efficacy that is superior to either monotherapy in patients with stages 1 and 2 hypertension", "Background Previous studies have suggested that psychological interventions may be effective in reducing blood pressure . Using rigorous methodology and 24-hour monitoring of ambulatory blood pressure , we compared 2 psychological interventions with treatment using a first-line antihypertensive drug in terms of their efficacy in lowering blood pressure in patients with mild primary hypertension . Methods In this prospect i ve , open-label r and omized controlled trial ( RCT ) , 65 adult patients with mild , uncomplicated hypertension were r and omly assigned to receive one of the following interventions for 12 weeks : ( 1 ) pharmacotherapy with hydrochlorothiazide 12.5 titrated to 25 mg/d ; ( 2 ) individualized behavioural psychotherapy , consisting of ten 1-hour sessions of stress reduction training with a psychologist ; or ( 3 ) self-help psychotherapy , consisting of a 1.5-hour session with a psychologist and then daily sessions that involved reading a self-help manual and listening to an audiotape . The primary outcome measure was mean change in ambulatory blood pressure from baseline to week 12 . Resting blood pressure readings were taken in the clinic , and adverse events were recorded . Results Monitoring of ambulatory blood pressure over 24 hours showed that hydrochlorothiazide therapy significantly reduced both systolic and diastolic blood pressure relative to baseline , and that this reduction was significantly greater than that achieved with either individualized behavioural psychotherapy or self-help psychotherapy ( mean reduction [ st and ard error ; SE ] −11.03 [ 2.53 ] / −6.06 [ 1.56 ] mm Hg v. −0.08 [ 2.38 ] / 0.29 [ 1.47 ] mm Hg v. −1.23 [ 2.83 ] / −0.71 [ 1.75 ] mm Hg , respectively ; p = 0.01 ) . Neither form of psychological therapy significantly lowered 24-hour ambulatory blood pressure relative to baseline . Conclusion For patients with primary elevated blood pressure , 2 psychological interventions did not lower 24-hour ambulatory blood pressure , whereas hydrochlorothiazide reduced blood pressure , as expected . The findings of this RCT represent an important addition to the evidence for health care practitioners and for patients seeking psychological interventions to reduce blood pressure", "Summary Nifedipine GITS ( Gastro-Intestinal Therapeutic System ) is a recently launched long-acting formulation of nifedipine . The aim of the Italian Nifedipine GITS Study was to determine the duration of the antihypertensive effect of once-daily nifedipine GITS in out patients with essential hypertension . After a 2-week placebo run-in period , 126 patients with mild to moderate essential hypertension ( diastolic BP 95 to 114 mm Hg ) were r and omised to receive nifedipine GITS 30 mg ( n = 42 ) , nifedipine GITS 60 mg ( n = 42 ) or placebo ( n = 42 ) , once daily in a double-blind fashion for 4 weeks . At the end of the run-in and treatment periods , ambulatory BP monitoring was performed ( Spacelabs 90202 or 90207 device ) to provide regular 15-minute BP readings for 24 to 36 hours . In the 81 patients with at least 24 hours of valid ambulatory BP data , the average systolic and diastolic BP changes after treatment with nifedipine GITS 30 mg ( n = 25 ) , nifedipine GITS 60 mg ( n = 28 ) and placebo ( n = 28 ) were −16.5/−10.8 , −16.3/−10.0 and + 0.4/+0.9 mm Hg , respectively . BP changes with nifedipine GITS differed significantly ( p placebo . Heart rate was not significantly altered by nifedipine GITS . The effects of nifedipine GITS and placebo on ambulatory BP 24 hours and 36 hours after the last dose were evaluated in 56 patients with complete 36-hour ambulatory BP profiles . After 24 hours , both doses of nifedipine GITS caused significant ( p . After 36 hours , the reduction in ambulatory BP induced by nifedipine GITS was less pronounced than after 24 hours ; the changes in systolic BP produced by both nifedipine GITS doses were still significant ( p the change in diastolic BP was significant only after the 60 mg dose ( p 0.05).Trough : peak ratios of the antihypertensive effect of nifedipine GITS were calculated by comparing the highest average hourly BP reduction between 2 and 6 hours postdose ( peak reduction ) and the BP change at 24 hours postdose ( trough reduction ) in the 81 patients with valid 24-hour ambulatory BP data . Trough : peak ratios were 90.5 % ( systolic BP ) and 76.3 % ( diastolic BP ) for nifedipine GITS 30 mg , and 109.3 % ( systolic BP ) and 98.6 % ( diastolic BP ) for nifedipine GITS 60 mg . The ratios were further increased if placebo-induced BP changes were taken into account . In conclusion , the antihypertensive effect of nifedipine GITS is maintained for more than 24 hours postdose , and is uniform over this period , without any undue imbalance between the peak BP effect and that observed immediately before the subsequent dose", "Amlodipine is a new long-acting calcium antagonist that has a long half-life and appears to be suitable for once-daily administration . A double-blind , r and omized , parallel , placebo-controlled study was conducted to evaluate the effect of amlodipine on ambulatory blood pressures in hypertensive patients . The study consisted of a 4-week single-blind placebo run-in phase , followed by 4 weeks of double-blind therapy . Ambulatory blood pressure was measured for 24 h at the end of the placebo run-in phase and after double-blind therapy . Sixteen patients were r and omized to receive either amlodipine 5 mg or placebo in a 2:1 ratio . Amlodipine 5 mg daily significantly reduced supine and st and ing blood pressure 24 h postdose . Ambulatory blood pressure recordings revealed adequate blood pressure control throughout the 24-h dosing interval . Amlodipine was well tolerated and only two patients reported side effects -- neither was withdrawn from therapy . No treatment-related abnormalities were noted . It was concluded that amlodipine 5 mg daily was effective antihypertensive therapy throughout the 24-h dosing period in the patients studied , and it was well tolerated", "STUDY OBJECTIVE To evaluate the antihypertensive effects and tolerability of a sustained release preparation of nicardipine ( NIC SR ) , a dihydropyridine calcium channel antagonist . DESIGN AND INTERVENTIONS After at least 1 week without receiving antihypertensive medications and 2 weeks of single-blind placebo treatment , the patients were r and omized to receive in a double-blind fashion , either placebo or NIC SR 30 , 45 , or 60 mg twice daily at 12-h intervals for 12 weeks . Supine and st and ing blood pressure were measured in all patients and 24-h ambulatory blood pressure monitoring was performed in a subset of 75 patients at baseline during treatment with single-blind placebo and during the double-blind treatment period . SETTING Academic and private hypertension research clinics . PATIENTS Two hundred sixty-four patients with supine diastolic blood pressures of 95 to 114 mm Hg , ranging in age from 22 to 75 years and in weight from 50 to 137 kg , approximately evenly divided by gender ; one third were black . RESULTS In comparison with placebo , all doses of NIC SR significantly reduced systolic and diastolic blood pressures , with a trend toward greater effects from 45 to 60 mg twice daily than with 30 mg twice daily . At all doses , reduction of blood pressure from baseline levels was fully apparent within the first 2 weeks of therapy and was maintained throughout the remaining 10 weeks of the trial . Ambulatory blood pressure monitoring demonstrated that the antihypertensive effect was maintained throughout the dosing interval . Adverse effects were primarily extensions of pharmacologic activity ( eg , pedal edema , flushing ) . Six percent of the placebo group and 10 percent of the combined NIC SR groups experienced at least one adverse event that was judged to be probably related to therapy . Withdrawals due to unacceptably high blood pressure totaled 5 percent of the combined NIC SR groups and 25 percent of the placebo group . CONCLUSIONS Sustained-release nicardipine at a dose of 30 to 60 mg every 12 h provided effective and generally well-tolerated antihypertensive control throughout the day in most patients with mild-to-moderate essential hypertension", "The blood pressure response to a new sustained-release formulation of nifedipine was evaluated in an 8-week , double-blind , placebo-controlled study . Twenty-nine patients with mild essential hypertension were r and omized to receive placebo ( N = 9 ) , 30 mg nifedipine ( N = 10 ) , or 60 mg nifedipine ( N = 10 ) . During treatment , 30-mg and 60-mg doses of nifedipine administered once daily decreased office blood pressures from 137/98 + /- 8/2 mm Hg and 141/98 + /- 15/2 mm Hg at baseline , respectively , to 126/89 + /- 9/7 mm Hg and 126/86 + /- 6/7 mm Hg ( P less than .005 ) . Noninvasive automatic ambulatory blood pressure monitoring demonstrated a marginally significant ( P less than .10 ) reduction in the mean 24-hour blood pressure of 2/6 + /- 8/8 mm Hg and 5/6 + /- 9/9 mm Hg for patients taking 30 mg and 60 mg nifedipine once daily , respectively . Diastolic blood pressure load ( the percentage of ambulatory diastolic blood pressure readings greater than 90 mm Hg ) during 24 hours was decreased by 41 % and 35 % , with 30 mg and 60 mg nifedipine administered once daily , respectively . No significant dose response to nifedipine at these dose levels was observed . Although the once-daily formulation of nifedipine achieved effective control of office blood pressure , similar control was not observed in awake and 24-hour periods in all patients", "We conducted a r and omized placebo-controlled double-blind study in 40 hypertensive subjects to assess the antihypertensive effect of a new galenic form of nicardipine administered at a dosage of 50 mg twice daily for 3 weeks . Regardless of whether blood pressure was measured by st and ard mercury sphygmomanometer , non-ambulatory automatic oscillometry or a Remler ambulatory blood pressure recorder , it dropped by a significantly larger amount in the nicardipine group than in the placebo group . In the control group , a placebo effect was observed with the ambulatory diastolic blood pressure recording , whereas it was not observed with hospital blood pressure measurements , especially when using the serial measurements performed for 30 min by an automatic recorder . The fall in blood pressure measured with the Remler recorder was correlated with the fall measured 10 - 20 min during one acute intravenous nicardipine perfusion before the trial , although the correlation coefficients do not suggest clinical ly relevant predictability of nicardipine efficacy at the individual level . The present findings support the need for controlled double-blind trials with careful office blood pressure measurements", "Certain high-risk population s , such as diabetics and blacks , have sustained elevation in blood pressure and heart rate throughout the day and night , with blunting of the usual diurnal variability pattern . This may contribute to their higher incidence of left ventricular hypertrophy ( blacks ) and cardiovascular complications ( diabetics ) . Hypertensives who maintain a diurnal pattern of blood pressure variation still exhibit higher daytime and nocturnal blood pressure levels than normotensives . Thus , to achieve maximum effectiveness in treating hypertension , 24-hour control of blood pressure is necessary . Antihypertensive agents should effectively reduce blood pressure consistently throughout a 24-hour period . The objective of this study was to assess the effects of amlodipine , 5 mg once daily , on blood pressure measured by 24-hour ambulatory monitoring in a r and omized , double-blind , placebo-controlled single-site study . Patients with mild-to-moderate essential hypertension were r and omized to receive amlodipine ( n = 11 ) or placebo ( n = 5 ) in a 2:1 ratio . A 4-week single-blind placebo run-in period was followed by a 4-week double-blind phase . Ambulatory monitoring of blood pressure was carried out for 24 hours at the end of each 4-week phase . Patients receiving amlodipine had significantly lower blood pressure compared with placebo 24 hours after the last dose ( supine blood pressure -25.1/-10.1 mm Hg ; st and ing blood pressure -21.2/-9.7 mm Hg ) after 4 weeks of treatment . This effect was clearly demonstrated by the 24-hour postdose measurement and the mean blood pressure over the 24-hour interval as measured by ambulatory recordings . ( ABSTRACT TRUNCATED AT 250 WORDS", "The amount of , and response of the kidneys to , endogenous natriuretic factor(s ) could be important in the pathogenesis of essential hypertension . Search ing for possible disturbance(s ) related to atrial natriuretic factor ( ANF ) and its second messenger , cyclic guanosine monophosphate ( c-GMP ) , we assessed plasma immunoreactive ( ir ) ANF and c-GMP , effective renal plasma flow ( ERPF ) , glomerular filtration rate ( GFR ) , urinary c-GMP , absolute and fractional ( FE ) excretions of sodium ( Na ) and chloride ( Cl ) before and during infusions of low ANF doses or vehicle ( V ) in 7 normotensive sons of essential hypertensive parents ( SEH ) compared with 7 sons of normotensive parents ( SN ) . Each subject was infused at 2-week intervals in a single-blind r and omized sequence with 4 different solutions : V only or ANF 0.004 , 0.008 and 0.016 microgram/kg/min , infused over 90 min . Plasma irANF was lower in SEH than in SN ( p Basal plasma c-GMP levels were , on all 4 different study days lower ( p Response of plasma c-GMP to infused ANF was also slightly decreased in SEH ( p BP , ERPF and GFR did not differ between SEH and SN and were unchanged during the 4 infusions . Urinary c-GMP excretion , FENa and FECl increased dose-dependently during ANF ( p < 0.05 to < 0.0001 ) but not V infusions . These findings indicate that at the stage of pre-hypertension a disturbance in the ANF-c-GMP regulatory pathway may occur , which is expressed primarily at the circulatory rather than the renal excretory level", "CONTEXT Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality , but the optimal first-step therapy is unknown . OBJECTIVE To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease ( CHD ) or other cardiovascular disease ( CVD ) events vs treatment with a diuretic . DESIGN The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) , a r and omized , double-blind , active-controlled clinical trial conducted from February 1994 through March 2002 . SETTING AND PARTICIPANTS A total of 33 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers . INTERVENTIONS Participants were r and omly assigned to receive chlorthalidone , 12.5 to 25 mg/d ( n = 15 255 ) ; amlodipine , 2.5 to 10 mg/d ( n = 9048 ) ; or lisinopril , 10 to 40 mg/d ( n = 9054 ) for planned follow-up of approximately 4 to 8 years . MAIN OUTCOME MEASURES The primary outcome was combined fatal CHD or nonfatal myocardial infa rct ion , analyzed by intent-to-treat . Secondary outcomes were all-cause mortality , stroke , combined CHD ( primary outcome , coronary revascularization , or angina with hospitalization ) , and combined CVD ( combined CHD , stroke , treated angina without hospitalization , heart failure [ HF ] , and peripheral arterial disease ) . RESULTS Mean follow-up was 4.9 years . The primary outcome occurred in 2956 participants , with no difference between treatments . Compared with chlorthalidone ( 6-year rate , 11.5 % ) , the relative risks ( RRs ) were 0.98 ( 95 % CI , 0.90 - 1.07 ) for amlodipine ( 6-year rate , 11.3 % ) and 0.99 ( 95 % CI , 0.91 - 1.08 ) for lisinopril ( 6-year rate , 11.4 % ) . Likewise , all-cause mortality did not differ between groups . Five-year systolic blood pressures were significantly higher in the amlodipine ( 0.8 mm Hg , P = .03 ) and lisinopril ( 2 mm Hg , P chlorthalidone , and 5-year diastolic blood pressure was significantly lower with amlodipine ( 0.8 mm Hg , P amlodipine vs chlorthalidone , secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine ( 10.2 % vs 7.7 % ; RR , 1.38 ; 95 % CI , 1.25 - 1.52 ) . For lisinopril vs chlorthalidone , lisinopril had higher 6-year rates of combined CVD ( 33.3 % vs 30.9 % ; RR , 1.10 ; 95 % CI , 1.05 - 1.16 ) ; stroke ( 6.3 % vs 5.6 % ; RR , 1.15 ; 95 % CI , 1.02 - 1.30 ) ; and HF ( 8.7 % vs 7.7 % ; RR , 1.19 ; 95 % CI , 1.07 - 1.31 ) . CONCLUSION Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive . They should be preferred for first-step antihypertensive therapy", "The antihypertensive effect of isradipine compared with placebo was assessed in 28 male patients ( aged 40–64 years ) with mild-to-moderate essential hypertension . After withdrawal of all previous antihypertensive treatment , these patients were entered into a 4-week placebo period followed by r and omization to receive double-blind , for 8 weeks , either placebo ( n = 14 ) or isradipine at 1.25–2.5 mg twice daily ( n = 14 ) . Twenty-four-hour ambulatory blood pressure was measured by Accutracker at the end of the placebo period and at the end of active treatment . In the isradipine group . both systolic and diastolic blood pressures decreased significantly ( p blood pressure increased in those taking placebo . In addition , isradipine as monotherapy con-trolled blood pressure throughout the day and night , and especially during the early morning , in these patients", "AIM To evaluate the effect of amlodipine on blood pressure and cerebral blood flow in elderly subjects with mild to moderate hypertension . METHODS A double-blind , parallel group study of 26 patients . After a 4-week placebo run-in period , amlodipine ( 5 - 10 mg ) or matching placebo was given once daily for 8 weeks . RESULTS Amlodipine significantly reduced blood pressure compared with baseline . Diastolic blood pressure was significantly reduced by amlodipine compared with placebo ( P Ambulatory blood pressure monitoring showed that blood pressure control was sustained over the 24-h dosing interval . Relative regional cerebral blood flow , assessed using single photon emission computed tomography , was not significantly affected by amlodipine . Three placebo patients , but no amlodipine patients , withdrew because of adverse events . CONCLUSION Amlodipine was a well-tolerated and effective antihypertensive agent , and did not reduce regional cerebral blood flow in elderly hypertensive patients", "OBJECTIVES : To compare the antihypertensive effects and duration of action of the angiotensin II receptor antagonist , telmisartan , amlodipine , and placebo in patients with mild-to-moderate hypertension using both conventional clinic blood pressures and ambulatory blood pressure monitoring ( ABPM ) . METHODS : After a 4-week single-blind , placebo run-in period , qualifying patients were r and omly allocated in double-blind manner to be administered 40 mg telmisartan ( n = 73 ; increased to 80 and 120 mg as necessary for patients whose diastolic blood pressure ( DBP ) remained > 90 mmHg ) ; 5 mg amlodipine ( n = 78 ; titrated to 5 mg and titrated to 10 mg for patients whose DBP remained > 90 mmHg ) ; or placebo ( n = 81 ) . ABPM was performed at the end of the baseline period and again at the end of 12 weeks of double-blind treatment . RESULTS : Telmisartan and amlodipine treatments significantly decreased trough supine systolic blood pressure and DBP ( P placebo . Both drugs also significantly reduced 24 h mean systolic blood pressures and DBP compared with placebo ( P Reductions in DBP with telmisartan were greater ( P amlodipine during the night-time interval and the last 4 h of the dosing period . Twenty-four-hour mean ABPM DBP telmisartan patients and in 55 % of patients administered amlodipine . In addition , heart rates in patients treated with telmisartan were lower than heart rates in those treated with amlodipine during the final 4 h of the dosing period ( P = 0.0003 ) and during the morning interval ( P = 0.005 ) . Generally , both telmisartan and amlodipine were well tolerated , however , drug-related edema occurred significantly more commonly ( P amlodipine than it did among patients administered either telmisartan or placebo . CONCLUSIONS : Clinic blood pressure measurements detected no difference between the antihypertensive effects and duration s of action of telmisartan and amlodipine , both agents producing statistically significant reductions compared with placebo . ABPM measurements , however , revealed differences between the efficacies at specific time points within the dosing periods . These findings highlight the potential importance of the use of ABPM for evaluating and comparing efficacies of antihypertensive agents", "AIM To evaluate the antihypertensive efficacy of nifedipine gastrointestinal therapeutic system ( GITS ) , a slow-release formulation of nifedipine . PATIENTS AND METHODS A r and omly allocated , double-blind , placebo-controlled trial was set up with 126 essential hypertensives who were assessed by ambulatory blood pressure monitoring . A 2-week placebo run-in phase was followed by treatment with nifedipine GITS at 30 mg ( n = 42 ) or 60 mg ( n = 42 ) or with a placebo ( n = 42 ) once a day for 4 weeks . At the end of each period , 24- to 36-h ambulatory blood pressure was measured at 15-min intervals by a SpaceLabs 90202 or 90207 device . The peak effect of nifedipine was assessed as the lowest average hourly value of systolic/diastolic blood pressure 2 - 6 h after drug intake subtracted from the baseline value for the same hour , and the trough effect as the mean systolic/diastolic blood pressure obtained 24 h after the dose subtracted from the baseline value for the same hour . RESULTS In the 81 patients with 24-h valid ambulatory blood pressure data , 24-h , daytime and night-time mean systolic and diastolic blood pressures were significantly decreased by nifedipine GITS at both doses , but were not changed by the placebo . The trough : peak ratios for systolic and diastolic blood pressure were 90.5 and 76.3 % for 30 mg nifedipine GITS and 109.3 and 98.6 % for 60 mg nifedipine GITS . Correction by trough and peak effects in the placebo group further increased the trough : peak ratios . In 51 patients with 36-h ambulatory blood pressure data , trough : peak ratios above the United States Food and Drug Administration recommended value of 50 % were found 30 h after the dose , and systolic blood pressure was still significantly lower 36 h after the nifedipine GITS dose", "Data from 2 separate multicenter , double-blind clinical studies following the same protocol , except for the selection of doses , were pooled to evaluate the efficacy and tolerability of fixed doses of a new sustained-release ( SR ) formulation of nifedipine compared with placebo in 388 patients with mild to moderate uncomplicated essential hypertension . After a 3 - 6 week placebo washout period , the patients were r and omized to receive either placebo or nifedipine SR-20 mg ( study I only ) , 50 mg , 100 mg , or 150 mg ( study II only ) . Among the 278 patients who completed 6 weeks of active therapy , mean supine diastolic blood pressure reductions from pretreatment baseline were 5.9 , 9.3 , 9.2 , 11.1 , and 13.2 mm Hg in the placebo , 20- , 50- , 100- , and 150-mg groups , respectively . The reductions achieved in each of the nifedipine SR groups were statistically significant versus baseline values ( p less than 0.001 ) . All nifedipine-SR doses reduced supine systolic blood pressure significantly more than placebo ( p less than 0.001 ) . In addition , there was a significant linear relationship between the log of the dose and the blood pressure reduction ( p less than 0.05 ) . Automated ambulatory blood pressure recordings performed in 221 of the patients showed that the blood pressure was lowered evenly through the entire 24-hour dosing period . The doses that were effective and associated with the fewest adverse reactions were 20 mg and 50 mg once daily", "This multicenter , double-masked , r and omized , parallel-group study compared the efficacy , tolerability , and safety of amlodipine 5 mg/benazepril 20 mg , amlodipine 5 mg , benazepril 20 mg , and placebo in patients with essential hypertension . After a placebo run-in period , 308 patients ( all white ) were r and omized to treatment groups and took medication once daily for 8 weeks . Blood pressure was measured after 4 and 8 weeks of treatment in the 23- to 26-hour period after dosing . Patients wore a noninvasive blood pressure monitor for 24 hours before r and omization and before the final visit . Investigators recorded adverse experiences at r and omization and at study weeks 4 and 8 , and obtained specimens for laboratory testing at r and omization and at study week 8 . Three hundred seven patients were evaluated for efficacy , and 308 for tolerability and safety . At end point ( the last postr and omization measurement for each patient ) , the reduction in mean sitting diastolic blood pressure with the amlodipine 5 mg/benazepril 20 mg treatment was statistically significantly greater than with any comparative therapy . The results of 24-hour monitoring showed that the amlodipine/benazepril treatment , unlike monotherapy , maintained the hourly mean diastolic blood pressure at responder rate of 87.0 % was observed with amlodipine 5 mg/benazepril 20 mg versus 67.5 % , 53.3 % , and 15.8 % with amlodipine , benazepril , and placebo , respectively . This difference between the amlodipine/benazepril treatment group and each comparative single-agent treatment group was statistically significant . Drug-related adverse events occurred in 15.6 % of patients in the amlodipine/benazepril group and in 24.7 % , 6.5 % , and 11.7 % of patients in the amlodipine , benazepril , and placebo groups , respectively . Edema occurred less often in the amlodipine/benazepril group than in the amlodipine group . Overall , once-daily therapy with amlodipine 5 mg/benazepril 20 mg provided an antihypertensive effect that was statistically and clinical ly superior to amlodipine 5 mg alone , benazepril 20 mg alone , and placebo , was well tolerated , and was associated with less edema than the amlodipine treatment", "The effects of amlodipine on ambulatory blood pressure were investigated in patients with mild-to-moderate hypertension . Ambulatory recordings showed that amlodipine maintained diastolic and systolic blood pressure below baseline levels for a full 24-h period without altering the normal circadian rhythm . No reflex tachycardia occurred and side effects were rare", "Summary : Arterial effects evaluated by carotid-femoral , brachial-radial , and femoral-tibial pulse wave velocity and antihypertensive effect evaluated by 24-h ambulatory blood pressure ( BP ) monitoring were measured in 17 hypertensive patients before and 24 h after once-daily nitrendipine ( 20 mg ) administration . After a 15-day placebo period , a double-blind study of nitrendipine versus placebo was performed for 1 month . After nitrendipine dosing , BP measured by sphygmomanometer 24 h after the last drug intake showed a significant decrease as compared with the pretreatment period . Ambulatory BP mean values were also significantly decreased for systolic and diastolic BP ( SBP , DBP ) . This decrease predominated during the day but was observed nocturnally only after 6 a.m. Twenty-four hours after the last tablet intake of nitrendipine , carotid-femoral and brachial-radial pulse wave velocities were significantly reduced , whereas femoral-tibial wave velocity was unchanged , indicating that markers of arterial rigidity might be substantially modified and that the modifications were partly unrelated to BP changes . The results provide evidence that in hypertensive subjects nitrendipine 20 mg given once daily for 1 month produces an arterial effect for 24 h , in association with BP reduction" ]	41188876-06ff-11f0-808a-c43d1ab1c353
Background and Purpose — Patients with a transient ischemic attack or ischemic stroke have an increased risk of subsequent cardiovascular events . The purpose of this systematic review and meta- analysis was to determine whether lifestyle interventions focusing on behaviorally modifiable risk factors with or without an exercise program are effective in terms of ( 1 ) preventing recurrent cardiovascular events , ( 2 ) reducing mortality , and ( 3 ) improving modifiable risk factors associated with cardiovascular disease in patients after a transient ischemic attack or ischemic stroke . Methods — For this systematic review and meta- analysis , we systematic ally search ed PubMed , Embase , PsycInfo , and the Cochrane Library from the start of the data base to May 7 , 2015 . Subgroup analyses were conducted to explore the influence of therapy-related factors . Results — Twenty-two r and omized controlled trials were identified with a total of 2574 patients . Pooling showed a significant reduction in systolic blood pressure by the lifestyle interventions applied , compared with usual care ( mean difference , −3.6 mm Hg ; 95 % confidence interval , −5.6 to −1.6 , I2=33 % ) . No significant effect was found on cardiovascular events , mortality , diastolic blood pressure , or cholesterol . In the subgroup analyses , the trials with cardiovascular fitness interventions , trials with an intervention that lasted longer than 4 months , and interventions that used > 3 behavior change techniques were more effective in reducing systolic blood pressure . Conclusions — We found that lifestyle interventions are effective in lowering systolic blood pressure . About other end points , this systematic review found no effect of lifestyle interventions on cardiovascular event rate mortality , diastolic blood pressure , or total cholesterol	[ "Objective : Despite evidence demonstrating that risk-factor management is effective in reducing recurrent cerebrovascular disease , there are very few structured care programmes for stroke survivors . The aim was to implement and evaluate an integrated care programme in stroke . Methods : 186 patients with stroke were r and omised to either the treatment ( integrated care ) or control ( usual care ) group and were followed up over 12 months . The Integrated Care for the Reduction of Secondary Stroke ( ICARUSS ) model of integrated care involved collaboration between a specialist stroke service , a hospital coordinator and a patient ’s general practitioner . The primary aim was to promote the management of vascular risk factors through ongoing patient contact and education . Results : In the 12 months poststroke , systolic blood pressure ( sBP ) decreased in the treatment group but increased in controls . The group difference was significant , and remained so when age , sex , disability and sBP at discharge were accounted for ( p = 0.04 ) . Treatment patients also exhibited better modification of body mass index ( p = 0.007 ) and number of walks taken ( p controls . Rankin scores indicated significantly reduced disability in treatment patients relative to controls in the year poststroke ( p = 0.003 ) . Conclusions : Through an integrated system of education , advice and support to both patient and GP , the ICARUSS model was effective in modifying a variety of vascular risk factors and therefore should decrease the likelihood or recurrent stroke or vascular event", "Objectives To investigate if repeated verbal instructions about physical activity to patients with ischaemic stroke could increase long term physical activity . Design Multicentre , multinational , r and omised clinical trial with masked outcome assessment . Setting Stroke units in Denmark , China , Pol and , and Estonia . Participants 314 patients with ischaemic stroke aged ≥40 years who were able to walk—157 ( mean age 69.7 years ) r and omised to the intervention , 157 ( mean age 69.4 years ) in the control group . Interventions Patients r and omised to the intervention were instructed in a detailed training programme before discharge and at five follow-up visits during 24 months . Control patients had follow-up visits with the same frequency but without instructions in physical activity . Main outcome measures Physical activity assessed with the Physical Activity Scale for the Elderly ( PASE ) at each visit . Secondary outcomes were clinical events . Results The estimated mean PASE scores were 69.1 in the intervention group and 64.0 in the control group ( difference 5.0 ( 95 % confidence interval −5.8 to 15.9 ) , P=0.36 . The intervention had no significant effect on mortality , recurrent stroke , myocardial infa rct ion , or falls and fractures . Conclusion Repeated encouragement and verbal instruction in being physically active did not lead to a significant increase in physical activity measured by the PASE score . More intensive strategies seem to be needed to promote physical activity after ischaemic stroke . Trial registration Clinical Trials", "The effectiveness of methods to prevent stroke recurrence and of education focusing on learners ' needs has not been fully explored . The aims of this study were to assess the effects of such interventions among stroke patients and their primary caregivers and to evaluate the feasibility of a web-based stroke education program . The participants were 36 patients with a clinical diagnosis of ischemic stroke within 12 months post-stroke and their primary caregivers . The participants were r and omly assigned to either an experimental or a control group . The primary measures included blood chemistry , self-reported health behaviors , sense of control , and health motivation for stroke patients , and caregiver mastery for caregivers . To test the feasibility of the intervention program , the rates of participation and occurrence of technical problems were calculated . The experimental group tended to improve significantly more than the control group in terms of exercise , diet , sense of control and health motivation for the stroke patients and in terms of caregiver mastery for the primary caregivers . The rate of participation in the web-based program was 63.1 % . This program , which focuses on recurrence prevention in stroke patients and caregivers , has the potential to improve health behaviors for stroke patients", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "OBJECTIVE To examine the feasibility , safety and effectiveness of an early aerobic rehabilitation program for patients after minor ischemic stroke . DESIGN R and omized control trial . METHODS Twenty-eight patients , 1 - 3 weeks post minor ischemic stroke ( modified Rankin scale ; mRS ≤ 2 ) , were r and omly assigned to intervention or control groups . Measures were taken at weeks 1 and 6 . All participants were instructed in home practice to achieve strength and flexibility , and were asked to continue their normal community routine . Intervention group participants performed a supervised exercise training program twice a week for 6 weeks . Exercise capacity was evaluated by the 6-minute walk distance test ( 6MWD ) , and the modified Bruce treadmill test . RESULTS Eight subjects out of 14 participated in all 12 training sessions , one at less than 50 % of the sessions , while five reached the highest stage of the program . No adverse events were noted during the intervention period . In the intention to treat analysis a significant improvement over time was seen for the functional parameters only . No interaction ( group*time ) was found . According to the per protocol analysis a significant interaction effect was found ; only the intervention group participants showed a significant clinical change in the 6MWD test ( 412 ± 178 meters to 472 ± 196 meters , vs the control group 459 ± 116 meters to 484 ± 122 meters , p An early supervised aerobic training after minor ischemic stroke is feasible and well tolerated and , in a per- protocol analysis , was associated with improved walking endurance . Further studies with a larger sample size are needed to assess the effect of such a program on functional abilities , prevention of risk factors , and recurrent stroke", "Objective : To evaluate the effectiveness of lifestyle group intervention on well-being , occupation and social participation . Design : A r and omized controlled trial . Setting : Senior centres in the community . Subjects : Of 204 stroke survivors screened , 99 ( 49 % ) were r and omized three months after stroke whereby 86 ( 87 % ) participants ( mean ( SD ) age 77.0 ( 7.1 ) years ) completed all assessment s ( 39 in the intervention group and 47 in the control group ) . Intervention : A lifestyle course in combination with physical activity ( intervention group ) compared with physical activity alone ( control group ) . Both programmes were held once a week for nine months . Main outcome measure : The Short Form Question naire ( SF-36 ) , addressing well-being and social participation . Assessment s were performed at baseline and at nine months follow-up . Results : We found no statistically significant differences between the groups at the nine months follow-up in the SF-36 . Adjusted mean differences in change scores in the eight subscales of SF-36 were ; ‘ mental health ’ ( + 1.8 , 95 % confidence interval ( CI ) –4.0 , + 7.6 ) , ‘ vitality ’ ( −3.0 , 95 % CI −9.6 , + 3.6 ) , ‘ bodily pain ’ ( + 3.3 , 95 % CI −7.8 , + 14.4 ) , ‘ general health ’ ( −1.6 , 95 % CI −8.4 , + 5.1 ) , ‘ social functioning ’ ( −2.5 , 95 % CI −12.8 , + 7.8 ) , ‘ physical functioning ’ ( + 1.0 , 95 % CI −6.7 , + 8.6 ) , ‘ role physical ’ ( −7.1 , 95 % CI −22.7 , + 8.4 ) , ‘ role emotional ’ ( + 11.8 , 95 % CI −4.4 , + 28.0 ) . Conclusions : Improvements were seen in both groups , but no statistically significant differences were found in the intervention group compared to controls . An intervention comprising regular group-based activity with peers may be sufficient in the long-term rehabilitation after stroke", "BACKGROUND Current guidelines recommend global risk assessment to guide vascular risk factor management ; however , most provider-patient communication focuses on individual risk factors in isolation . We sought to evaluate the impact of personalized coronary heart disease and stroke risk communication on patients ' knowledge , beliefs , and health behavior . METHODS We conducted a r and omized controlled trial testing personalized risk communication based on Framingham stroke and coronary heart disease risk scores compared with a st and ard risk factor education . A total of 89 patients were recruited from primary care clinics and followed up for 3 months . Outcomes included the following : risk perception and worry , risk factor knowledge , risk reduction preferences and decision conflict , medication adherence , health behaviors , and blood pressure . RESULTS Participants had a very low underst and ing of numeric information , high perceived risk for stroke or myocardial infa rct ion , and high proportion of medication nonadherence . Patients ' ability to identify vascular risk factors increased with personalized risk communication ( mean 1.8 additional risk factors , 95 % CI 1.3 - 2.2 ) and st and ard risk factor education ( mean 1.6 additional risk factors , 95 % CI 1.1 - 2.1 ) immediately after the intervention but was not sustained at 3 months . Patients in the personalized group had less decision conflict than the st and ard risk factor education group over intended risk reduction strategies ( 5.9 vs 10.1 , P = .003 ) . There was no appreciable impact of either communication strategy on medication adherence , exercise , smoking cessation , or blood pressure . CONCLUSIONS Personalized risk communication was preferred by patients and had a small impact on risk reduction preferences and decision conflict but had no impact on patient beliefs or behavior compared with st and ard risk factor education", "Objective : To evaluate risk factor reduction and health-related quality of life following a 10-week cardiac rehabilitation programme in non-acute ischaemic stroke subjects . Design : Single-blinded r and omized control trial . Setting : Outpatient rehabilitation . Subjects : Forty-eight community-dwelling ischaemic stroke patients ( 38 independently mobile , 9 requiring assistance , 1 non-ambulatory ) were r and omly assigned to intervention or control groups by concealed allocation . Intervention : The trial consisted of a 10-week schedule with measures taken at weeks 1 and 10 . Both groups continued usual care ( excluding aerobic exercise ) ; intervention subjects attended 16 cycle ergometry sessions of aerobic-training intensity and two stress-management classes . Main outcome measures : Cardiac risk score ( CRS ) ; VO2 ( mL O2/kg per minute ) and Borg Rate of Perceived Exertion ( RPE ) assessed during a st and ardized ergometry test ; Hospital Anxiety and Depression Scale ( HADS ) ; Frenchay Activity Index ; Fasting Lipid Profiles and Resting Blood Pressure . Results : Group comparison with independent t-tests showed significantly greater improvement at follow-up by intervention subjects than controls in VO2 ( intervention 10.6 ±1.6 to 12.0 ± 2.2 , control 11.1 ±1.8 to 11.1 ±1.9 t=4.734 , P CRS ( intervention 13.4 ±10.1 to 12.4 ±10.5 , control 9.4 ±6.7 to 15.0 ±6.1 t=-2.537 , P RPE rating decreased in intervention subjects ( 13.4 ±12.2 to 12.4 ±2.0 ) and increased in controls ( 13.8 ±1.8 to 14.4 ±1.6 ) ; Mann — Whitney U ( U = 173.5 , P the HADS depression subscale in the intervention group alone ( 5.1 ±3.4 to 3.0 ±2.8 ) ( Wilcoxon signed ranks test Z=-3.278 , P non-acute ischaemic stroke patients can improve their cardiovascular fitness and reduce their CRS with a cardiac rehabilitation programme . The intervention was associated with improvement in self-reported depression ", "The aim was to study if health outcome and secondary prevention were satisfactory 1 year after stroke and if nurse-led interventions 3 months after stroke could have impact . Design was a r and omized controlled open trial in a 1-year population . Primary outcome was health status 1 year after stroke . One month after stroke , survivors were r and omized into intervention group ( IG ) with follow-up by a specialist nurse ( SN ) after 3 months ( n = 232 ) , and control group ( CG ) with st and ard care ( n = 227 ) , all to be followed up 1 year after stroke . At the first follow-up , patients grade d their health , replied to the EuroQol-5 Dimensions ( EQ-5D ) health outcome questions , health problems were assessed , and supportive counseling was provided in the IG . Health problems requiring medical interventions were primarily referred to a general practitioner ( GP ) . One year after stroke , 391 survivors were followed up . Systolic blood pressure ( BP ) had decreased in IG ( n = 194 ) from median 140 to 135 ( P = .05 ) , but about half were above the limit 139 in both groups . A larger proportion ( 22 % ) had systolic BP > 155 in the CG ( n = 197 ) than in the IG ( 14 % ; P = .05 ) . In the IG , 62 % needed referrals compared with the 75 % in the CG ( P = .009 ) . Forty percent in the IG and 52.5 % in the CG ( P = .04 ) reported anxiety/depression . In the IG , 75 % and 67 % in the CG rated their general health as fairly good or very good ( P = .05 ) . Although nurse-led interventions could have some effect , the results were not optimal . A more powerful strategy could be closer collaboration between the SN and a stroke clinician , before referring to primary care", "Objective : Little is known about the long-term effectiveness after stroke of interventions for behaviour modification and ensuring concordance with therapies . We describe a follow-up study of a previous r and omized controlled trial of a brief period of behaviour modification . The aim of this study was to determine outcomes three years after the initial intervention . Design : Survivors of the original cohort were contacted and asked to attend for follow-up interview , within a geriatric day hospital . This study was carried out in the Geriatric Day Hospital at Stobhill Hospital , Balornock Road , Glasgow . Interventions : Details of risk factor control , including blood pressure , cholesterol levels and diabetic control , were assessed . Question naires used in the initial study were repeated including the Geriatric Depression Scale score , Euroqol Perceived Health Status and Stroke Services Satisfaction Question naire . Main measures : Primary outcome was collective risk factor control . Clinical outcomes including recurrent cerebrovascular events , medication persistence and perceived health status were also recorded . Results : Mean length of follow-up was 3.6 years ( SD 0.43 ) . Of the 205 patients enrolled in the initial study , 102 patients attended for repeat interview ( 49 intervention/53 control ) . There were no significant differences in the percentage of controlled risk factors between groups ( intervention 51.7 % versus control 55.9 % , P = 0.53 ) . Similarities were observed in the number of recurrent clinical events and medication persistence between groups . No overall difference was observed in perceived health status , satisfaction with care or depression scores . Conclusions : Brief intervention with respect to behaviour modification and risk factor control does not appear to have any long-term benefit . These results must be cautiously interpreted in light of the small study number and further research is required", "Objective : To evaluate the feasibility and effectiveness of a st and ard National Health Service cardiac rehabilitation programme on risk factor reduction for patients after a minor stroke and transient ischaemic attack . Design : Single-blind r and omized controlled trial . Setting : Cardiac rehabilitation classes . Subjects : Twenty-four patients . Intervention : All participants received st and ard care . In addition , the intervention group undertook an eight-week cardiac rehabilitation programme consisting of weekly exercise and education classes . Outcome measures : Cardiovascular disease risk score ; lipid profiles ; resting blood pressure ; C-reactive protein ( measured with a high sensitive assay ) and fibrinogen levels ; blood glucose ; obesity ; physical activity levels ; subjective health status ( SF-36 ) ; Hospital Anxiety and Depression Scale . Results : Group comparison with independent t-tests showed a significantly greater improvement in the cardiovascular disease risk score for participants in the intervention group compared to st and ard care ( intervention 25.7 ± 22.8 to 23.15 ± 18.3 , control 25.03 ± 15.4 to 27.12 ± 16.1 , t = −1.81 , P in activity levels ( intervention 9.41 ± 7.7 to 8.08 ± 5.7 , control 14.50 ± 5.5 to 9.83 ± 6.6 , t = −2.00 , P 0.05 ) and the SF-36 domains of physical functioning ( intervention 70 ± 24.6 to 75.4 ± 11.1 , control 90.00 ± 12.4 to 83.16 ± 17.3 , t = −2.72 , P 0.05 ) and mental health ( intervention 84 ± 40 to 92 ± 40 , control 88.00 ± 60 to 84 ± 44 , z = −2.06 , P suggest that st and ard cardiac rehabilitation programmes are a feasible and effective means of reducing the risk of future cardiovascular events for patients after minor stroke and transient ischaemic attack", "BACKGROUND This r and omized controlled trial tested the effectiveness of comprehensive , interdisciplinary postdischarge care management in improving a profile of indicators of health recovery and secondary prevention ( profile of health and prevention ) in stroke and transient ischemic attack ( TIA ) patients . METHODS Ninety-six stroke/TIA patients were r and omized to usual care or intervention at discharge from our acute stroke unit . The intervention group received an in-home biopsychosocial assessment by an advanced practice nurse at 1 month . A care plan was developed by an interdisciplinary team and implemented in collaboration with the patient 's primary care physician . The profile of health and prevention , measured at 3 months , was comprised of 5 domains : ( 1 ) Neuromotor Function , ( 2 ) Severe Complications , ( 3 ) Quality of Life , ( 4 ) Management of Risk for common poststroke complications and recurrent stroke , and ( 5 ) Stroke Knowledge . A single global hypothesis test across multiple end points was used to compare the 2 groups . RESULTS The intervention significantly improved the profile of health and prevention ( P Effect sizes ( in st and ard deviation units ) of the intervention on domains were .1 for Neuromotor Function ( 90 % confidence interval [ CI ] = -.3 to .5 ) ; .4 for Severe Complications ( 90 % CI = .1 to .8 ) ; .5 for Quality of Life ( 90 % CI = .1 to .9 ) ; .6 for Management of Risk for common poststroke complications and recurrent stroke ( 90 % CI = .3 to 1 . ) ; and 1.0 for Stroke Knowledge ( 90 % CI = .6 to 1.4 ) . CONCLUSIONS This model of care management result ed in a significantly better profile of health and prevention for stroke/TIA patients 3 months postdischarge", "OBJECTIVES To compare the effects of 3 different exercise training regimens on cardiorespiratory fitness and coronary risk factor reduction in subjects with unilateral stroke . DESIGN A cluster assignment by residential location repeated- measures design . SETTING University-based medical center . PARTICIPANTS Fifty-five subjects with unilateral ischemic stroke were assigned to the following groups : intensity ( n=18 ) , duration ( n=19 ) , and therapeutic exercise ( n=18 ) . INTERVENTION A 14-week intervention with subjects r and omized to 1 of 3 interventions : ( 1 ) moderate intensity , shorter duration ( MISD ) exercise ( gradually increasing exercise intensity while keeping exercise duration constant at 30 min ) , ( 2 ) low-intensity , longer duration ( LILD ) exercise ( gradually increasing duration to 60 min while keeping exercise intensity constant ) , or ( 3 ) conventional therapeutic exercise ( TE ) consisting mainly of strength , balance , and range of motion activities . All groups exercised 3 days per week . MAIN OUTCOME MEASURES Peak oxygen consumption ( VO2peak ) , submaximal oxygen consumption ( VO2 ) , lipid panel , and resting blood pressure . RESULTS The MISD group attained more favorable effects on systolic ( P ) and diastolic blood pressure ( P and total cholesterol ( TC ) ( P MISD ( P triglycerides compared with TE ( P VO2peak and submaximal VO2 in any of the groups . CONCLUSIONS Overall , both MISD and LILD conditions achieved greater clinical and significant gains in coronary risk reduction compared with TE", "Objective : To evaluate whether enhanced secondary prevention more significantly influences readiness to change health behaviour after minor stroke/transient ischaemic attack , compared with conventional stroke secondary prevention . Design : Single-blind r and omized control trial . Setting : Rural district general hospital outpatient clinic . Subjects : Fifteen women and 37 men with a mean age of 68.3 years with first minor stroke or transient ischaemic attack . Interventions : The intervention group received ‘ enhanced secondary prevention ’ ( additional advice , motivational interviewing and telephone support ) to change health behaviour . Both groups received ‘ conventional care ’ which included advice given during routine care . Main measures : The primary outcome was ‘ readiness to change behaviour ’ measured using a vali date d stroke specific score based on the transtheoretical model . Secondary outcomes were the Hospital Anxiety and Depression Scale , and self-reported alcohol consumption , smoking behaviour , exercise frequency , and fruit and vegetable consumption . Results : Analysis of the data for the 52 participants showed no statistical difference in the groups for the primary outcome of readiness to change behaviour . Statistically significant improvements for change in self-reported exercise were demonstrated ( P = 0.007 ) ; to 2—3 times per week in the intervention group compared to 0—1 times per week in the control group , and in fruit and vegetable consumption ( P = 0.033 ) ; to 10 portions of fruit and vegetables consumed per week in the intervention group compared to 1 or 2 portions a week for the control group . No evidence of a difference between groups was seen for alcohol consumption or Hospital Anxiety and Depression Scale . Conclusions : While no difference was demonstrated between the groups for readiness to change behaviour , a clinical ly significant effect in reported exercise behaviour and diet were demonstrated in the intervention group . This interesting finding indicates a dissonance between the behaviour scale and actual behaviour change , potentially indicating a lack of sensitivity of the scale to detect a change in this patient group", "Lowering blood pressure ( BP ) in stroke survivors reduces the risk of recurrent stroke . We tested the hypothesis that a nurse-led nonpharmacologic intervention would lower the BP of participants in an intervention group compared with a control group . A total of 349 patients who had sustained acute stroke or transient ischemic attack were r and omly assigned to either usual care or to 4 home visits by a nurse . During the visits , the nurse measured and recorded BP and provided individually tailored counseling on a healthy lifestyle . A total of 303 patients completed the 1-year follow up . No change in systolic BP was noted in either the intervention group or the control group . Because of an increase in diastolic BP in the control group ( P = .03 ) , a difference in mean diastolic BP between the 2 groups was found at follow-up ( P = .007 ) . Mean BP at follow-up was 139/82 mm Hg in the intervention group and 142/86 mm Hg in the control group . Linear regression analysis demonstrated that BP at the point of discharge was the strongest predictor of BP 1 year later ( P proportion of patients on antihypertensive medication increased in the intervention group ( P = .002 ) . Patients were compliant with antihypertensive therapy , and 92 % of the hypertensive patients in the intervention group followed the advice to see a general practitioner ( GP ) for BP checkups . At follow-up , 187 patients ( 62 % ) were hypertensive , with no difference in the rate of hypertension seen between the groups . Our data indicate that home visits by nurses did not result in a lowering of BP . Patients complied with antihypertensive therapy and GP visits in the case of hypertension . Nonetheless , the majority of patients were hypertensive at the 1-year follow up", "Background : Lifestyle modification is associated with a substantially decreased risk of cardiovascular events . However , the role of lifestyle intervention for secondary prevention in patients with noncardioembolic ischemic stroke is inadequately defined . We assessed the hypothesis that lifestyle intervention can reduce the onset of new vascular events in patients with noncardioembolic mild ischemic stroke . Methods : We conducted an observer-blind r and omized controlled trial that enrolled 70 patients ( 48 men , mean age 63.5 years ) with acute noncardioembolic mild ischemic stroke . The patients were allocated in equal numbers to a lifestyle intervention group or a control group . We performed lifestyle interventions , which comprised exercise training , salt restriction and nutrition advice for 24 weeks . Then all patients were prospect ively followed up for occurrence of the primary endpoints , including hospitalization due to stroke recurrence and the onset of other vascular events . We also evaluated systolic blood pressure ( SBP ) at the clinic and at home , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , hemoglobin A1c ( HbA1c ) and high-sensitivity C-reactive protein ( hs-CRP ) to compare the efficacy of the lifestyle interventions . Results : This trial was terminated earlier than expected because of the prespecified early stopping rule for efficacy . After the 24-week intervention period , the intervention group showed a significant increase in daily physical activity and a significant decrease in salt intake ( physical activity , p = 0.012 ; salt intake , p blood pressure was decreased and the HDL-C levels were increased in the intervention group ( SBP , p LDL-C , HbA1c and hs-CRP tended to decrease in the intervention group , but this decrease did not achieve significance . After a median follow-up period of 2.9 years , 12 patients allocated to the control group and 1 patient in the lifestyle intervention group experienced at least 1 vascular event . A sequential plans analysis indicated the superiority of the lifestyle intervention in interim analysis . Kaplan-Meier survival curves after the log-rank test showed a significant prognostic difference between the r and omized groups ( p = 0.005 ) . Conclusions : Lifestyle intervention with appropriate medication is beneficial for reducing the incidence of new vascular events and improving vascular risk factors in patients with noncardioembolic mild ischemic stroke", "OBJECTIVES To determine whether a practice effect occurs across 2 trials of the six-minute walk test ( 6MWT ) among community-dwelling people within 1 year poststroke and to identify characteristics distinguishing people who show a practice effect from those who do not . DESIGN Secondary analysis of scores on 2 trials of the 6MWT administered approximately 30 minutes apart at baseline in a r and omized controlled trial . SETTING General community . PARTICIPANTS People ( N=91 ) living in the community with a residual walking deficit within the first year of a first or recurrent stroke . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURE Distance walked on the 6MWT . RESULTS Mean 6MWT scores + /- SD for trials 1 and 2 were 196+/-119 m and 197+/-126 m , respectively ( n=83 ) . The mean difference in 6MWT performance across trials was 0+/-35 m ( 95 % confidence interval [ CI ] , -7 to 8 m ) . The Pearson correlation coefficient between 6MWT distances was .96 ( P 6MWT in individuals within 1 year poststroke . Thus , a practice walk does not appear necessary . Further research is recommended to evaluate the influence of young age , acute stroke , and mild-to-moderate gait deficit on practice effects", "ABSTRACT Secondary stroke prevention is championed as guideline care ; yet there are no systematic programs offered . We developed a stroke self-management program to address this gap and pilot test the program . We conducted a r and omized controlled trial at two Veterans Administration ( VA ) hospital sites where we recruited patients with an acute stroke to receive either the stroke program or an attention-control protocol over a 12-week period following hospital discharge . The stroke program included six sessions that facilitated stroke self management focusing on increasing self-efficacy to recover from stroke and engage in secondary stroke risk factor management . We surveyed outcomes at baseline , 3 and 6 months . We conducted an intention to treat analysis comparing the intervention to the control group on changes of outcomes between baseline and follow-up modeled by a linear model with fixed effects for treatment , visit , and the treatment by visit interaction adjusting for baseline . We recruited 63 participants ( 33 control and 30 intervention ) who were hospitalized with a primary diagnosis of ischemic stroke . We found trends in differences between groups on self-efficacy to communicate with physicians , weekly minutes spent in aerobic exercise , and on dimensions of stroke-specific quality of life . This pilot study demonstrated the feasibility of delivering a stroke self-management program to recent stroke survivors in a healthcare organization . The program also demonstrated improvements in patient self-efficacy , self-management behaviors , specific dimensions of stroke-specific quality of life compared to a group that received an attention placebo program", "OBJECTIVE We sought to evaluate whether comprehensive postdischarge care management for stroke survivors is superior to organized acute stroke department care with enhanced discharge planning in improving a profile of health and well-being . METHODS This was a r and omized trial of a comprehensive postdischarge care management intervention for patients with ischemic stroke and National Institutes of Health Stroke Scale scores greater than or equal to 1 discharged from an acute stroke department . An advanced practice nurse performed an in-home assessment for the intervention group from which an interdisciplinary team developed patient-specific care plans . The advanced practice nurse worked with the primary care physician and patient to implement the plan during the next 6 months . The intervention and usual care groups were compared using a global and closed hypothesis testing strategy . Outcomes fell into 5 domains : ( 1 ) neuromotor function , ( 2 ) institution time or death , ( 3 ) quality of life , ( 4 ) management of risk , and ( 5 ) stroke knowledge and lifestyle . RESULTS Treatment effect was near 0 SD for all except the stroke knowledge and lifestyle domain , which showed a significant effect of the intervention ( P = .0003 ) . CONCLUSIONS Postdischarge care management was not more effective than organized stroke department care with enhanced discharge planning in most domains in this population . The intervention did , however , fill a postdischarge knowledge gap", "The objective of this study was to conduct a r and omized , parallel-group clinical trial assessed the efficacy of a health-enhancing physical activity program ( exercise and education ) on vascular risk factors and aerobic fitness in patients who have experienced a transient ischemic attack ( TIA ) or nondisabling stroke . Sixty patients ( 69±11 years ) completed a baseline ( BL ) vascular risk stratification and aerobic fitness examination ( cycle test ) within 2 weeks of symptom onset . Subjects were then r and omized to either an 8-week , twice weekly exercise program or to a usual-care control ( CON ) group . Postintervention ( PI ) assessment s were completed immediately after the intervention and at 3-month follow-up . A series of primary ( systolic blood pressure [ SBP ] ) and secondary ( vascular risk factors like total cholesterol [ TC ] , high-density lipoproteins , etc . ; Framingham risk score ; peak oxygen uptake ) outcome measures were assessed . Significantly greater reductions in SBP ( mean change±SD ; -10.4±9.2 mm Hg ) and TC ( -.53±.90 mmol/L ) were observed between BL and PI assessment s for the exercise group compared with the CON group ( -1.9±15.4 mm Hg and -.08±.59 mmol/L , respectively ) ( P.05 ) . Significant improvements in aerobic fitness were also observed and maintained at the 3-month follow-up assessment after regular exercise participation ( P in exercise result ed in significant improvements in vascular risk factors and fitness in those diagnosed with TIA . As these beneficial effects were maintained up to 3 months after completing the exercise program , exercise should be considered a useful additive treatment strategy for newly diagnosed TIA patients . Future research should examine the long-term efficacy of such programs", "OBJECTIVE To evaluate exercise capacity of patients with a poststroke interval of less than 1 month . DESIGN Prospect i ve , cohort , observational study . SETTING Exercise testing laboratory in a tertiary care hospital . PARTICIPANTS Twenty-nine patients ( mean age + /- st and ard deviation , 64.9+/-13.5 y ) with a poststroke interval of 26.0+/-8.8 days . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Peak exercise capacity ( VO(2)peak ) was measured by open-circuit spirometry during maximal effort treadmill walking with 15 % body-weight support . RESULTS Mean VO(2)peak was 14.4+/-5.1 mL. kg(-1 ) . min(-1 ) or 60%+/-16 % of age- and sex-related normative values for sedentary healthy adults . CONCLUSIONS Exercise capacity approximately 1 month after stroke was compromised . Further research is needed to eluci date the physiologic basis of this low capacity", "Background – Transient ischemic attack ( TIA ) and stroke patients often show a striking lack of knowledge about their disease . We developed a computer program that provided health education fitting the educational level , risk profile and symptoms of patients and evaluated it in a r and omized controlled trial", "ABSTRACT Stroke survivors are at high risk for cardiovascular mortality which can be in part mitigated by increasing physical activity . Self-efficacy for exercise is known to play a role in adoption of exercise behaviors . This study examines self-reported psychological outcomes in a group of 64 stroke survivors r and omized to either a 6-month treadmill training program or a stretching program . Results indicated that , regardless of group , all study participants experienced increased self-efficacy ( F = 2.95 , p = .09 ) and outcome expectations for exercise ( F = 13.23 , p improvements in activities of daily living as reported on the Stroke Impact Scale ( F = 10.97 , p = .002 ) . No statistically significant between-group differences were noted , possibly because of the fact that specific interventions design ed to enhance efficacy beliefs were not part of the study . Theoretically based interventions should be tested to clarify the role of motivation and potential influence on exercise and physical activity in the stroke survivor population", "BACKGROUND Determinants of survival and of risk of vascular events after transient ischaemic attack ( TIA ) or minor ischaemic stroke are not well defined in the long term . We aim ed to re study these risks in a prospect i ve cohort of patients after TIA or minor ischaemic stroke ( Rankin grade METHODS We assessed the survival status and occurrence of vascular events in 2473 participants of the Dutch TIA Trial ( recruitment in 1986 - 89 ; arterial cause of cerebral ischaemia ) . We included 24 hospitals in the Netherl and s that recruited at least 50 patients . Primary outcomes were all-cause mortality and the composite event of death from all vascular causes , non-fatal stroke , and non-fatal myocardial infa rct ion . We assessed cumulative risks by Kaplan-Meier analysis and prognostic factors with Cox univariate and multivariate analysis . FINDINGS Follow-up was complete in 2447 ( 99 % ) patients . After a mean follow-up of 10.1 years , 1489 ( 60 % ) patients had died and 1336 ( 54 % ) had had at least one vascular event . 10-year risk of death was 42.7 % ( 95 % CI 40.8 - 44.7 ) . Age and sex-adjusted hazard ratios were 3.33 ( 2.97 - 3.73 ) for age over 65 years , 2.10 ( 1.79 - 2.48 ) for diabetes , 1.77 ( 1.45 - 2.15 ) for claudication , 1.94 ( 1.42 - 2.65 ) for previous peripheral vascular surgery , and 1.50 ( 1.31 - 1.71 ) for pathological Q waves on baseline electrocardiogram . 10-year risk of a vascular event was 44.1 % ( 42.0 - 46.1 ) . After falling in the first 3 years , yearly risk of a vascular event increased over time . Predictive factors for risk of vascular events were similar to those for risk of death . INTERPRETATION Long-term secondary prevention in patients with cerebral ischaemia still has room for further improvement", "OBJECTIVE To investigate the effect of early aerobic training on the aerobic and functional abilities of patients in the subacute stage of cerebrovascular accident ( CVA ) . DESIGN R and omized controlled trial . SETTING Rehabilitation unit in Israel . PARTICIPANTS Ninety-two patients who had a first CVA were r and omly assigned to an exercise-training group or to a control group . INTERVENTION Aerobic training with a leg cycle ergometer for 8 weeks . MAIN OUTCOME MEASURES Workload , exercise time , resting and submaximal blood pressure and heart rate , and functional abilities . RESULTS A trend toward improvement was found in all aerobic parameters for the experimental group , but only heart rate at rest ( P=.02 ) , workload , and work time ( P parameters of function for the experimental group , but only stair climbing was significantly better ( P aerobic training on walking distance . Although no significant effect was found in the group of younger patients ( aged , a significant difference in favor of training was noted in the group of older patients . CONCLUSIONS Patients with CVA in the subacute stage improved some of their aerobic and functional abilities after submaximal aerobic training", "OBJECTIVE To investigate gait outcomes with supported treadmill ambulation training ( STAT ) associated with regular rehabilitation in acute stroke survivors . DESIGN R and omized controlled trial , pilot study . SETTING Rehabilitation medicine service at a Veterans Affairs medical center . PARTICIPANTS Seven acute stroke survivors assigned to regular intervention group and 6 patients assigned to STAT intervention . INTERVENTIONS Regular intervention consisted of 3 hours daily of physical therapy , kinesiotherapy , and occupational therapy . STAT group received regular rehabilitation with STAT substituted for usual gait training . Participants were tested at baseline , treated for an average of 3 weeks , and retested on discharge . The analysis of covariance procedure was used to test for differences between the 2 approaches . MAIN OUTCOME MEASURES Functional Ambulation Category Scale , gait speed , walking distance , gait energy expenditure , and gait energy cost . RESULTS The small sample size did not generate enough power to detect significant differences in any variable . However , medium to large effect sizes of 0.7 and 1.16 st and ard deviation units were observed for gait energy cost and walk distance , respectively . CONCLUSIONS This pilot study indicated that STAT is a safe , feasible , and promising intervention for acute stroke survivors . A larger trial is warranted for statistical relevance", "Abstract Goal : Evidence -based guidelines exist for the prevention and treatment of patients with cerebral ischemia . Despite these guidelines , there are gaps in clinical practice . Our study aim ed to determine if a physician-directed , nurse-case-management program could reduce individual patient vascular risk factors . Methods : Patients hospitalized with atherosclerotic cerebral ischemia with ≥ 1 major uncontrolled risk factor for stroke ( hypertension , tobacco use , dyslipidemia , diabetes ) were eligible to enroll in our study . Patients were r and omized to management by the nurse-prevention program or usual care . Patients in the usual-care group received their initial risk-factor assessment and a scheduled follow-up at 1 year . Patients in the usual-care group underwent further follow-up by primary care and /or neurology as recommended during their hospitalization or outpatient visit . Patients assigned to the prevention group received individualized education , motivational interviewing , and were aided in setting up their risk-factor modification goal plan . Additional education was tailored to each patient based on individualized risk factors . Prevention-group patients also underwent consultation with a registered dietitian and an exercise physiologist . The primary endpoint of the study was improvement of ≥ 1 major patient risk factor for occurrence of stroke to goal at 1 year . Results : At 1-year post-hospitalization , patients in the nurse-care-management group were 42 % more likely to have met the primary endpoint ( n = 18 ; 61 % nurse-managed patients ) compared with 33 % ( n = 18 ) of patients undergoing usual care ( P = 0.09 ) . There was no significant reduction in minor risk factors for either patient group . Patients in the prevention group had greater reductions in low-density lipoprotein cholesterol levels ( −38 vs −4 ; P = 0.0083 ) , changes in cardiovascular risk score ( −5.2 vs 1.3 ; P = 0.0033 ) , and had a greater reductions in systolic blood pressure ( −12.2 vs −0.105 ; P = 0.07 ) than their usual-care counterparts ( changes shown respectively ) . Patients in the prevention group were more likely to follow a prescribed diet than those in the usual-care group ( 50 % ) vs 7 % , respectively ; P = 0.0070 ) and maintain an exercise program ( 83 % vs 33 % , respectively ; P = 0.0018 ) . Summary : A physician-directed , nurse case-management system for patients post-hospitalization for cerebral ischemia is feasible and may help improve long-term control of major patient risk factors for stroke . A larger trial is needed to verify trends noted in our study", "SIR— Interventions with an educational or counselling component have been reported to be effective in a variety of patient groups to encourage smoking cessation [ 1 ] , lower blood pressure ( BP ) [ 2 , 3 ] , achieve modest reductions in cholesterol [ 4 ] , and promote weight loss [ 5 ] . Evaluation of the impact of education on physical outcomes is lacking in stroke disease , despite evidence that inadequate provision of information may adversely affect compliance with secondary prevention and psychosocial outcomes [ 6 ] . We describe a single-blind r and omised controlled trial of health education and counselling for patients with stroke or transient ischaemic attack ( TIA ) , and its effects on risk factors , satisfaction , mood and perceived health status", "BACKGROUND AND PURPOSE In hemiparetic individuals , low endurance to exercise may compound the increased energy cost of movement and contribute to poor rehabilitation outcomes . The purpose of this investigation was to describe how hemiparetic stroke patients responded to intense exercise and aerobic training . METHODS Forty-two subjects were r and omly assigned to an exercise training group or to a control group . Treatments were given three times per week for 10 weeks in similar laboratory setting s. Baseline and posttest measurements were made of maximal oxygen consumption , heart rate , workload , exercise time , resting and submaximal blood pressures , and sensorimotor function . RESULTS Only experimental subjects showed significant improvement in maximal oxygen consumption , workload , and exercise time . Improvement in sensorimotor function was significantly related to the improvement in aerobic capacity . After treatment , experimental subjects showed significantly lower systolic blood pressure at submaximal workloads during the grade d exercise test . CONCLUSIONS We conclude that hemiparetic stroke patients may improve their aerobic capacity and submaximal exercise systolic blood pressure response with training . Sensorimotor improvement is related to the improvement in aerobic capacity", "Background and objective . In spite of the challenges , engaging in exercise programs very early after stroke may positively influence aerobic capacity and stroke-related outcomes , including walking ability . The objective of this study was to evaluate the feasibility of adding aerobic cycle ergometer training to conventional rehabilitation early after stroke and to determine effects on aerobic capacity , walking ability , and health-related quality of life . Methods . A prospect i ve matched control design was used . All participants performed a grade d maximal exercise test on a semi-recumbent cycle ergometer , spatiotemporal gait assessment s , 6-Minute Walk Test , and Stroke Impact Scale . The Exercise group added 30 minutes of aerobic cycle ergometry to conventional inpatient rehabilitation 3 days/week until discharge ; the Control group received conventional rehabilitation only . Results . All Exercise participants ( n = 23 ) completed the training without adverse effects . In the 18 matched pairs , both groups demonstrated improvements over time with a trend toward greater aerobic benefit in the Exercise group with 13 % and 23 % increases in peak VO2 and work rate respectively , compared to 8 % and 16 % in the Control group ( group-time interaction P = .71 and .62 ) . A similar trend toward improved 6-Minute Walk Test distance ( Exercise 53 % vs Controls 23 % , P = .23 ) was observed . Conclusion . Early aerobic training can be safely implemented without deleterious effects on stroke rehabilitation . A trend toward greater improvement in aerobic capacity and walking capacity suggests that such training may have an early beneficial effect and should be considered for inclusion in rehabilitation programs" ]	411888b2-06ff-11f0-808a-c43d1ab1c353
OBJECTIVES EQ-5D is widely used in studies with adults as a source of generic health-related quality of life information and utility weights to inform re source allocation decisions . This method ological systematic review describes the extent to which EQ-5D has been used in the evaluation of children 's health care , assesses psychometric properties , and makes recommendations for future good practice . METHODS Systematic search es of data bases and the Internet to identify studies published during 2000 - 2010 that either used EQ-5D with children younger than age 19 years as an outcome measure or reported psychometric data . Study characteristics , including measures and psychometric data , were extracted into tables for analysis . RESULTS We identified 29 studies that used four versions of the EQ-5D : adult EQ-5D , EQ-5D-Y , Dutch EQ-5D child , and extended with cognitive dimension , EQ-5D+C. Twelve of 29 studies did not specify the EQ-5D version used . Existing literature lacks detail on the specific use of EQ-5D and its potential effects on findings . Version use and psychometric properties were inadequately reported . There are large gaps in current knowledge of psychometric properties across all versions when used with children . CONCLUSIONS For reasons of comparability with re source use across adult and children 's services , there are arguments for continued use of EQ-5D in studies with children . We recommend use of EQ-5D alongside children-specific quality of life measures and disease-specific measures . Research ers are encouraged to undertake method ological and philosophical analyses to better underst and and improve evidence as to how adults who make decisions about re source allocation can best take account of children in decision making	[ "Background Asthma is a chronic lung disease in which recurrent asthma symptoms create a substantial burden to individuals and their families . At the same time the economic burden associated with asthma is considerable . Methods The cost-effectiveness study was part of a single centre prospect i ve r and omised controlled trial comparing a nurse-led telemonitoring programme to usual care in a population of asthmatic out patients . The study included 109 asthmatic out patients ( 56 children ; 53 adults ) . The duration of follow-up was 12 months , and measurements were performed at baseline , 4 , 8 , and 12 months . Patients were asked to transfer their monitor data at least twice daily and by judging the received data and following a stepwise intervention protocol a nurse was able to act as the main caregiver in the intervention group . In both groups the EQ-5D and the SF-6D were used to obtain estimates of health state utilities . One year health care costs , patient and family costs , and productivity losses were calculated . The mean incremental costs were weighted against the mean incremental effect in terms of QALY . Results The study population generally represented mild to moderate asthmatics . No significant differences were found between the groups with regard to the generic quality of life . Overall , the mean health care costs per patient were higher in the intervention group than in the control group . The intervention costs mainly caused the cost difference between the groups . The intervention costs the society € 31,035/QALY gained with regard to adults and with regard to children € 59,071/QALY gained . Conclusion If the outcome is measured by generic quality of life the nurse-led telemonitoring programme is of limited cost-effectiveness in the study population . From the societal perspective the probability of the programme being cost-effective compared to regular care was 85 % at a ceiling ratio of € 80,000/QALY gained among the adults and 68 % among the children . A decrease in the price of the asthma monitor will substantial increase the probability of the programme to be cost-effective . Trial registration Number :", "The high cost of treating patients with inhibitors in an environment of restricted budgets warrants consideration of cost-effectiveness . We determined the clinical response , effect on quality of life and the cost-effectiveness of treatment with rFVIIa in six boys with long-st and ing inhibitors to factors VIII or IX , compared with other treatment regimes previously used in these patients . The study used a longitudinal before- and -after design and was conducted in three phases . Phase 1 was 6 months preceding the introduction of rFVIIa , during which patients received on-dem and ' usual care ' with other treatment regimes ; phase 2 was 6 months treatment on rFVIIa assessed retrospectively ; and phase 3 was 6 months on rfVIIa treatment assessed prospect ively . Treatment with rFVIIa was reserved for intrarticular , compartment , psoas , mucosal and suspected intracranial bleeding . Treatment outcomes were obtained by interview using structured question naires , the quality -of-life instruments CHQ CF-80 and CHQ PF-50 , patient self-reporting diary , interrogation of hospital records , and the EuroQoL EQ-5D for utility valuations . Our results confirm that rFVIIa is clinical ly effective and result ed in 63 - 92 % reductions in the number of re-treatments , duration of painful episodes , delay to initiation of treatment , days requiring wheelchair or crutches , emergency room visits and lost carer time compared with the patients ' other therapies . Quality -of-life improvements were observed in several important areas as perceived by both patients and their families , at an incremental cost per QALY of A$ 51 533", "We evaluated 4 different health‐related quality of life ( HRQL ) measures prospect ively to determine their ability to detect change over time : the Health Utilities Index Mark 2 and Mark 3 , the Pediatric Quality of Life Inventory ( PedsQL ) 4.0 Generic Core and Cancer Module , the EuroQol EQ‐5D visual analogue scale ( EuroQol ) , and the Lansky Play‐Performance Scale", "Abstract Objectives : To explore whether Alzheimer ’s disease patients could rate their quality of life ( QOL ) using utility-based health indexes , and to provide new knowledge about the measurement properties of these instruments for patient and caregiver proxy ratings . Methods : A convenience sample of 60 mild-moderate AD patients and their caregivers were r and omized to complete the Quality of Well-Being Scale ( QWB ) , Health Utilities Index ( HUI3 ) or EQ-5D and visual analogue scale ( VAS ) on two occasions . Test – retest reliability ( intraclass correlation coefficients ) and convergent validity ( Spearman correlations ) of utility scores with global health status , activities of daily living , comorbidity , mood , cognition and other utility measures were assessed . Results : Completion time was shortest for the combined EQ-5D and VAS . For patients with mild dementia and for proxies , reliability was ≥ 0.70 for the EQ-5D , QWB and HUI3 . The EQ-5D had a ceiling effect for patient ratings . Convergent validity was demonstrated for patient and proxy ratings , with the strongest validity for EQ-5D ratings and the weakest validity for HUI3 patient ratings . Mean patient utility scores were significantly higher than mean proxy scores for all measures ( p<0.001 ) . Conclusions : For patient and proxy ratings , the EQ-5D had the best combination of measurement properties , although it had a substantial ceiling effect for patient ratings . Proxy QOL ratings did not accurately reflect patients ’ ratings", "We prospect ively compared the proxy reporting of health‐related quality of life ( HRQL ) by parents and nurses of children with Hodgkin disease to see how well they correlated with the children 's report", "The Health Utilities Index Mark 2 ( HUI:2 ) is a generic multiattribute , preference-based system for assessing health-related quality of life . Health Utilities Index Mark 2 consists of two components : a seven-attribute health status classification system and a scoring formula . The seven attributes are sensation , mobility , emotion , cognition , self-care , pain , and fertility . A r and om sample of general population parents were interviewed to determine cardinal preferences for the health states in the system . The health states were defined as lasting for a 60-year lifetime , starting at age 10 . Values were measured using visual analogue scaling . Utilities were measured using a st and ard gamble technique . A scoring formula is provided , based on a multiplicative multiattribute utility function from the responses of 194 subjects . The utility scores are death-anchored ( death = 0.0 ) and form an interval scale . Health Utilities Index Mark 2 and its utility scores can be useful to other research ers in a wide variety of setting s who wish to document health status and assign preference scores", "OBJECTIVE Changes in health-related quality of life ( HRQOL ) and self-esteem were studied in children with idiopathic short stature ( ISS ) participating in a study on the effect of growth hormone treatment . STUDY DESIGN Prepubertal children ( n = 36 ) with ISS were r and omly assigned to a treatment or control group . Children with ISS , their parents , and the pediatrician completed HRQOL and self-esteem question naires 3 times in 2 years . RESULTS At the start , children with ISS did not have lower scores than the norm population , except for social functioning HRQOL . The pediatrician reported an improvement of HRQOL in the treatment group , the parents reported no change , and the children in the treatment group reported the same , or sometimes even worse , HRQOL or self-esteem than the control group . Changes related to the child 's satisfaction with height and hardly to growth itself . CONCLUSION The assumption that growth hormone treatment improves HRQOL in children with ISS could not be supported in this study", "This paper reports on the findings from applying a new approach to modelling health state valuation data . The approach applies a nonparametric model to estimate SF-6D health state utility values using Bayesian methods . The data set is the UK SF-6D valuation study where a sample of 249 states defined by the SF-6D ( a derivative of the SF-36 ) was valued by a representative sample of the UK general population using st and ard gamble . The paper presents the results from applying the nonparametric model and comparing it to the original model estimated using a conventional parametric r and om effects model . The two models are compared theoretically and in terms of empirical performance . The paper discusses the implication s of these results for future applications of the SF-6D and further work in this field", "OBJECTIVES To compare the effects of combined hydrotherapy and l and -based physiotherapy ( combined ) with l and -based physiotherapy only ( l and ) on cost , health-related quality of life ( HRQoL ) and outcome of disease in children with juvenile idiopathic arthritis ( JIA ) . Also to determine the cost-effectiveness of combined hydrotherapy and l and -based physiotherapy in JIA . DESIGN A multicentre r and omised controlled , partially blinded trial was design ed with 100 patients in a control arm receiving l and -based physiotherapy only ( l and group ) and 100 patients in an intervention arm receiving a combination of hydrotherapy and l and -based physiotherapy ( combined group ) . SETTING Three tertiary centres in the UK . PARTICIPANTS Patients aged 4 - 19 years diagnosed more than 3 months with idiopathic arthritides , onset before their 16th birthday , stable on medication with at least one active joint . INTERVENTIONS Patients in the combined and l and groups received 16 1-hour treatment sessions over 2 weeks followed by local physiotherapy attendances for 2 months . MAIN OUTCOME MEASURES Disease improvement defined as a decrease of > or = 30 % in any three of six core set variables without there being a 30 % increase in more than one of the remaining three variables was used as the primary outcome measure and assessed at 2 months following completion of intervention . Health services re source use ( in- and outpatient care , GP visits , drugs , interventions , and investigations ) and productivity costs ( parents ' time away from paid work ) were collected at 6 months follow-up . HRQoL was measured at baseline and 2 and 6 months following intervention using the EQ-5D , and quality -adjusted life-years ( QALYs ) were calculated . Secondary outcome measures at 2 and 6 months included cardiovascular fitness , pain , isometric muscle strength and patient satisfaction . RESULTS Seventy-eight patients were recruited into the trial and received treatment . Two months after intervention 47 % patients in the combined group and 61 % patients in the l and group had improved disease with 11 and 5 % with worsened disease , respectively . The analysis showed no significant differences in mean costs and QALYs between the two groups . The combined group had slightly lower mean costs ( -6.91 pounds Sterling ) and lower mean QALYs ( -0.0478 , 95 % confidence interval -0.11294 to 0.0163 based on 1000 bootstrap replications ) . All secondary measures demonstrated a mean improvement in both groups , with the combined group showing greater improvements in physical aspects of HRQoL and cardiovascular fitness . CONCLUSIONS JIA is a disease in which a cure is not available . This research demonstrates a beneficial effect from both combined hydrotherapy and l and -based physiotherapy treatment and l and -based physiotherapy treatment alone in JIA without any exacerbation of disease , indicating that treatments are safe . The caveat to the results of the cost-effectiveness and clinical efficacy analysis is that the restricted sample size could have prevented a true difference being detected between the groups . Nevertheless , there appears to be no evidence to justify the costs of building pools or initiating new services specifically for use in this disease . However , this conclusion may not apply to patients with unremitting active disease who could not be entered into the trial because of specified exclusion criteria . For this group , hydrotherapy or combined treatment may still be the only physiotherapy option . Further research is suggested into : the investigation and development of appropriate and sensitive outcome measures for use in future hydrotherapy and physiotherapy trials of JIA ; preliminary studies of method ologies in complex interventions such as physiotherapy and hydrotherapy to improve recruitment and ensure protocol is acceptable to patients and carers ; hydrotherapy in the most common paediatric user group , children with neurological dysfunction , ensuring appropriate outcome measures are available and method ologies previously tried ; patient satisfaction and compliance in l and -based physiotherapy and hydrotherapy and European studies of hydrotherapy in rare disorders such as JIA" ]	411888ee-06ff-11f0-808a-c43d1ab1c353
This systematic review summarizes the outcome reporting st and ards in Dupuytren ’s disease treatment research . A search of Ovid Medline , Ovid Embase , and CINAHL was conducted . R and omized controlled trials , cohort studies , and case series published between 1997 and 2017 , investigating treatment of Dupuytren ’s disease with fasciectomy , fasciotomy , or collagenase , were eligible for inclusion . Range of motion was the most commonly reported outcome , appearing in 77 % of included studies . Outcomes , such as range of motion , recurrence , and clinical success , were frequently defined , however many different definitions were used . We identified 37 unique measurement methods for range of motion , 28 for recurrence , and 25 for clinical success . Most outcomes were assessed at multiple time points , and only a few studies reported results according to established clinical significance thresholds . Development of a core outcome set will help st and ardize outcome reporting , and ensure future research in this field is relevant , interpretable , and amenable to systematic review and /or meta- analysis	[ "Objectives To compare collagenase injections and surgery ( fasciectomy ) for Dupuytren 's contracture ( DC ) regarding actual total direct treatment costs and short-term outcomes . Design Retrospective cohort study . Setting Orthopaedic department of a regional hospital in Sweden . Participants Patients aged 65 years or older with previously untreated DC of 30 ° or greater in the metacarpophalangeal ( MCP ) and /or proximal interphalangeal ( PIP ) joints of the small , ring or middle finger . The collagenase group comprised 16 consecutive patients treated during the first 6 months following the introduction of collagenase as treatment for DC at the study centre . The controls were 16 patients r and omly selected among those operated on with fasciectomy at the same centre during the preceding 3 years . Interventions Treatment with collagenase was given during two st and ard outpatient clinic visits ( injection of 0.9 mg , distributed at multiple sites in a palpable cord , and next-day finger extension under local anaesthesia ) followed by night-time splinting . Fasciectomy was carried out in the operating room ( day surgery ) under general or regional anaesthesia using st and ard technique , followed by therapy and splinting . Primary and secondary outcome measures Actual total direct costs ( salaries of all medical personnel involved in care , medications , material s and other relevant costs ) , and total MCP and PIP extension deficit ( degrees ) measured by h and therapists at 6–12 weeks after the treatment . Results Collagenase injection required fewer hospital outpatient visits to a therapist and nurse than fasciectomy . Total treatment cost for collagenase injection was US$ 1418.04 and for fasciectomy US$ 2102.56 . The post-treatment median ( IQR ) total extension deficit was 10 ( 0–30 ) for the collagenase group and 10 ( 0–34 ) for the fasciectomy group . Conclusions Treatment of DC with one collagenase injection costs 33 % less than fasciectomy with equivalent efficacy at 6 weeks regarding reduction in contracture ", "PURPOSE Collagenase Clostridium histolyticum ( CCH ) injection was introduced commercially as a treatment for Dupuytren contracture following initial phase-3 investigations in 2009 with promising results . However , the efficacy of CCH has not been prospect ively investigated in a direct comparison to other active treatments of Dupuytren contracture with more than 1-year follow-up , despite a wide and increasing clinical use . METHOD In this prospect i ve , independent , open-label , r and omized controlled trial , ( Clinical trials.gov ; NCT 01538017 ) , percutaneous needle fasciotomy ( PNF ) was directly compared with CCH . Fifty patients with primary isolated proximal interphalangeal joint Dupuytren contractures were enrolled and followed for 2 years . The primary outcome was clinical improvement defined as a reduction in contracture by 50 % or more relative to baseline . Secondary outcomes included change in contracture , recurrence , adverse events , complications , and Disabilities of the Arm , Shoulder , and H and question naire score . RESULTS Clinical improvement at 2 years was maintained in 7 % of CCH patients ( 2 of 29 ) and 29 % of PNF patients ( 6 of 21 ) . Collagenase Clostridium histolyticum led to more , mainly transient , complications , in 93 % of patients versus 24 % of the patients treated with PNF . No other differences were observed . CONCLUSIONS This study provides evidence that CCH is not superior to PNF in the treatment of isolated proximal interphalangeal joint Dupuytren contracture regarding clinical outcome , and it led to more complications than PNF . TYPE OF STUDY /LEVEL OF EVIDENCE Therapeutic", "Abstract Background Dupuytren ’s disease ( DD ) is a fibroproliferative pathology that affects the palmar aponeurosis causing the development of nodules and collagen cords and the progressive flexion of the fingers . The st and ard procedure is surgical fasciectomy , followed by high recurrence rates . Collagenase Clostridium histolyticum ( CCH ) injection represents an innovative noninvasive approach to the treatment of DD . This prospect i ve study was design ed to examine the efficacy and safety of CCH injection performed in the outpatient , using local anesthesia . Material s and methods Forty patients [ 32 metacarpophalangeal ( MP ) , 8 proximal interphalangeal ( PIP ) ] with Dupuytren ’s contracture of at least 20 ° for MP joint and any degree for PIP joint were included . The mean age was 66 . All joints were treated with a single vial of collagenase injection and manual breaking of the cord 24 h after . All adverse effects ( AEs ) were monitored . Patients were checked 7 , 30 , 90 , and 180 days after the injection . Primary endpoint was a reduction in digit contracture within 0 ° –5 ° of normal extension . Secondary endpoints were the improvement of range of motion , the evaluation of AEs incidence , and cost-effectiveness of collagenase treatment . Results About 67.5 % of patients obtained a clinical success . At 6 months , a further 7.5 % attained the same result . The mean contracture of treated joints was 5.3º for MP and 6.8 ° for PIP joints . Twenty-three patients had one or more mild-to-moderate side effects . Conclusions The use of collagenase appears to be an effective and safe method for the treatment of Dupuytren ’s contracture . Therapeutic success was achieved in a significant percentage of patients . The incidence of side effects was higher , but they were local reactions of short duration . The use of a single collagenase vial in patients treated in day surgery appears more cost-effective than surgery", "PURPOSE This study compared the efficacy of collagenase treatment and needle fasciotomy for contracture of the metacarpophalangeal ( MCP ) joint in Dupuytren disease . METHODS This is a prospect i ve , single-blinded , r and omized study with follow-up 1 week and 1 year after treatment . One hundred and forty patients with an MCP contracture of 20 ° or more in a single finger were enrolled , of whom 69 patients were r and omized to collagenase treatment and 71 patients to needle fasciotomy . The patients were followed at 1 week and were examined by a physiotherapist after 1 year . Measurements of joint movement and grip strength were recorded as well as patient-perceived outcomes measured by the Unité Rhumatologique des Affections de la Main ( URAM ) question naire and a visual analog scale ( VAS ) for the estimation of procedural pain and subjective treatment efficacy . RESULTS Eighty-eight percent of the patients in the collagenase group and 90 % of the patients in the needle fasciotomy group had a reduction in their MCP contracture to less than 5 ° 1 week after treatment , and the median gains in passive MCP movement were 48 ° and 46 ° , respectively . The median VAS score for procedural pain was 4.9 of 10 in the collagenase group and 2.7 of 10 in the needle fasciotomy group . After 1 year , 90 % of the patients in both groups had full extension of the treated MCP joint . One patient in each group had a recurrence of the contracture . The median improvement in URAM score was 8 units in both groups and the VAS estimation of treatment efficacy by the patients was 8.7 of 10 in both groups . CONCLUSIONS There was no significant difference between the treatment outcomes after collagenase and needle fasciotomy treatment after 1 year . TYPE OF STUDY /LEVEL OF EVIDENCE Therapeutic", "In POINT X , a study design ed to reflect clinical practice and patient treatment choices , 254 European patients received open-label collagenase for Dupuytren ’s contracture . The most severely affected joint was treated first in 74 % of patients . In total , 52 % , 41 % , 7 % , and 1 % of patients selected the little , ring , middle , and index finger , respectively ; 79 % had one or two joints treated . Only 9 % of patients ( n = 24 ) received 4 or 5 injections . The mean improvement in total passive extension deficit ( TPED ) was 34 ° on day 1 , improving further by day 7 to 42 ° . This secondary improvement was maintained by day 90 and month 6 . The mean number of injections/joint was 1.2 for the metacarpophalangeal joint and 1.25 for the proximal interphalangeal joint . Median time to recovery was 4 days ; the mean improvement in h and function was clinical ly relevant as measured by the Unité Rhumatologique des Affections de la Main ( URAM ) score . In total , 87 % and 86 % of patients and physicians , respectively , were very satisfied or satisfied with treatment at month 6 , although correlation between TPED and patient satisfaction was weak ( Spearman −0.18 , 95 % CI −0.32 to −0.06 ) . Collagenase was well tolerated , with 10 ( 3.9 % ) patients experiencing severe adverse events . As a real-world study , the POINT X findings can be generalized to the at-large population", "PURPOSE The Collagenase Option for the Reduction of Dupuytren 's ( CORD ) II study investigated the efficacy and safety of injectable Xiaflex ( collagenase clostridium histolyticum ) , in patients with Dupuytren 's contracture . METHODS This was a prospect i ve , r and omized , placebo-controlled trial with 90-day double-blind and 9-month open-label phases . We r and omized patients with contractures affecting metacarpophalangeal ( MCP ) or proximal interphalangeal ( PIP ) joints 2 to 1 to collagenase ( 0.58 mg ) or placebo . Cords received a maximum of 3 injections . Cord disruption was attempted the day after injection using a st and ardized finger extension procedure . Primary end point was reduction in contracture to 0 ° to 5 ° of normal 30 days after the last injection . RESULTS We enrolled 66 patients ; 45 cords ( 20 MCP to 25 PIP joints ) received collagenase and 21 cords ( 11 MCP to 10 PIP joints ) received placebo in the double-blind phase . Statistically significantly more cords injected with collagenase than placebo met the primary end point ( 44.4 % vs 4.8 % ; p ) . The mean percentage decrease in degree of joint contracture from baseline to 30 days after last injection was 70.5 % ± 29.2 % in the collagenase group and 13.6 % ± 26.1 % in the placebo group ( p ) . The mean increase in range of motion was significantly greater in the collagenase ( 35.4 ° ± 17.8 ° ) than in the placebo ( 7.6 ° ± 14.9 ° ; p group . Efficacy after open-label treatment was similar to that after the double-blind phase : 50.7 % of all joints achieved 0 ° to 5 ° of normal . More patients were satisfied with collagenase ( p No joint had recurrence of contracture . One patient had a flexion pulley rupture and one patient underwent routine fasciectomy to address cord proliferation and sensory abnormality . No tendon ruptures or systemic allergic reactions were reported . Most adverse events were related to the injection or finger extension procedure . CONCLUSIONS Collagenase clostridium histolyticum is the first Food and Drug Administration-approved , nonsurgical treatment option for adult Dupuytren 's contracture patients with a palpable cord that is highly effective and well tolerated . TYPE OF STUDY /LEVEL OF EVIDENCE Therapeutic", "PURPOSE To describe changes in joint motion , sensibility , and scar pliability and to investigate the patients ' expectations , self-reported recovery , and satisfaction with h and function , disability , and quality of life after surgery and h and therapy for Dupuytren disease . METHODS This prospect i ve cohort study collected measurements before surgery and 3 , 6 , and 12 months after surgery and h and therapy . Ninety patients with total active extension deficits of 60 ° or more from Dupuytren contracture were included . Outcomes measures were range of motion ; sensibility ; scar pliability ; self-reported outcomes on expectations , recovery , and satisfaction with h and function ; Disabilities of the Arm , Shoulder , and H and scores ; safety and social issues of h and function ; physical activity habits ; and quality of life with the Euroqol . RESULTS The extension deficit decreased , and there was a transient decrease in active finger flexion during the first year after surgery . Sensibility remained unaffected . Generally , patients with surgery on multiple fingers had worse scar pliability . The majority of the patients had their expectations met , and at 6 months , 32 % considered h and function as fully recovered , and 73 % were satisfied with their h and function . Fear of hurting the h and and worry about not trusting the h and function were of greatest concern among safety and social issues . The Disability of the Arm , Shoulder , and H and score and the Euroqol improved over time . CONCLUSIONS After surgery and h and therapy , disability decreased independent of single or multiple operated fingers . The total active finger extension improved enough for the patients to reach a functional range of motion despite an impairment of active finger flexion still present 12 months after treatment . TYPE OF STUDY /LEVEL OF EVIDENCE Therapeutic IV", "AIM We explored regional variations in the surgical management of patients with Dupuytren 's contracture ( DC ) in 12 European countries using a surgeon survey and patient chart review . METHODS Twelve countries participated : Denmark , Finl and , Sweden ( Nordic region ) ; Czech Republic , Hungary , Pol and ( East ) ; France , Germany , the Netherl and s , UK ( West ) ; Italy , Spain ( Mediterranean ) . For the survey , a r and om sample of orthopaedic/plastic surgeons ( n = 687 ) with 3 - 30 years ' experience was asked about DC procedures performed during the previous 12 months . For the chart review ( n = 3357 ) , information from up to five consecutive patients was extracted . Descriptive statistics are reported . RESULTS Ninety-five per cent of all surgeons used fasciectomy for DC , followed by fasciotomy ( 70 % ) , dermofasciectomy ( 38 % ) and percutaneous needle fasciotomy ( 35 % ) . Most surgeons were satisfied with fasciectomy over other procedures . Recommended time away from work and duration of physical therapy increased with the invasiveness of the procedure . The intra-operative complication rate was 4.0 % ; the postoperative complication rate was 34 % . Overall , ≥ 97 % of the procedures were rated by surgeons as having a positive outcome . Across all regions , 54 % of patients had no nodules or contracture after the procedures . Only 2 % of patients required retreatment within the first year of surgery . Important inter- and intraregional differences in these aspects of patient management are described . CONCLUSIONS Underst and ing current regional treatment patterns and their relationships to country-specific health systems may facilitate earlier identification of , and intervention for , DD and help to optimise the overall treatment for patients with this chronic condition", "STUDY DESIGN Prospect i ve cohort study . INTRODUCTION The evidence of the relationship between functional recovery and impairment after surgery and h and therapy are inconsistent . PURPOSE OF THE STUDY To explore factors that were most related to functional recovery as measured by DASH in patients with Dupuytren 's disease . METHODS Eighty-one patients undergoing surgery and h and therapy were consecutively recruited . Functional recovery was measured by the Disability of the Arm , Shoulder and H and ( DASH ) question naire . Explanatory variables : range of motion of the finger joints , five questions regarding safety and social issues of h and function , and health-related quality of life ( Euroqol ) . RESULTS The three variables \" need to take special pre caution s \" , \" avoid using the h and in social context \" , and health-related quality of life ( EQ-5D index ) explained 62.1 % of the variance in DASH , where the first variable had the greatest relative effect . DISCUSSION Safety and social issues of h and function and quality of life had an evident association with functional recovery . LEVEL OF EVIDENCE IV", "Background The conventional treatment for Dupuytren ’s disease is surgery . The introduction of alternative treatment strategies creates a need to track outcomes and costs relating to surgical treatment and risk factors , such as smoking and diabetes . This was the aim of the present study . Methods In a prospect i ve study , the outcome of open surgical treatment for finger flexion contracture in Dupuytren ’s disease ( 175 patients ; 182 surgical procedures ) was studied by evaluating valid QuickDASH forms answered by subjects before surgery and one year postoperatively . Data were also obtained from medical records , and preoperative declarations concerning health . Results In all subjects ( median [ 25 % - 75 % percentiles ] age 68 [ 62 - 73 ] ) , the QuickDASH score improved from 22 [ 9 - 36 ] to 5 [ 0 - 18 ] . Smokers ( 27/179 procedures ) were younger and had a more severe degree of disease and dysfunction preoperatively than non-smokers , but the outcome of surgery did not differ between the groups . Subjects with diabetes ( 20/181 procedures ) were younger than those without diabetes , but their disease severity or outcome did not differ . H and specialists operated faster than residents , but the surgical outcome did not differ . Healthcare costs for surgery for Dupuytren ’s contracture were $ 2392 ( € 1859 ) , which were not higher among smokers or subjects with diabetes . Only 22 patients remained in hospital ( 2 [ 1 - 2.3 ] days ) and 28 patients needed sick leave ( 28 [ 21 - 31 ] days ) . The occurrence of necrosis of skin flaps ( 12 % ) or infections ( 6 % ) was no more frequent among smokers or those with diabetes . Conclusions There is no difference in surgical outcome for finger flexion contracture in Dupuytren ’s disease between smokers and non-smokers or between subjects with or without diabetes , although smokers had more severe preoperative contracture . The costs for surgical treatment for finger flexion contracture in Dupuytren ’s disease should be viewed in relation to that for other treatment strategies", "Background Collagenase clostridium histolyticum ( CCH ) injection for Dupuytren contracture was approved in the USA in 2010 . Current FDA guidelines stipulate that finger manipulation occurs the day following injection . To investigate the safety and efficacy of delaying manipulation to 2 or 4 days following CCH injection , we conducted a prospect i ve , r and omized trial at two sites . Methods Patients with Dupuytren contracture involving the metacarpophalangeal ( MCP ) joint ≥20 ° caused by a palpable cord participated . All patients received one dose of CCH ( 0.58 mg/0.25 ml ) and were followed for 90 days . The primary end point was the percent of patients maintaining clinical success ( reduction of contracture to 0 ° –5 ° ) at 90 days post-injection . Adverse events and change in Michigan H and Question naire ( MHQ ) score were recorded as secondary end points . Results Thirty-seven patients enrolled ; 13 were manipulated on day 1 , 11 on day 2 , and 13 on day 4 . At 30 days after injection , the percentage of patients obtaining reduction of contracture to –5 ° extension was 92 , 82 , and 85 % in groups 1 , 2 , and 3 , respectively , with no significant difference . At 90 days follow-up , the percentage of patients maintaining 0 ° –5 ° extension was 91 , 82 , and 83 % in groups 1 , 2 , and 3 , respectively , with no significant difference . Adverse events were comparable to rates in prior studies . There were no serious adverse events . There was no statistical difference in MHQ scores between groups at any time point . Conclusions Delaying manipulation to day 2 or 4 following CCH injection for MCP joint contractures does not increase adverse events or result in loss of efficacy . Level of Evidence : Therapeutic , Level II", "BACKGROUND AND AIM The options for treating patients with Dupuytren 's contracture have broadened with the introduction of collagenase . Although the literature would suggest that collagenase treatment is effective , has few complications and is popular with patients , it has not been widely commissioned by the National Health Services of the United Kingdom and other European countries due to concerns about cost . The aim of this study was to compare the cost of surgical fasciectomy to collagenase injections for the treatment of Dupuytren 's contracture in a single centre . METHOD Prospect i ve data on 40 patients undergoing fasciectomy or collagenase injection ( 20 patients in each group ) were collected between January and March 2013 . Financial data on the costs of the procedures , equipment , theatre time and follow-up appointments were calculated . RESULTS The average cost of an open partial fasciectomy pathway was £ 7115.34 and that of a collagenase pathway was £ 2110.62 . Eight collagenase patients had physician-led follow-up appointments and only three had h and physiotherapy appointments . By contrast , every fasciectomy patient had at least one physician and one physiotherapist follow-up appointment routinely . CONCLUSION The results of this study demonstrate that collagenase treatment for Dupuytren 's contracture of a single digit in selected patients is just over £ 5000 less than treatment for the same condition using surgical fasciectomy . Collagenase-treated patients require much less physician- and physiotherapist-led postoperative follow-up ", "Background : Controversy exists about the relative effectiveness of injectable collagenase ( collagenase clostridium histolyticum ) and limited fasciectomy in the treatment of Dupuytren ’s contracture . The authors compared the effectiveness of both techniques in actual clinical practice . Methods : This study evaluated all subjects treated with collagenase clostridium histolyticum or limited fasciectomy for metacarpophalangeal and /or proximal interphalangeal joint contractures between 2011 and 2014 at seven practice sites . The authors compared the degree of residual contracture ( active extension deficit ) , Michigan H and Outcomes Question naire scores , and adverse events at follow-up visits occurring between 6 and 12 weeks after surgery or the last injection with the use of propensity score matching . Results : In 132 matched subjects who were treated with collagenase ( n = 66 ) or fasciectomy ( n = 66 ) , the degree of residual contracture at follow-up for affected metacarpophalangeal joints was not significantly different ( 13 degrees versus 6 degrees ; p = 0.095 ) and affected proximal interphalangeal joints had significantly worse residual contracture in the collagenase group compared with those in the fasciectomy group ( 25 degrees versus 15 degrees ; p = 0.010 ) . Collagenase subjects experienced fewer serious adverse events than did fasciectomy subjects and reported larger improvements in the Michigan H and Outcomes Question naire subscores evaluating satisfaction with h and function , activities of daily living , and work performance . Conclusions : This propensity score – matched study showed that collagenase clostridium histolyticum was not significantly different from limited fasciectomy in reducing metacarpophalangeal joint contractures , whereas proximal interphalangeal joint contractures showed slightly better reduction following limited fasciectomy . Collagenase provided a more rapid recovery of h and function than did fasciectomy and was associated with fewer serious adverse events . CLINICAL QUESTION /LEVEL OF EVIDENCE : Therapeutic , III", "BACKGROUND Dupuytren 's disease limits h and function , diminishes the quality of life , and may ultimately disable the h and . Surgery followed by h and therapy is st and ard treatment , but it is associated with serious potential complications . Injection of collagenase clostridium histolyticum , an office-based , nonsurgical option , may reduce joint contractures caused by Dupuytren 's disease . METHODS We enrolled 308 patients with joint contractures of 20 degrees or more in this prospect i ve , r and omized , double-blind , placebo-controlled , multicenter trial . The primary metacarpophalangeal or proximal interphalangeal joints of these patients were r and omly assigned to receive up to three injections of collagenase clostridium histolyticum ( at a dose of 0.58 mg per injection ) or placebo in the contracted collagen cord at 30-day intervals . One day after injection , the joints were manipulated . The primary end point was a reduction in contracture to 0 to 5 degrees of full extension 30 days after the last injection . Twenty-six secondary end points were evaluated , and data on adverse events were collected . RESULTS Collagenase treatment significantly improved outcomes . More cords that were injected with collagenase than cords injected with placebo met the primary end point ( 64.0 % vs. 6.8 % , P range of motion in the joints was significantly improved after injection with collagenase as compared with placebo ( from 43.9 to 80.7 degrees vs. from 45.3 to 49.5 degrees , P localized swelling , pain , bruising , pruritus , and transient regional lymph-node enlargement and tenderness . Three treatment-related serious adverse events were reported : two tendon ruptures and one case of complex regional pain syndrome . No significant changes in flexion or grip strength , no systemic allergic reactions , and no nerve injuries were observed . CONCLUSIONS Collagenase clostridium histolyticum significantly reduced contractures and improved the range of motion in joints affected by advanced Dupuytren 's disease . ( Clinical Trials.gov number , NCT00528606 .", "OBJECTIVES To provide an evidence -based overview of the effectiveness of conservative and (post)surgical interventions for trigger finger , Dupuytren disease , and De Quervain disease . DATA SOURCES Cochrane Library , Physiotherapy Evidence Data base , PubMed , Embase , and CINAHL were search ed to identify relevant systematic review s and r and omized controlled trials ( RCTs ) . DATA SELECTION Two review ers independently applied the inclusion criteria to select potential studies . DATA EXTRACTION Two review ers independently extracted the data and assessed the method ologic quality . DATA SYNTHESIS A best- evidence synthesis was performed to summarize the results . Two review s ( trigger finger and De Quervain disease ) and 37 r and omized controlled trials ( RCTs ) ( trigger finger : n=8 ; Dupuytren disease : n=14 , and De Quervain disease : n=15 ) were included . The trials reported on oral medication ( Dupuytren disease ) , physiotherapy ( De Quervain disease ) , injections and surgical treatment ( trigger finger , Dupuytren disease , and De Quervain disease ) , and other conservative ( De Qervain disease ) and postsurgical treatment ( Dupuytren disease ) . Moderate evidence was found for the effect of corticosteroid injection on the very short term for trigger finger , De Quervain disease , and for injections with collagenase ( 30d ) when looking at all joints , and no evidence was found when looking at the PIP joint for Dupuytren disease . A thumb splint as additive to a corticosteroid injection seems to be effective ( moderate evidence ) for De Quervain disease ( short term and midterm ) . For Dupuytren disease , use of a corticosteroid injection within a percutaneous needle aponeurotomy in the midterm and tamoxifen versus a placebo before or after a fasciectomy seems to promising ( moderate evidence ) . We also found moderate evidence for splinting after Dupuytren surgery in the short term . CONCLUSIONS In recent years , more and more RCTs have been conducted to study treatment of the aforementioned h and disorders . However , more high- quality RCTs are still needed to further stimulate evidence -based practice for patients with trigger finger , Dupuytren disease , and De Quervain disease", "BACKGROUND Our main goal was to see if treatment with collagenase injection is safe and effective and to assess patient satisfaction with this new treatment . METHODS We prospect ively followed 77 consecutive patients , treated for contracture in 91 fingers and 142 joints that received total of 109 collagenase injections . The patients were review ed on the first and second day and at 4 and 12 months . A contracture reduced to five degrees or less at 12 months after the last injection , was considered to be a successful outcome . RESULTS A mean of 1.2 injections were used per patient and 0.8 injections per joint . There was a significant improvement in mean passive extension deficit . Out of the 142 joints treated , 84 ( 59 % ) met our criterion for a successful outcome ; 56 ( 80 % ) out of 70 MCP joints and 28 ( 39 % ) out of 72 PIP joints . There were also significant improvements in both h and function and pain . No serious adverse events were observed . The mean patient satisfaction with the treatment at the 12-month follow up was a VAS score of 78 ( 0 = none ; 100 = complete ) and only 11 % stated that they would not have consented to the treatment if they had known the outcome in advance . CONCLUSIONS Treatment of Dupuytren 's disease with collagenase injection is both safe and effective . It is now our primary treatment for Dupuytren 's disease", "Collagenase clostridium histolyticum is now established as an effective and safe option to treat patients with a single joint affected with Dupuytren ’s contracture . We have extended its use to natatory and combined cords . In a prospect i ve consecutive series of 298 cords in 237 patients , the mean total extension loss improved in cords crossing the metacarpophalangeal joint from 46 ° to 1 ° , in cords crossing the proximal interphalangeal joint from 56 ° to 7 ° , in natatory cords from 130 ° to 25 ° and in combined cords from 102 ° to 16 ° . The immediate correction of combined cords and natatory cords was less reliable than that obtained in cords crossing the metacarpophalangeal joint or proximal interphalangeal joint . Less severe pre-intervention contractures tended to correct better . We found a high complication rate , which may cause alarm . A total of 21 % developed skin splits , with the risk of skin splits generally increasing with more severe pre-injection deformity . Blood blisters were only encountered after manipulation of the more severe contractures . A total of 23 patients ( 8 % ) had a spontaneous rupture and 57 patients ( 19 % ) had a partial spontaneous rupture . Only 4.9 % needed a second injection . We noticed a learning curve , with seven of the first 20 cords ( 35 % ) needing a second injection to achieve a satisfactory correction and then only seven ( 2.5 % ) in the rest . Level of evidence :", "PURPOSE To evaluate efficacy and safety of concurrent administration of 2 collagenase clostridium histolyticum ( CCH ) injections to treat 2 joints in the same h and with Dupuytren fixed flexion contractures ( FFCs ) . METHODS Patients with 2 or more contractures in the same h and caused by palpable cords participated in a 60-day , multicenter , open-label , phase 3b study . Two 0.58 mg CCH doses were injected into 1 or 2 cords in the same h and ( 1 injection per affected joint ) during the same visit . Finger extension was performed approximately 24 , 48 , or 72 or more hours later . Changes in FFC and range of motion , incidence of clinical success ( FFC ≤ 5 ° ) , and adverse events ( AEs ) were summarized . RESULTS The study enrolled 715 patients ( 725 treated joint pairs ) , and 714 patients ( 724 joint pairs ) were analyzed for efficacy . At day 31 , mean total FFC ( sum of 2 treated joints ) decreased 74 % , from 98 ° to 27 ° . Mean total range of motion increased from 90 ° to 156 ° . The incidence of clinical success was 65 % in metacarpophalangeal joints and 29 % in proximal interphalangeal joints . Most treatment-related AEs were mild to moderate , resolving without intervention ; the most common were swelling of treated extremity , contusion , and pain in extremity . The incidence of skin lacerations was 22 % ( 160 of 715 ) . Efficacy and safety were similar regardless of time to finger extension . CONCLUSIONS Collagenase clostridium histolyticum can be used to effectively treat 2 affected joints concurrently without a greater risk of AEs than treatment of a single joint , with the exception of skin laceration . The incidence of clinical success in this study after 1 injection per joint was comparable to phase 3 study results after 3 or more injections per joint . Two concurrent CCH injections may allow more rapid overall treatment of multiple affected joints , and the ability to vary the time between CCH injection and finger extension may allow physicians and patients greater flexibility with scheduling treatment", "PURPOSE The dem and for percutaneous needle fasciotomy ( PNF ) as treatment for Dupuytren 's disease is increasing because of its limited invasiveness , good outcome , limited number of complications , quick recovery , and overall patient satisfaction . This r and omized controlled trial was design ed to test whether these short-term expectations are sound by comparing this treatment with limited fasciectomy ( LF ) with regard to these aspects . METHODS We treated 166 rays : 88 by PNF and 78 by LF . Total passive extension deficit ( TPED ) improvement at 1 week and at 6 weeks were the primary outcome parameters ; patient satisfaction , h and -function recovery , and complication rate were secondary outcome parameters . We used the Disabilities of the Arm , Shoulder , and H and question naire to measure disabilities of the upper extremity before and after treatment and all adverse effects and complications were recorded . RESULTS Overall TPED improvement was best at 6 weeks . In the PNF group TPED improved by 63 % versus 79 % in the LF group ; this difference was statistically significant . Results at the proximal interphalangeal joint were worse than those at the metacarpophalangeal and distal interphalangeal joints for both the PNF and LF groups . The rays classified before surgery as Tubiana stages I and II showed no difference between these treatments , but for rays higher than stage II LF clearly was superior to PNF as a treatment modality . The rate of major complications in the LF group was 5 % versus 0 % in the PNF group . Patient satisfaction was almost equal but direct h and function after treatment was considered better in the PNF group , as was the degree of discomfort that patients experienced . This was underscored by the Disabilities of the Arm , Shoulder , and H and scores in the PNF group , which were significantly lower than those in the LF group at all time points measured . CONCLUSIONS In the short term and in cases with a TPED of 90 degrees or less PNF is a good treatment alternative to LF for treatment of Dupuytren 's disease . TYPE OF STUDY /LEVEL OF EVIDENCE Therapeutic , Level", "PURPOSE Collagenase Clostridium histolyticum ( CCH ) is approved for the treatment of adults with Dupuytren contracture with a palpable cord . This open-label , phase 4 study evaluated the safety and efficacy of CCH for the retreatment of recurrent contractures in joints that were previously effectively treated with CCH . METHODS Patients participating in a long-term follow-up study who had contracture recurrence ( increased ≥ 20 ° with a palpable cord ) after successful treatment in the previous study were eligible . Recurrent joint contractures were treated with up to 3 CCH injections ( ∼ 1 month apart ) . Patients were followed for 1 year to evaluate safety . Assessment s included change in joint contracture , range of motion , and the percentage of joints that achieved contracture of 5 ° or less at day 30 after the last injection . RESULTS The efficacy analysis included 51 patients with 1 treated joint per patient ( 31 metacarpophalangeal , 20 proximal interphalangeal ) . A total of 35 joints ( 69 % ) received 1 injection , 12 ( 24 % ) received 2 injections , and 4 ( 8 % ) received 3 injections . Fifty-seven percent of joints achieved contracture of 5 ° or less ( 29 of 51 ) . Overall , 86 % ( 43 of 50 ) patients had a 20 ° or greater increase in range of motion . The adverse event profile was consistent with previous studies . One ligament injury was reported . CONCLUSIONS At a short-term follow-up of 1 year , recurrent contracture in joints previously successfully treated with CCH may be effectively retreated with up to 3 injections of CCH . TYPE OF STUDY /LEVEL OF EVIDENCE Therapeutic IV", "PURPOSE The primary objective of this study was to quantify the degree of pain associated with collagenase Clostridium histolyticum ( CCH ) injection and to determine whether it is related to other factors in the intervention . METHODS A prospect i ve study of 135 patients was performed to evaluate pain at 3 points during treatment : ( 1 ) after CCH injection , using a numerical rating scale ( NRS ) , ( 2 ) a binary ( positive/negative ) assessment before manipulation 24 hours after CCH and after removing the b and age , and ( 3 ) after joint manipulation performed with wrist block anesthesia . RESULTS The average NRS for pain during infiltration was 4.7 . Pain was present before manipulation in 52.6 % of patients . Pain from manipulation showed an average NRS score of 3.6 . The amounts of pain at CCH infiltration , pain after 24 hours , and pain from the manipulation were correlated because patients who experienced pain during CCH infiltration were more likely to report experiencing pain during manipulation . CONCLUSIONS Collagenase Clostridium histolyticum injection for treating Dupuytren contracture can be a painful process . There is a clear relationship between a patient 's level of pain during injection of CCH and the likelihood that the patient will experience pain during manipulation , even with the use of local anesthesia . TYPE OF STUDY /LEVEL OF EVIDENCE Prognostic IV", "INTRODUCTION The purpose of this study was to compare the cost of treatment of Dupuytren 's disease , ganglia and trigger digits in the out-patient department with the operating theatre . PATIENTS AND METHODS All patients seen in a new patient h and clinic with a diagnosis of Dupuytren 's disease , trigger digit or ganglion of the wrist or h and requiring treatment were prospect ively identified over a 6-month period . The numbers undergoing a procedure in the out-patient clinic or theatre were recorded . Costings of theatre time and out-patient time , as well as national tariff income , were obtained from the hospital management . RESULTS Over the 6-month period , 80 , 26 , and 52 patients were treated with regard to Dupuytren 's disease , ganglia and trigger digits , respectively . Of these , 37 , 23 , and 44 were treated by an out-patient procedure , and 43 , 3 and 8 underwent a formal operation . The total cost of the out-patient procedures was calculated at pound 1560 over 6 months . To perform these as formal operations would have cost pound 64,896 . The cost savings were , therefore , pound 63,336 , or pound 126,672 per annum . CONCLUSIONS Out-patient interventions for Dupuytren 's disease , ganglia and trigger digits result in significant cost savings over formal surgical treatment ", "Dupuytren ’s disease is an affliction of the palmar fascia . Selective fasciectomy is recommended once contracture has occurred . Alternatives for wound closure include tissue rearrangement , the open palm technique , and full-thickness skin grafting . In this prospect i ve study , a new “ synthesis ” technique was used to treat a cohort of patients with advanced Dupuytren ’s disease . The results were then compared with those of a second cohort of patients who underwent the open palm technique . Thirty consecutive patients were selected . Ten patients ( nine men and one woman ; average age , 67 years ) underwent the open palm technique , and 20 patients ( 18 men and two women ; average age , 70 years ) underwent the synthesis method . Follow-up was 3.5 years for the open palm group and 2.7 years for the synthesis group . All patients in both groups improved with respect to motion , function , appearance , and satisfaction . Objective ly , for the open palm technique , metacarpophalangeal joint contracture decreased from 50 degrees to 0 degrees , and proximal interphalangeal joint contracture decreased from 40 degrees to 6 degrees . Using the synthesis method , metacarpophalangeal joint contracture decreased from 57 degrees to 0 degrees , and proximal interphalangeal joint contracture decreased from 58 degrees to 10 degrees . The Disabilities of the Arm , Shoulder , and H and Test scores decreased from 37 to 30 in both groups . There were no significant differences between groups in these parameters . The two significant intergroup differences were healing time ( 40 days for the open palm technique versus 28 days for the synthesis method ) and recurrence rate ( 50 percent for open palm versus 0 percent for synthesis ) . The synthesis technique combines with success the best features of current methods for the surgical treatment of advanced Dupuytren ’s disease", "Whether the palmar skin has a role in the development , propagation or recurrence of Dupuytren ’s disease remains unclear . Clinical assessment for skin involvement is difficult and its correlation with histology uncertain . We prospect ively biopsied the palmar skin of consecutive patients undergoing single digit fasciectomy ( for primary Dupuytren ’s disease without clinical ly involved skin ) and dermofasciectomy ( for clinical ly involved skin or recurrence ) in order to investigate this relationship . We found dermal fibromatosis in 22 of 44 patients ( 50 % ) undergoing fasciectomy and 41 of 59 patients ( 70 % ) undergoing dermofasciectomy . Dermal fibromatosis appeared to be associated with greater preoperative angular deformity , presence of palmar nodules and occupations involving manual labour . Dermal fibromatosis exists in the absence of clinical features of skin involvement and we hypothesize that the skin may have a greater role in the development and propagation of Dupuytren ’s disease than previously thought . Level of evidence :" ]	4118892a-06ff-11f0-808a-c43d1ab1c353
Skeletal muscle atrophy is a major systemic impairment in chronic diseases . Yet its determinants have been hard to identify because a clear research definition has not been agreed upon . The reduction in muscle fiber cross-sectional area ( CSA ) is a widely acknowledged marker of muscle atrophy , but no reference values for the muscle fiber CSA at the age of the onset of chronic disease have ever been published . Thus , we aim ed to systematic ally review the studies providing data on fiber CSA and fiber type proportion in the vastus lateralis of the quadriceps of healthy subjects ( age > 40 yr ) and then to pool and analyze the data from the selected studies to determine reference values for fiber CSA . We followed the guidelines of the Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) and identified 19 studies , including 423 subjects that matched the inclusion criteria . On the basis of fiber type and gender , the mean fiber CSA and the lower limits of normal ( LLNs ) were ( % type I60 ) + 1,743 μm(2 ) and ( % type I60 ) - 718 μm(2 ) , respectively , for men ; and ( % type I70 ) + 139 μm(2 ) and ( % type I70 ) - 1,485 μm(2 ) , respectively , for women . There was no significant heterogeneity among subgroups of fiber type and gender . The pooled type I fiber proportion was 50.3 % ( LLN = 32.9 % ) . In multivariate analysis , fiber CSA was significantly correlated with Vo2 peak ( r = 190.92 ; P = 0.03 ) , and type I fiber proportion was correlated with age ( r = -0.024 ; P = 0.005 ) , body mass index ( r = 0.096 ; P = 0.005 ) , and Vo2 peak ( r = -0.053 ; P = 0.005 ) . Our meta analysis of a homogeneous set of studies is the first to provide valuable LLNs for fiber CSA according to fiber type and gender . This analysis will be improved by prospect i ve assessment in well-characterized healthy subjects	[ "The study of the peripheral skeletal muscle function in patients with chronic obstructive pulmonary disease ( COPD ) is of growing interest , but often requires biopsies , usually with the Bergström technique . The current study was design ed to test the validity of a minimally invasive technique : the microbiopsy . In 17 patients with COPD and four normal subjects , two specimens of the vastus lateralis were taken percutaneously under local anaesthesia , one with a 16-gauge needle ( microbiopsy ) and the other with the Bergström needle . The enzymatic activity of citrate synthase ( CS ) and phosphofructokinase ( PFK ) , and the myosin heavy chain ( MyoHC ) composition were measured for both techniques . The subjects reported no pain or much less with the microbiopsy compared with the Bergström biopsy . The microbiopsy sample weight reached 55±17 mg . The two techniques showed excellent agreement for CS activity and MyoHC composition . The PFK activity did not differ statistically between the techniques , but the agreement was moderate . The agreement between both biopsy techniques was stable over time . The median ( range ) fibre number within the microbiopsy specimens was 144 ( 38–286 ) . In conclusion , the current study shows the feasibility and validity of a minimally invasive muscle biopsy technique that appears more comfortable for subjects , compared with the Bergström technique ", "Muscle dysfunction is a major problem in chronic obstructive pulmonary disease ( COPD ) , particularly after exacerbations . We thus asked whether neuromuscular electrostimulation ( NMES ) might be directly useful following an acute exacerbation and if such a therapy decreases muscular oxidative stress and /or alters muscle fibre distribution . A pilot r and omised controlled study of NMES lasting 6 weeks was carried out in 15 in- patients ( n=9 NMES ; n=6 sham ) following a COPD exacerbation . Stimulation was delivered to the quadriceps and hamstring muscles ( 35 Hz ) . Primary outcomes were quadriceps force and muscle oxidative stress . At the end of the study , quadriceps force improvement was statistically different between groups ( p=0.02 ) , with a significant increase only in the NMES group ( median ( interquartile range ) 10 ( 4.7–11.5 ) kg ; p=0.01 ) . Changes in the 6-min walking distance were statistically different between groups ( p=0.008 ) , with a significant increase in the NMES group ( 165 ( 125–203 ) m ; p=0.003 ) . NMES did not lead to higher muscle oxidative stress , as indicated by the decrease in total protein carbonylation ( p=0.02 ) and myosin heavy chain carbonylation ( p=0.01 ) levels . Finally , we observed a significant increase in type I fibre proportion in the NMES group . Our study shows that following COPD exacerbation , NMES is effective in counteracting muscle dysfunction and decreases muscle oxidative stress", "Nine African and eight Caucasian 10-km runners resident at sea level volunteered . Maximal O2 consumption and peak treadmill velocity ( PTV ) were measured by using a progressive test , and fatigue resistance [ time to fatigue ( TTF ) ] was measured by using a newly developed high-intensity running test : 5 min at 72 , 80 , and 88 % of individual PTV followed by 92 % PTV to exhaustion . Skeletal muscle enzyme activities were determined in 12 runners and 12 sedentary control subjects . In a comparison of African and Caucasian runners , mean 10-km race time , maximal O2 consumption , and PTV were similar . In African runners , TTF was 21 % longer ( P plasma lactate accumulation after 5 min at 88 % PTV was 38 % lower ( P citrate synthase activity was 50 % higher ( 27.9 + /- 7.5 vs. 18.6 + /- 2.1 micromol . g wet wt-1 . min-1 , P = 0.02 ) . Africans accumulated lactate at a slower rate with increasing exercise intensity ( P citrate synthase activity was associated with a longer TTF ( r = 0.70 , P plasma lactate accumulation ( r = -0.73 , P = 0.01 ) , and a lower respiratory exchange ratio ( r = -0.63 , P African and Caucasian runners in the present study differed with respect to oxidative enzyme activity , rate of lactate accumulation , and their ability to sustain high-intensity endurance exercise", "CONTEXT Even though the strong association between physical inactivity and ill health is well documented , 60 % of the population is inadequately active or completely inactive . Traditional methods of prescribing exercise have not proven effective for increasing and maintaining a program of regular physical activity . OBJECTIVE To compare the 24-month intervention effects of a lifestyle physical activity program with traditional structured exercise on improving physical activity , cardiorespiratory fitness , and cardiovascular disease risk factors . DESIGN R and omized clinical trial conducted from August 1 , 1993 , through July 31 , 1997 . PARTICIPANTS Sedentary men ( n = 116 ) and women ( n = 119 ) with self-reported physical activity of less than 36 and 34 kcal/kg per day , respectively . INTERVENTIONS Six months of intensive and 18 months of maintenance intervention on either a lifestyle physical activity or a traditional structured exercise program . MAIN OUTCOME MEASURES Primary outcomes were physical activity assessed by the 7-Day Physical Activity Recall and peak oxygen consumption ( VO2peak ) by a maximal exercise treadmill test . Secondary outcomes were plasma lipid and lipoprotein cholesterol concentrations , blood pressure , and body composition . All measures were obtained at baseline and at 6 and 24 months . RESULTS Both the lifestyle and structured activity groups had significant and comparable improvements in physical activity and cardiorespiratory fitness from baseline to 24 months . Adjusted mean changes ( 95 % confidence intervals [ CIs ] ) were 0.84 ( 95 % CI , 0.42 - 1.25 kcal/kg per day ; P activity , and 0.77 ( 95 % CI , 0.18 - 1.36 mL/kg per minute ; P = .01 ) and 1.34 ( 95 % CI , 0.72 - 1.96 mL/kg per minute ; P VO2peak for the lifestyle and structured activity groups , respectively . There were significant and comparable reductions in systolic blood pressure ( -3.63 [ 95 % CI , -5.54 to -1.72 mm Hg ; P diastolic blood pressure ( -5.38 [ 95 % CI , -6.90 to -3.86 mm Hg ; P lifestyle and structured activity groups , respectively . Neither group significantly changed their weight ( -0.05 [ 95 % CI , -1.05 to 0.96 kg ; P = .93 ] and 0.69 [ 95 % CI , -0.37 to 1.74 kg ; P = .20 ] ) , but each group significantly reduced their percentage of body fat ( -2.39 % [ 95 % CI , -2.92 % to -1.85 % ; P structured activity groups , respectively . CONCLUSIONS In previously sedentary healthy adults , a lifestyle physical activity intervention is as effective as a structured exercise program in improving physical activity , cardiorespiratory fitness , and blood pressure", "There are conflicting reports of the effects of hormone replacement therapy ( HRT ) on strength preservation in postmenopausal women , while any effect on power output has received little attention . Decreased steadiness of force generation has been reported in older muscles and may be related to the hormonal changes associated with the menopause , but the effect of HRT has not been investigated . We have studied the effect of HRT on strength , power output and isometric force steadiness in healthy women . Sixteen young ( aged 27.4±1.4 years , mean ± SEM ) and 29 postmenopausal women were studied . Fifteen of the latter were taking HRT ( 68.1±1.4 years , HRT+ ) and 14 ( 70.5±1.5 years , HRT− ) had never done so . During isometric quadriceps contractions the force steadiness ( coefficient of variation of force ) was measured at 10 , 25 , 50 and 100 % maximum voluntary contraction ( MVC ) . The average power generated by an explosive leg extension was recorded . The HRT− group generated less power ( 110.2±7.2 W ) than both the HRT+ ( 136.5±10.9 W , P=0.027 ) and young ( 136.2±5.8 W , P=0.027 ) subjects . Power output was similar in the HRT+ and younger subjects . The HRT− subjects were weaker than the younger ones ( 241.3±14.0 N vs. 297.6±13 N , P=0.006 ) . The strength of the HRT+ group ( 255.5±14 N ) was not significantly different to the other two groups . There was no difference in steadiness between the three groups at any of the force levels . HRT appears to maintain power output to a greater extent than isometric strength in postmenopausal women . There was no evidence for an effect of either age or HRT on isometric steadiness in the quadriceps", "The goal of this study was to use the model of spinal cord isolation ( SI ) , which blocks nearly all neuromuscular activity while leaving the motoneuron muscle-fiber connections intact , to characterize the cellular processes linked to marked muscle atrophy . Rats r and omly assigned to normal control and SI groups were studied at 0 , 2 , 4 , 8 , and 15 days after SI surgery . The slow soleus muscle atrophied by approximately 50 % , with the greatest degree of loss occurring during the first 8 days . Throughout the SI duration , muscle protein concentration was maintained at the control level , whereas myofibrillar protein concentration steadily decreased between 4 and 15 days of SI , and this was associated with a 50 % decrease in myosin heavy chain ( MHC ) normalized to total protein . Actin relative to the total protein was maintained at the control level . Marked reductions occurred in total RNA and DNA content and in total MHC and actin mRNA expressed relative to 18S ribosomal RNA . These findings suggest that two key factors contributing to the muscle atrophy in the SI model are 1 ) . a reduction in ribosomal RNA that is consistent with a reduction in protein translational capacity , and 2 ) . insufficient mRNA substrate for translating key sarcomeric proteins comprising the myofibril fraction , such as MHC and actin . In addition , the marked selective depletion of MHC protein in the muscles of SI rats suggests that this protein is more vulnerable to inactivity than actin protein . This selective MHC loss could be a major contributor for the previously reported loss in the functional integrity of SI muscles . Collectively , these data are consistent with the involvement of pretranslational and translational processes in muscle atrophy due to SI", "Objective : Muscle weakness contributes to prolonged rehabilitation and adverse outcome of critically ill patients . Distinction between a neurogenic and /or myogenic underlying problem is difficult using routine diagnostic tools . Preferential loss of myosin has been suggested to point to a myogenic component . We evaluated markers of muscle atrophy and denervation , and the myosin/actin ratio in limb and abdominal wall skeletal muscle of prolonged critically ill patients and matched controls in relation to insulin therapy and known risk factors for intensive care unit-acquired weakness . Design : Secondary analysis of two large , prospect i ve , single-center r and omized clinical studies . Setting : University hospital surgical and medical intensive care unit . Patients : Critically ill patients and matched controls . Interventions : Intensive care unit patients had been r and omized to blood glucose control to 80–110 mg/dL with insulin infusion or conventional glucose management , where insulin was only administered when glucose levels rose above 215 mg/dL. Measurements and Main Results : As compared with controls , rectus abdominis and vastus lateralis muscle of critically ill patients showed smaller myofiber size , decreased mRNA levels for myofibrillar proteins , increased proteolytic enzyme activities , and a lower myosin/actin ratio , virtually irrespective of insulin therapy . Increased forkhead box O1 action may have played a role . Most alterations were more severe in patients treated with corticosteroids . Duration of corticosteroid treatment , independent of duration of intensive care unit stay or other risk factors , was a dominant risk factor for a low myosin/actin ratio . The immature acetylcholine receptor subunit & ggr ; messenger RNA expression was elevated in vastus lateralis , independent of the myosin/actin ratio . Conclusions : Both limb and abdominal wall skeletal muscles of prolonged critically ill patients showed downregulation of protein synthesis at the gene expression level as well as increased proteolysis . This affected myosin to a greater extent than actin , result ing in a decreased myosin/actin ratio . Muscle atrophy was not ameliorated by intensive insulin therapy , but possibly aggravated by corticosteroids", "Abstract Objective To determine whether poor reporting of methods in r and omised controlled trials reflects on poor methods . Design Observational study . Setting Reports of r and omised controlled trials conducted by the Radiation Therapy Oncology Group since its establishment in 1968 . Participants The Radiation Therapy Oncology Group . Outcome measures Content of reports compared with the design features described in the protocol s for all r and omised controlled trials . Results The method ological quality of 56 r and omised controlled trials was better than reported . Adequate allocation concealment was achieved in all trials but reported in only 42 % of papers . An intention to treat analysis was done in 83 % of trials but reported in only 69 % of papers . The sample size calculation was performed in 76 % of the studies , but reported in only 16 % of papers . End points were clearly defined and α and βerrors were prespecified in 76 % and 74 % of the trials , respectively , but only reported in 10 % of the papers . The one exception was the description of drop outs , where the frequency of reporting was similar to that contained in the original statistical files of the Radiation Therapy Oncology Group . Conclusions The reporting of method ological aspects of r and omised controlled trials does not necessarily reflect the conduct of the trial . Review ing research protocol s and contacting trialists for more information may improve quality assessment", "R and omized clinical trial ( RCT ) publications with inappropriate r and om-sequence generation , lack of allocation concealment , or imperfect blinding yield inflated estimates of effect compared to those in which adequate methods are described . RCTs that do not state methods used yield similar effect estimates , suggesting that inadequate methods were used . We compared RCT publications with investigator reports of actual practice for 40 rheumatology RCTs published in 1997/1998 . In RCTs in which these methods were not described in the trial reports and would thus have been characterized as \" inadequate , \" investigators reported using methods of r and om-sequence generation and allocation concealment that would be considered adequate in 77.4 and 78.1 % of RCTs , respectively . This suggests that , in contrast to previous reports , inadequate r and om-sequence generation and allocation concealment , per se , may not be a major problem in RCTs . Characterizing RCTs as \" good \" or \" poor \" quality based on the published report is likely to be inappropriate", "To obtain normative muscle morphology data on a healthy population recruited from a population survey , we examined vastus lateralis biopsies from 58 men and 33 women , aged 26 - 67 years . Biopsies were measured with automated , computer-aided techniques . Data were analyzed according to gender and age , and the influence of blood pressure , body mass index ( BMI ) , and smoking habits was also examined . Men had larger muscle fibers ( fiber area approximately 5400 microm(2 ) ) than women ( approximately 4000 microm(2 ) , P = 0.003 ) . No gender differences were seen in fiber composition , fiber roundness , percentage of connective tissue , or capillary density . Blood pressure did not influence fiber size or composition , but was correlated with fiber roundness in men . BMI was associated with fiber area in men , but not in women . Variations in age , smoking habits , and physical activity did not influence muscle morphology data substantially . Thus , in a normal population , men have larger muscle fibers than women , but similar fiber composition . Variation in gender , BMI , blood pressure , and physical activity may influence morphological features to a minor degree", "OBJECTIVE Muscle fiber characteristics are altered in type 2 diabetes . We studied whether these alterations also exist in impaired glucose tolerance ( IGT ) and whether they are determinants of insulin sensitivity and glucose tolerance in postmenopausal women . RESEARCH DESIGN AND METHODS Percutaneous muscle biopsies from the vastus lateralis muscle were obtained from 77 postmenopausal women aged 57 - 59 years : 50 women with normal glucose tolerance ( NGT ) and 27 with IGT . The IGT group had a reduced insulin sensitivity compared with the NGT group ( euglycemic-hyperinsulinemic clamp ) ( P = 0.003 ) . RESULTS The groups did not differ in muscle fiber composition , as judged by the percentage of type I , IIa , or IIx fibers . In contrast , the IGT group had increased size of the IIa ( mean + /-SD 3,776+/-987 vs. 3,078+/-862 microm2 , P = 0.002 ) and IIx fibers ( 2,730+/-1,037 vs. 2,253+/-672 microm2 , P = 0.017 ) . There was a trend for the capillary diffusion areas ( the muscle area supplied by each capillary ) to be larger in the IGT group for the IIa ( 1,132+/-286 vs. 1,013+/-240 microm2 , P = 0.061 ) and IIx fibers ( 1,020+/-246 vs. 906+/-240 microm2 , P = 0.058 ) . In the entire group , insulin sensitivity correlated with the size of the type IIa fibers ( r = -0.28 , P = 0.013 ) , but not with the percentages of muscle fiber types . In a multiple regression , insulin sensitivity was determined by body fat content and HDL cholesterol level , while the size of the IIa fibers was not included in the model . Glucose tolerance was independently predicted by the number of capillaries/type I fiber , as well as by insulin sensitivity and triglyceride levels . CONCLUSIONS We conclude that although muscle fiber composition is not altered , women with IGT have larger type IIa and IIx muscle fibers and a trend for increased capillary diffusion areas for these fibers , compared with women with NGT . In the entire group , insulin sensitivity was determined mainly by body fat content , while muscle fiber capillarization may be of importance for glucose tolerance" ]	41188966-06ff-11f0-808a-c43d1ab1c353
OBJECTIVES Older head and neck cancer patients are at increased risk for adverse health outcomes , but little is known about which geriatric assessment associates with poor outcome . The aim is to study the association of functional or cognitive impairment , social environment and frailty with adverse health outcomes in patients with head and neck cancer . METHODS Four libraries were search ed for studies reporting on an association of functional or cognitive impairment , social environment and frailty with adverse outcomes in head and neck cancer patients . RESULTS Of 4158 identified citations , 31 articles were included . The mean age was ⩾60years in twelve studies ( 39 % ) . Geriatric conditions were prevalent : between 40 and 50 % of the included participants were functional impaired , around 50 % had depressive symptoms , and around 40 % did not have a partner . Functional impairment was assessed in 18 studies , two studies reported on a cognitive test , eight studies examined mood and social status was depicted by 14 studies . None of the included studies addressed frailty or objective ly measured physical capacity such as h and grip strength , gait speed or balance tests . In 64 % of the reported associations , a decline in functional or cognitive impairment , mood or social environment was associated with adverse outcomes . CONCLUSION Functional and cognitive impairment , depressive symptoms and social isolation are highly prevalent in head and neck cancer patients and associate with high risk of adverse health outcomes . In the future , these measurements may guide decision-making and customize treatments , but more research is needed to further improve and firmly establish clinical usability	[ "OBJECTIVES To characterize and compare quality of life ( QOL ) in patients with head and neck cancer shortly before initial treatment and 1 year later and to study the predictors of changes in QOL over 1 year . DESIGN Prospect i ve cohort study . SETTING Three otolaryngology clinics . PATIENTS Three hundred sixteen patients having newly diagnosed squamous cell head and neck cancer . MAIN OUTCOME MEASURE Health-related QOL was assessed using the 36-item Short-Form Health Survey and a head and neck cancer-specific QOL scale . RESULTS Over 1 year , QOL decreased for physical functioning measures and eating but improved for mental health QOL . Depression and smoking were major predictors of poor QOL at baseline . Major predictors of change in QOL from baseline to 1 year were treatment factors , especially feeding tube placement ( 9 scales ) , chemotherapy ( 3 scales ) , and radiation therapy ( 3 scales ) . Baseline smoking and depressive symptoms also remained significant predictors of several QOL scales at 1 year . CONCLUSIONS Health-related physical QOL tended to decline over 1 year and mental health QOL improved . The major predictors of change in QOL were treatment factors , smoking , and depressive symptoms . Physicians should alert patients to the relative effects on QOL one may experience with different treatments", "BACKGROUND Early discontinuation of adjuvant endocrine therapy may affect the outcome of treatment in breast cancer patients . The aim of this study was to assess age-specific persistence and age-specific survival outcome based on persistence status . METHODS Patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational trial were included . Nonpersistence was defined as discontinuing the assigned endocrine treatment within 1 year of follow-up because of adverse events , intercurrent illness , patient refusal , or other reasons . Endpoints were the breast cancer-specific and overall survival times . Analyses were stratified by age at diagnosis ( , 65 - 74 years , ≥75 years ) . RESULTS Overall , 3,142 postmenopausal breast cancer patients were included : 1,682 were aged Older age was associated with a higher proportion of nonpersistence within 1 year of follow-up . In patients aged lower breast cancer-specific and overall survival probabilities . In patients aged 65 - 74 years and patients aged ≥75 years , the survival times of persistent and nonpersistent patients were similar . CONCLUSION Nonpersistence within 1 year of follow-up was associated with lower breast cancer-specific and overall survival probabilities in patients aged associated with survival outcomes in patients aged 65 - 74 years or in patients aged ≥75 years . These results suggest that extrapolation of outcomes from a young to an elderly breast cancer population may be insufficient and urge age-specific breast cancer studies", "Background : There is no single generally accepted clinical definition of frailty . Previously developed tools to assess frailty that have been shown to be predictive of death or need for entry into an institutional facility have not gained acceptance among practising clinicians . We aim ed to develop a tool that would be both predictive and easy to use . Methods : We developed the 7-point Clinical Frailty Scale and applied it and other established tools that measure frailty to 2305 elderly patients who participated in the second stage of the Canadian Study of Health and Aging ( CSHA ) . We followed this cohort prospect ively ; after 5 years , we determined the ability of the Clinical Frailty Scale to predict death or need for institutional care , and correlated the results with those obtained from other established tools . Results : The CSHA Clinical Frailty Scale was highly correlated ( r = 0.80 ) with the Frailty Index . Each 1-category increment of our scale significantly increased the medium-term risks of death ( 21.2 % within about 70 mo , 95 % confidence interval [ CI ] 12.5%–30.6 % ) and entry into an institution ( 23.9 % , 95 % CI 8.8%–41.2 % ) in multivariable models that adjusted for age , sex and education . Analyses of receiver operating characteristic curves showed that our Clinical Frailty Scale performed better than measures of cognition , function or comorbidity in assessing risk for death ( area under the curve 0.77 for 18-month and 0.70 for 70-month mortality ) . Interpretation : Frailty is a valid and clinical ly important construct that is recognizable by physicians . Clinical judgments about frailty can yield useful predictive information", "Objectives To quantify the proportion of r and omized controlled trials ( RCTs ) specifically design ed for elderly , and to assess their characteristics , as compared to RCTs not specifically design ed for elderly . Design Review and synthesis of published literature . Measurements We search ed PubMed for articles published in the year 2012 . We included RCTs . Articles were excluded if not conducted with human subjects or if findings of secondary analyses were reported . A r and om sample of 10 % was drawn and of this selection the following trial characteristics were extracted : sample size , disease category , age of sample , and age-related inclusion criteria . Clinical trials were defined to be specifically design ed for elderly if a lower age cut-off of ≥ 55 years was used , or when participants had an average age of ≥ 70 years . Results The search strategy yielded 26,740 articles , from which a r and om sample was drawn , result ing in 2375 articles . After exclusion , data was extracted from 1369 publications . Of these 1369 RCTs , 96 ( 7 % ) were specifically design ed for elderly . In comparison with trials not design ed for older adults , trials design ed for elderly contained a significantly larger median number of participants ( 125 vs. 80 , p = 0.008 ) significantly more trials design ed for elderly fell into the disease categories eye ( 6 % vs. 2 % , p = 0.005 ) , musculoskeletal ( 13 % vs. 7 % , p = 0.023 ) and circulatory system ( 16 % vs. 9 % , p = 0.039 ) . No significant difference was observed with regard to the other disease categories . Conclusion There is a low proportion of RCTs specifically design ed for elderly . As older patients will increasingly form the majority in medical practice , there is an urgent need for stronger evidence for the formulation of treatment guidelines specifically for older adults", "Objective The aim of this study was to identify risk factors for surgical-site infections ( SSIs ) in patients with head and neck cancer su bmi tted to major clean-contaminated surgery . Study Design This is a prospect i ve study conducted in a tertiary cancer center hospital . Subjects and Methods This study includes 258 patients su bmi tted to a major clean-contaminated head and neck oncologic surgery . Results The overall SSI rate was 38.8 % . The univariate analysis showed the following significant risk factors : race , tobacco consumption , clinical stage , comorbidities , time duration of the surgical procedure , and flap reconstruction . The final model by logistic regression identified the following independent predictors for SSI : tobacco consumption ( odds ratio [ OR ] = 2.96 ) , presence of metastatic lymph nodes ( OR = 2.05 ) , flap reconstruction ( OR = 2.20 ) , and antimicrobial prophylaxis exceeding 48 hours ( OR=1.89 ) . Conclusion The high-risk patients for SSI in head and neck oncologic surgery were those with cancer at advanced stages , those who were smokers , those presenting comorbidities , those who needed major reconstruction of the surgical wound , or those who were su bmi tted to inadequate antibiotic prophylaxis", "OBJECTIVE To evaluate the association between pretreatment health-related quality -of-life ( HRQOL ) scores and survival in a heterogeneous cohort of patients with newly diagnosed head and neck squamous cell carcinoma ( HNSCC ) . DESIGN Prospect i ve cohort study . SETTING University hospital and referral center in Western Norway . PATIENTS A total of 106 patients with intact cognitive functioning who were younger than 78 years , were diagnosed as having HNSCC , and underwent treatment with curative intent from November 1 , 2002 , through June 30 , 2005 . MAIN OUTCOME MEASURES Overall survival and HRQOL scores obtained at the time of diagnosis . RESULTS All dichotomized HRQOL sum scores except the functional score ( P = .20 ) were significantly predictive of survival in univariate analyses . The hazard ratios of the dichotomized general symptom , global quality -of-life , and head and neck sum score were 3.66 , 0.31 , and 2.28 , respectively . All sum scores except the dichotomized functional score remained predictive of survival after sequential adjustment for sociodemographic and clinical characteristics , neuroticism , choice of psychological coping , current smoking and alcohol consumption , and comorbidities . Similar findings were found for specific HRQOL indices of physical functioning , dyspnea , sleep disturbance , appetite loss , swallowing , and social eating from the European Organization for Research and Treatment of Cancer 30-Item Core Quality of Life Question naire , version 3.0 , and the Quality of Life-Head and Neck Cancer Module . Moreover , patients in the highest scoring quartiles for the symptom sum scores and /or the lowest scoring quartile for the global score had overall mortality rates of 50 % to 64 % compared with 23 % to 26 % among the other patients . CONCLUSION The HRQOL sum scores and specific indices among HNSCC patients predict survival independently of established known prognostic factors", "Background Head and neck cancer ( HNC ) is a debilitating disease due in part to its effects on function , including speech , swallowing , and cosmesis . Previous studies regarding depression in HNC have focused on demographic predictors , incidence , and quality of life studies . There is , however , a paucity of studies that objective ly address depressive symptoms in HNC patients and the result ant effects on post-treatment functional performance status . The aim of this study was to assess the relationship between preoperative depressive symptoms ( PDS ) and postoperative functional performance status ( PFPS ) , in addition to other predictors of rehabilitation and survival . Methods A prospect i ve cohort study was undertaken at the University of Alberta , including all new adult HNC patients undergoing surgery as primary therapy for HNC from May 2013 to January 2014 . Baseline depressive symptoms were measured on the Quick Inventory of Depressive Symptoms ( QIDS ) question naire 2 weeks preoperatively and PFPS was assessed 12 months postoperatively on the Functional Assessment of Cancer Therapy-Head & Neck ( FACT-HN ) scale . Secondary outcomes included completion of adjuvant therapy , narcotic dependence , return to detrimental habits , loss of follow-up , and length of hospital stay ( LOHS ) . Differences between the Normal-Mild and Moderate-Severe QIDS groups were assessed using Mann – Whitney and Fischer Exact statistical analyses . Results Seventy-one patients were included in the study . Mild and Moderate-Severe PDS were 35.2 % and 18.3 % , respectively . Significantly lower FACT-HN scores were noted in the Moderate-Severe group at 12 months ( p = 0.03 ) . The risk ratio ( RR ) for FACT-HN score completion of adjuvant treatment ( p = 0.03 ) , significantly higher incidence of narcotic dependence ( p = 0.004 ) , and significantly higher LOHS ( 24 days vs. 18 days ; p = 0.02 ) was observed in the Moderate-Severe group . There was no significant difference in loss of follow-up between the 2 groups ( p = 0.64 ) . Conclusions The incidence and severity of PDS in HNC patients treated with surgery is high ( 53.5 % ) . Patients with Moderate-Severe PDS have significantly decreased PFPS , increased narcotic use , decreased completion of adjuvant therapy , and a longer LOHS . HNC patients should be monitored closely for depressive symptoms", "OBJECTIVE To examine the association between the outcomes of a pre-operative comprehensive geriatric assessment ( CGA ) and the risk of severe post-operative complications in elderly patients electively operated for colorectal cancer . METHODS One hundred seventy-eight consecutive patients ≥ 70 years electively operated for all stages of colorectal cancer were prospect ively examined . A pre-operative CGA was performed , and patients were categorized as fit , intermediate , or frail . The main outcome measure was severe complications within 30 days of surgery . RESULTS Twenty-one patients ( 12 % ) were categorized as fit , 81 ( 46 % ) as intermediate , and 76 ( 43 % ) as frail . Eighty-three patients experienced severe complications , including three deaths ; 7/21 ( 33 % ) of fit patients , 29/81 ( 36 % ) of intermediate patients and 47/76 ( 62 % ) of frail patients ( p=0.002 ) . Increasing age and ASA classification were not associated with complications in this series . CONCLUSION CGA can identify frail patients who have a significantly increased risk of severe complications after elective surgery for colorectal cancer", "It has been hypothesized that people in lower socioeconomic groups have worse outcomes because they present with advanced‐stage cancers or receive inadequate treatment . The authors investigated this hypothesis by using education level as a proxy for socioeconomic status in patients treated on Radiation Therapy Oncology Group ( RTOG ) Protocol 90‐03", "PURPOSE To analyze the prospect ively collected health-related quality -of-life ( HRQOL ) data from patients enrolled in two Radiation Therapy Oncology Group r and omized Phase III head and neck cancer trials ( 90 - 03 and 91 - 11 ) to assess their value as an independent prognostic factor for locoregional control ( LRC ) and /or overall survival ( OS ) . METHODS AND MATERIAL S HRQOL question naires , using a vali date d instrument , the Functional Assessment of Cancer Therapy-Head and Neck ( FACT-H&N ) , version 2 , were completed by patients before the start of treatment . OS and LRC were the outcome measures analyzed using a multivariate Cox proportional hazard model . RESULTS Baseline FACT-H&N data were available for 1,093 patients and missing for 417 patients . No significant difference in outcome was found between the patients with and without baseline FACT-H&N data ( p = 0.58 ) . The median follow-up time was 27.2 months for all patients and 49 months for surviving patients . Multivariate analyses were performed for both OS and LRC . Beyond tumor and nodal stage , Karnofsky performance status , primary site , cigarette use , use of concurrent chemotherapy , and altered fractionation schedules , the FACT-H&N score was independently predictive of LRC ( but not OS ) , with p = 0.0038 . The functional well-being component of the FACT-H&N predicted most significantly for LRC ( p = 0.0004 ) . CONCLUSIONS This study represents , to our knowledge , the largest analysis of HRQOL as a prognostic factor in locally advanced head and neck cancer patients . The results of this study have demonstrated the importance of baseline HRQOL as a significant and independent predictor of LRC in patients with locally advanced head and neck cancer", "OBJECTIVE Symptoms of depression are common in those with cancer . The authors investigated whether depressive symptoms assessed before the initiation of cancer treatment predicted diminished health-related quality of life ( HRQOL ) at follow-up . DESIGN As part of a large , prospect i ve study of oncologic outcomes , 306 patients with head and neck cancer ( HNC ) were assessed on several clinical and psychosocial characteristics during a pretreatment clinic visit and then at 3- and 12-month follow-up appointments . MAIN OUTCOME MEASURES Depressive symptomatology was assessed with the Beck Depression Inventory and HNC-specific HRQOL ( main outcome measure ) was assessed with the Head and Neck Cancer Inventory . RESULTS Controlling for age , gender , marital status , cancer site , stage of disease , alcohol and tobacco use , comorbidity status , and pretreatment HRQOL , simultaneous multiple regression analyses revealed that depressive symptoms present at study enrollment , before the initiation of cancer treatment , significantly predicted lower HRQOL at 3- and 12-month follow-up assessment s across the 4 HNC-specific domains of speech , eating , aesthetics , and social disruption ( all ps HNC survivors . Thus , it may be useful to assess depression at diagnosis to identify individuals at greater risk for poor HRQOL outcomes", "PURPOSE Death from noncancer causes ( competing mortality ) is an important event in head and neck cancer , but studies identifying predictors of this event are lacking . We sought to identify predictors of competing mortality and develop a risk stratification model for competing events . PATIENTS AND METHODS Cohort study of 479 patients with stage III to IV carcinoma of the head and neck diagnosed between August 1993 and November 2004 . Patients were treated on consecutive prospect i ve clinical trials involving organ-preserving chemoradiotherapy and surgery . We used multivariable competing risks regression models to analyze factors associated with the cumulative incidence of competing mortality , locoregional and distant failure , and second malignancies as first events . Results Median follow-up was 52 months median for survivors . The 5-year cumulative incidence of competing mortality was 19.6 % ( 95 % CI , 15.8 to 23.4 ) . On multivariable analysis , competing mortality was associated with female sex ( hazard ratio [ HR ] , 1.72 ; 95 % CI , 1.13 to 2.63 ) , increasing age ( HR , 1.30 ; 95 % CI , 1.04 to 1.62 ) , increasing Charlson Comorbidity Index ( HR , 1.24 ; 95 % CI , 1.05 to 1.47 ) , decreasing body mass index ( HR , 0.33 ; 95 % CI , 0.13 to 0.84 ) , and decreasing distance traveled to the treating center ( HR , 0.65 ; 95 % CI , 0.44 to 0.98 ) . Patients with zero , one , two , and > or = three risk factors had 5-year competing mortality of 8.9 % ( 95 % CI , 3.0 % to 14.8 % ) , 12.4 % ( 95 % CI , 7.0 % to 17.8 % ) , 22.1 % ( 95 % CI , 14.5 % to 29.7 % ) , and 39.3 % ( 95 % CI , 28.6 % to 50.1 % ) , respectively . CONCLUSION Competing mortality in advanced head and neck cancer is associated with several demographic and health status characteristics . Analyses of risk factors for competing mortality may be useful in outcomes reporting and design ing clinical trials", "PURPOSE To determine the prognostic role of comorbidity in Stage III non-small cell lung cancer ( NSCLC ) treated definitively with radiotherapy alone . METHODS AND MATERIAL S A total of 112 patients with clinical Stage III NSCLC ( American Joint Commission on Cancer 1997 ) enrolled in four Radiation Therapy Oncology Group studies ( 83 - 11 , 84 - 03 , 84 - 07 , and 88 - 08 nonchemotherapy arms ) at a single institution were analyzed retrospectively for overall survival ( OS ) and comorbidity . Of the 112 patients , 105 ( 94 % ) completed their assigned radiotherapy . The median assigned dose was 50.4 Gy to the lymphatics ( range 45 - 50.4 Gy ) and 70.2 Gy to the primary tumor ( range 60 - 79.2 Gy ) . Comorbidity was rated retrospectively using the Cumulative Illness Rating Scale for Geriatrics ( CIRS-G ) and Charlson scales . Karnofsky performance scores ( KPSs ) and weight loss were prospect ively recorded . Because only 8 patients had a KPS of OS of this group was compared with that of the patients with better KPSs ( > 70 ) . RESULTS The median survival was 10.39 months ( range 7.87 - 12.91 ) . The 2- , 3- , and 5-year OS rate was 20.5 % , 12.5 % , and 7.1 % , respectively . On univariate analysis , clinical stage ( IIIA vs. IIIB ) was found to be a statistically significant factor influencing OS ( p = 0.026 ) , and the histologic features , grade , tumor size as measured on CT scans , age , tobacco use , weight loss > or=5 % , and total dose delivered to the primary tumor were not . A KPS of a CIRS-G score of 4 ( extremely severe ; p = 0.0002 ) , and a severity index of > 2 ( p . Multivariate analysis with clinical stage , KPS , and comorbidity ( severity index ) of all patients showed that a KPS 2 were independently associated with inferior OS ; clinical tumor stage was not found to be an independent prognostic factor . CONCLUSION KPS and comorbidity are important independent prognostic factors in Stage III NSCLC . Comorbidity should be included in protocol s study ing advanced stage NSCLC and used for stratification", "OBJECTIVE The aim of the present prospect i ve study was to obtain further insight into health-related quality of life ( HR-QoL ) as a predictor of survival in a selected cohort of patients with oral cancer . STUDY DESIGN A total of 124 patients were treated with surgery or combined therapy . All of the recruited patients completed the European Organization for Research and Treatment of Cancer question naires QLQC30 and H&N35 on 4 occasions . Overall survival was assessed . Univariate and multivariate Cox proportional hazards regression models were conducted . RESULTS High baseline HR-QoL score and high pain symptom score were significantly associated with a better survival ( HR 0.86 and 0.92 respectively ) . Swallowing ( HR 0.94 ) , and speech ( HR 0.92 ) high baseline scores were also significantly associated with a better survival in the adjusted analyses . CONCLUSIONS Patients who reported a better HR-QoL at tumor diagnosis had a better survival than patients with a lower HR-QoL baseline score", "OBJECTIVES We examined the prognostic factors ( clinical , demographic , and health-related quality of life [ HRQoL ] ) of overall survival ( OS ) and progression-free survival ( PFS ) in patients with recurrent/metastatic head and neck cancer ( HNC ) who were treated with pemetrexed plus cisplatin versus cisplatin in a phase III , multinational , r and omized trial . MATERIAL S AND METHODS Five subscales of the Functional Assessment of Cancer Therapy-Head and Neck Cancer ( FACT-H&N ) , modified to score from 0 to 100 , measured HRQoL at baseline and during treatment . Univariate and multivariate Cox proportional hazards models were used on data pooled from both treatment arms to assess the effect of baseline prognostic factors on OS and PFS . RESULTS Of 795 patients r and omized , 704 completed a baseline FACT-H&N and were included in the analysis . Age ( 65 versus ⩾65 ; HR=0.74 , 95 % CI : 0.61 - 0.90 ) , race ( Caucasian versus non-Caucasian ; HR=0.83 , 95 % CI : 0.70 - 0.98 per table ) , Eastern Cooperative Oncology Group performance status ( ECOG PS ; 0/1 versus 2 ; HR=0.44 , 95 % CI : 0.35 - 0.56 ) , prior surgery/radiotherapy in the last 6months ( no versus yes ; HR=0.74 , 95 % CI : 0.61 - 0.90 ) , and primary site of disease ( oral cavity versus other ; HR=1.37 , 95 % CI : 1.15 - 1.63 ) were significantly prognostic of OS in univariate models , as were baseline scores on four FACT-H&N subscales ( physical well-being , emotional well-being , functional well-being , additional concerns-H&N ; HRs=0.82 - 0.94 ; all P⩽0.002 ) . In multivariate models , significant prognostic factors were age ( HR=0.78 ) ; race ( HR=0.76 per table ) ; ECOG PS ( HR=0.56 ) ; prior surgery/radiotherapy ( HR=0.76 ) ; and baseline scores of the FACT-H&N subscales of physical well-being , social/family well-being , and additional concerns-H&N ( HRs=0.89 - 0.94 ; all P⩽0.014 per table ) . CONCLUSIONS The results suggest that baseline HRQoL scores are prognostic indicators of OS in recurrent/metastatic HNC in addition to other known clinical and demographic indicators . HRQoL might be considered as a stratification factor in r and omized clinical trials of recurrent/metastatic HNC", "BACKGROUND Mortality prediction is crucial to select the optimal treatment in elderly cancer patients . Our objective was to identify cancer-related factors and Comprehensive Geriatric Assessment ( CGA ) findings associated with 1-year mortality in elderly in patients and out patients with cancer . METHODS We prospect ively included patients aged ≥70 years who had solid or hematologic malignancies and in whom the CGA was performed by geriatricians in two French teaching hospitals . We identified independent predictors of 1-year mortality after study inclusion , using multivariate Cox models stratified on inpatient/outpatient status . We built three multivariate Cox models , since strong correlations linked activities of daily living ( ADL ) , Eastern Cooperative Oncology Group Performance Status ( ECOG-PS ) , and timed get-up- and -go test ( GUG ) results ; and since physicians ' preferences for these three assessment s vary . A sensitivity analysis was performed using multiple imputation . RESULTS Of the 993 patients ( mean age , 80.2 years ; 51.2 % men ) , 58.2 % were out patients and 46 % had metastatic disease . Colorectal cancer was the most common malignancy ( 21.4 % ) . Mortality rates after 6 and 12 months were 30.1 % and 41.2 % , respectively . In all models , tumor site and metastatic status ( p 80 years ( p higher number of severe comorbidities ( p and malnutrition ( p with death independently from impaired ECOG-PS ( p and GUG ( p ) . The adverse effect of metastatic status differed significantly across tumor sites , being greatest for breast and prostate cancer ( p of 1-year mortality identified in our study may help physicians select the optimal cancer-treatment strategy in elderly patients", "This study was performed to determine preoperative criteria for identifying patients at risk for delirium after major head and neck cancer surgery . The authors prospect ively evaluated 138 consecutive patients undergoing head and neck cancer surgery lasting more than 2 hours at the Arthur G. James Cancer Hospital and Research Institute , Ohio State University , Columbus , from July 1993 through May 1994 . Postoperative delirium developed in 24 of 138 patients ( 17 % ; 95 % confidence interval 11 % to 24 % ) . The strongest univariate predictors of delirium were living alone ( P = .005 ) , the American Society of Anesthesiologists class ( P = .003 ) , and the preoperative white blood cell count ( P postoperative delirium ( i.e. , 9 % , 19 % , and 25 % )", "BACKGROUND The purpose of this study was to evaluate the individual and combined relationship of comorbidity and performance status ( PS ) on head and neck squamous cell carcinoma ( HNSCC ) survival . METHODS Six hundred patients with HNSCC were prospect ively recruited . Comorbidity and PS were measured using the Charlson Comorbidity Index ( CCI ) and the Eastern Cooperative Oncology Group ( ECOG ) Scale . Outcomes were overall survival ( OS ) and cancer-specific survival ( CSS ) . RESULTS A total of 48.3 % of the patients had at least 1 comorbidity , and 42.3 % had impaired PS at baseline . There was no correlation between CCI and ECOG ( Spearman 's ρ = 0.033 ; p = .42 ) . In multivariate analysis , CCI score was significantly associated with OS ( p = .01 ) . ECOG was not associated with OS , but seems to act as an effect modifier in the association between comorbidity and OS . CCI and ECOG were not associated with CSS . CONCLUSION CCI and ECOG scores both provide prognostic information in predicting OS in HNSCC , but a significant association with CSS was not observed", "BACKGROUND Head and neck cancer and its treatment can have considerable impact on health-related quality of life ( HRQOL ) . The present study investigated whether social support , assessed before treatment , predicted HRQOL outcomes up to 12 months later in head and neck cancer survivors . METHODS Using a prospect i ve longitudinal design , patients ( n = 364 ) were assessed on several clinical and psychosocial characteristics at diagnosis and then at 3- and 12-month follow-up appointments . HRQOL was assessed with the Short Form Health Survey ( SF-36 ) and the Head and Neck Cancer Inventory ( HNCI ) . RESULTS Hierarchical multiple regression analyses demonstrated that greater perceived support present at diagnosis significantly predicted more favorable global and head and neck cancer-specific HRQOL at 3- and 12-month follow-up . CONCLUSION Results suggest that adequate social support at diagnosis can have a significant , positive impact on HRQOL in head and neck cancer survivors . Thus , it may be useful to evaluate support re sources at diagnosis in order to identify individuals at risk for poor HRQOL outcomes" ]	411889a2-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Exercise programmes are a relatively inexpensive , low-risk option compared with other , more invasive therapies for treatment of leg pain on walking ( intermittent claudication ( IC ) ) . This is the fourth up date of a review first published in 1998 . OBJECTIVES Our goal was to determine whether an exercise programme was effective in alleviating symptoms and increasing walking treadmill distances and walking times in people with intermittent claudication . Secondary objectives were to determine whether exercise was effective in preventing deterioration of underlying disease , reducing cardiovascular events , and improving quality of life . SEARCH METHODS For this up date , the Cochrane Vascular Information Specialist search ed the Specialised Register ( last search ed 15 November 2016 ) and the Cochrane Central Register of Controlled Trials ( CENTRAL ; 2016 , Issue 10 ) via the Cochrane Register of Studies Online , along with trials registries . SELECTION CRITERIA R and omised controlled trials of an exercise regimen versus control or versus medical therapy for people with IC due to peripheral arterial disease ( PAD ) . We included any exercise programme or regimen used for treatment of IC , such as walking , skipping , and running . Inclusion of trials was not affected by duration , frequency , or intensity of the exercise programme . Outcome measures collected included treadmill walking distance ( time to onset of pain or pain-free walking distance and maximum walking time or maximum walking distance ) , ankle brachial index ( ABI ) , quality of life , morbidity , or amputation ; if none of these was reported , we did not include the trial in this review . DATA COLLECTION AND ANALYSIS For this up date ( 2017 ) , RAL and AH selected trials and extracted data independently . We assessed study quality by using the Cochrane ' Risk of bias ' tool . We analysed continuous data by determining mean differences ( MDs ) and 95 % confidence intervals ( CIs ) , and dichotomous data by determining risk ratios ( RRs ) and 95 % CIs . We pooled data using a fixed-effect model unless we identified significant heterogeneity , in which case we used a r and om-effects model . We used the GRADE approach to assess the overall quality of evidence supporting the outcomes assessed in this review . MAIN RESULTS We included two new studies in this up date and identified additional publications for previously included studies , bringing the total number of studies meeting the inclusion criteria to 32 , and involving a total of 1835 participants with stable leg pain . The follow-up period ranged from two weeks to two years . Types of exercise varied from strength training to polestriding and upper or lower limb exercises ; supervised sessions were generally held at least twice a week . Most trials used a treadmill walking test for one of the primary outcome measures . The method ological quality of included trials was moderate , mainly owing to absence of relevant information . Most trials were small and included 20 to 49 participants . Twenty-seven trials compared exercise versus usual care or placebo , and the five remaining trials compared exercise versus medication ( pentoxifylline , iloprost , antiplatelet agents , and vitamin E ) or pneumatic calf compression ; we generally excluded people with various medical conditions or other pre-existing limitations to their exercise capacity . Meta- analysis from nine studies with 391 participants showed overall improvement in pain-free walking distance in the exercise group compared with the no exercise group ( MD 82.11 m , 95 % CI 71.73 to 92.48 , P exercise in improved maximum walking distance ( MD 120.36 m , 95 % CI 50.79 to 189.92 , P 10 studies with 500 participants . Improvements were seen for up to two years . Exercise did not improve the ABI ( MD 0.04 , 95 % CI 0.00 to 0.08 , 13 trials , 570 participants , moderate- quality evidence ) . Limited data were available for the outcomes of mortality and amputation ; trials provided no evidence of an effect of exercise , when compared with placebo or usual care , on mortality ( RR 0.92 , 95 % CI 0.39 to 2.17 , 5 trials , 540 participants , moderate- quality evidence ) or amputation ( RR 0.20 , 95 % CI 0.01 to 4.15 , 1 trial , 177 participants , low- quality evidence ) . Research ers measured quality of life using Short Form (SF)-36 at three and six months . At three months , the domains ' physical function ' , ' vitality ' , and ' role physical ' improved with exercise ; however this was a limited finding , as it was reported by only two trials . At six months , meta- analysis showed improvement in ' physical summary score ' ( MD 2.15 , 95 % CI 1.26 to 3.04 , P = 0.02 , 5 trials , 429 participants , moderate- quality evidence ) and in ' mental summary score ' ( MD 3.76 , 95 % CI 2.70 to 4.82 , P exercise . Two trials reported the remaining domains of the SF-36 . Data showed improvements secondary to exercise in ' physical function ' and ' general health ' . The other domains - ' role physical ' , ' bodily pain ' , ' vitality ' , ' social ' , ' role emotional ' , and ' mental health ' - did not show improvement at six months . Evidence was generally limited in trials comparing exercise versus antiplatelet therapy , pentoxifylline , iloprost , vitamin E , and pneumatic foot and calf compression owing to small numbers of trials and participants . Review authors used GRADE to assess the evidence presented in this review and determined that quality was moderate to high . Although results showed significant heterogeneity between trials , population s and outcomes were comparable overall , with findings relevant to the claudicant population . Results were pooled for large sample sizes - over 300 participants for most outcomes - using reproducible methods . AUTHORS ' CONCLUSIONS High- quality evidence shows that exercise programmes provided important benefit compared with placebo or usual care in improving both pain-free and maximum walking distance in people with leg pain from IC who were considered to be fit for exercise intervention . Exercise did not improve ABI , and we found no evidence of an effect of exercise on amputation or mortality . Exercise may improve quality of life when compared with placebo or usual care . As time has progressed , the trials undertaken have begun to include exercise versus exercise or other modalities ; therefore we can include fewer of the new trials in this up date	[ "OBJECTIVE : To assess the acute metabolic and cardiovascular responses to walking exercise at an intensity corresponding to the heart rate of claudication pain onset and to investigate the effects of a 12-week walking training program at this intensity on walking capacity . METHODS : Twenty-nine patients with intermittent claudication were r and omly allocated to the walking training ( n = 17 ) or control ( CO , n = 12 ) group . The walking training group performed an acute exercise session comprising 15 × 2-min bouts of walking at the heart rate of claudication pain onset , with 2-min interpolated rest intervals . The claudication symptoms and cardiovascular and metabolic responses were evaluated . Walking training was then performed at the same intensity twice each week for 12 weeks , while the control group engaged in twice weekly stretching classes . The claudication onset distance and total walking distance were evaluated before and after the interventions . Brazilian Registry Clinical Trials : RBR-7M3D8W . RESULTS : During the acute exercise session , the heart rate was maintained within tight limits . The exercise intensity was above the anaerobic threshold and > 80 % of the heart rate peak and VO2peak . After the exercise training period , the walking exercise group ( n = 13 ) showed increased claudication onset distance ( 309±153 vs. 413±201 m ) and total walking distance ( 784±182 vs. 1,100±236 m ) compared to the control group ( n = 12 ) ( p CONCLUSION : Walking exercise prescribed at the heart rate of claudication pain onset enables patients with intermittent claudication to exercise with tolerable levels of pain and improves walking performance", "This study examined whether a training intervention likely to elicit adaptations in the leg could result in reduced leg pain and increased whole body physical capacity . Twenty-seven peripheral arterial disease ( PAD ) patients were r and omized to either an individual leg plantar flexion training group ( TG ) training 4 × 4 min intervals at 80 % of maximal work rate three times per week for 8 weeks or a control group . The TG significantly increased plantar flexion peak oxygen uptake and power output by 23.5 and 43.9 % , respectively . Treadmill peak oxygen uptake ( VO2peak ) significantly increased 12.3 % in the TG and was associated with a significant increased time to exhaustion of 20.0 % when treadmill walking . Eleven of 14 patients no longer reported leg pain limitations at VO2peak . No differences in cardiac output measured at VO2peak , or walking economy were observed . Plantar flexion training was effective in increasing VO2peak and walking performance , and may be a useful strategy in treatment of PAD", "In a vascular rehabilitation program , 28 % of our frail elderly patients are unable to be tested with traditional progressive exercise protocol s at program entry due to the high ( 2.0 miles/h or 3.2 km/h ) initial treadmill speeds . The purpose of this investigation was to compare a new progressive treadmill protocol which has a reduced initial speed ( 1.0 mile/h or 1.6 km/h ) to an established protocol performed at 2.0 miles/h ( 3.2 km/h ) to determine the comparability and reproducibility of the new protocol . Eleven patients with arterial claudication performed three symptom-limited exercise tests in r and om order . Two tests used the new protocol while the remaining trial used the established protocol . Claudication pain was measured using a 5-point scale . Oxygen consumption , heart rate , minute ventilation , respiratory exchange ratio and blood pressure at peak exercise were similar among the three trials . There were strong intra-class correlations for peak oxygen consumption ( r = 0.97 ) , onset of claudication ( r = 0.96 ) and maximum walking time ( r = 0.98 ) between the two trials using the new protocol . There was also a significant correlation between the new protocol and the established protocol for peak oxygen consumption ( r = 0.90 ) and maximum walking time ( r = 0.89 ) . The new progressive treadmill protocol represents a valid , reliable protocol for patients with arterial claudication . This protocol may be useful for testing patients with a low functional capacity so that clinical ly appropriate exercise prescriptions can be established and the efficacy of treatments can be determined", "BACKGROUND This prospect i ve , r and omized controlled clinical trial determined whether an optimal exercise program length exists to efficaciously change claudication onset time ( COT ) and peak walking time ( PWT ) in patients with peripheral artery disease and claudication . METHODS The study r and omized 142 patients to supervised exercise ( n = 106 ) or a usual care control group ( n = 36 ) , with 80 completing the exercise program and 27 completing the control intervention . The exercise program consisted of intermittent walking to nearly maximal claudication pain 3 days per week . COT and PWT were the primary outcomes obtained from a treadmill exercise test at baseline and bimonthly during the study . RESULTS After exercise , changes in COT ( P PWT ( P exercise program , COT and PWT increased from baseline to month 2 ( P .05 ) . When changes were expressed per mile walked during the first 2 months , middle 2 months , and final 2 months of exercise , COT and PWT only increased during the first 2 months ( P gains in COT and PWT occur rapidly within the first 2 months of exercise rehabilitation and are maintained with further training . The clinical significance is that a relatively short 2-month exercise program may be preferred to a longer program to treat claudication because adherence is higher , costs associated with personnel and use of facilities are lower per patient , and more patients can be trained for a given amount of personnel time and re source utilization", "1 . The activities of phosphofructokinase ( PFK ) , citrate synthetase ( CS ) , lactate dehydrogenase ( LDH ) , 3-hydroxyacyl-CoA dehydrogenase ( ACDH ) and cytochrome-c oxidase(Cyt-ox ) in the calf muscle tissue were compared in subjects with intermittent claudication ( n = 38 ) and controls ( n = 20 ) . The activities of CS , ACDH and Cyt-ox were increased and the activity of Cytox was positively correlated to the maximal walking distance ( MWD ) in the patients . 2 . Thirty-three patients with intermittent claudication were r and omized to three treatment groups : ( 1 ) operative surgery , ( 2 ) operative surgery supplemented with physical training and ( 3 ) physical training alone . Before and after 6 - 12 months of treatment , symptom-free walking distance ( SFWD ) , MWD , ankle-brachial blood pressure quotient ( ankle index ) , maximal plethysmographic calf blood flow ( MPBF ) and the activities of PFK , CS , LDH , ACDH and Cyt-ox were measured . 3 . SFWD and MWD increased in all three groups . Ankle index and MPBF increased in groups 1 and 2 , but were unchanged in group 3 . The activities of Cyt-ox and CS decreased with operation , but the activity of Cyt-ox was further augmented with training in group 3 . Overall , the change in ankle index explained 80 - 90 % of the variability in walking performance . In a separate analysis , the increased activity of Cyt-ox in group 3 was positively correlated to , and explained 31 % of the variability in , the improvement in SFWD . 4 . These findings indicate that both physical activity and a reduced calf blood flow are necessary conditions for the enzymatic adaptation to take place . A causal relationship between metabolic adaptation in the muscle tissue and walking performance is suggested . ( ABSTRACT TRUNCATED AT 250 WORDS", "BACKGROUND In patients with intermittent claudication , a supervised walking exercise program increases peak exercise performance and community-based functional status . Patients with peripheral arterial disease also have muscle weakness in the affected extremity that may contribute to the walking impairment . However , the potential benefits of training modalities other than walking exercise , such as strength training , have not been critically evaluated in this patient population . The present study tested the hypothesis that a strength training program would be as effective as treadmill walking exercise and that combinations of strengthening and walking exercise would be more effective than either alone in improving exercise performance . METHODS AND RESULTS Twenty-nine patients with disabling claudication were r and omized to 12 weeks of supervised walking exercise on a treadmill ( 3 h/wk at a work intensity sufficient to produce claudication ) , strength training ( 3 h/wk of resistive training of five muscle groups of each leg ) , or a nonexercising control group . Grade d treadmill testing was performed to maximally tolerated claudication pain to define changes in peak exercise performance . After 12 weeks , patients in the treadmill training program had a 74 + /- 58 % increase in peak walking time as well as improvements in peak oxygen consumption ( VO2 ) and the onset of claudication pain . Patients in the strength-trained group had a 36 + /- 48 % increase in peak walking time but no change in peak VO2 or claudication onset time . Control subjects had no changes in any of these measures over the 12-week period . After the first 12 weeks , patients in the initial walking exercise group continued for 12 more weeks of supervised treadmill training . This result ed in an additional 49 + /- 53 % increase in peak walking time ( total of 128 + /- 99 % increase over the 24 weeks ) . After the initial 12 weeks , patients in the strength-trained group began 12 weeks of supervised treadmill training , and patients in the control group participated in a 12-week combined program of strengthening and treadmill walking exercise . The combined strength and treadmill training program and treadmill training after 12 weeks of strength training result ed in increases in peak exercise performance similar to those observed with 12 weeks of treadmill training alone . CONCLUSIONS A supervised treadmill walking exercise program is an effective means to improve exercise performance in patients with intermittent claudication , with continued improvement over 24 weeks of training . In contrast , 12 weeks of strength training was less effective than 12 weeks of supervised treadmill walking exercise . Finally , strength training , whether sequential or concomitant , did not augment the response to a walking exercise program", "Background Few medical therapies improve lower extremity functioning in people with lower extremity peripheral artery disease ( PAD ) . Among people with PAD , we studied whether a group-mediated cognitive behavioral intervention promoting home-based unsupervised exercise prevented mobility loss and improved functional performance compared to control . Methods and Results One hundred ninety-four PAD participants were r and omized . During months 1 to 6 , the intervention group met weekly with other PAD participants and a facilitator . Group support and self-regulatory skills were used to help participants adhere to walking exercise . Ninety-percent of exercise was conducted at or near home . The control group attended weekly lectures . During months 6 to 12 , each group received telephone contact only . Primary outcomes have been reported . Here we compare changes in exploratory outcomes of mobility loss ( the inability to climb a flight of stairs or walk one-quarter mile without assistance ) , walking velocity , and the Short Physical Performance Battery . Compared to controls , fewer participants r and omized to the intervention experienced mobility loss at 6-month follow-up : 6.3 % versus 26.5 % , P=0.002 , odds ratio=0.19 ( 95 % CI=0.06 to 0.58 ) and at 12-month follow-up : 5.2 % versus 18.5 % , P=0.029 , odds ratio=0.24 ( 95 % CI=0.06 to 0.97 ) . The intervention improved fast-paced 4-m walking velocity at 6-month follow-up ( P=0.005 ) and the Short Physical Performance Battery at 12-month follow-up ( P=0.027 ) , compared to controls . Conclusions In exploratory analyses , a group-mediated cognitive behavioral intervention promoting unsupervised walking exercise prevented mobility loss and improved functioning at 6- and 12-month follow-up in PAD patients . Clinical Trial Registration URL : http:// clinical trials.gov . Unique identifier : NCT00693940", "PURPOSE A pilot study was conducted to test the feasibility of supervised treadmill exercise training to improve functioning in study participants with peripheral arterial disease who did not have classical symptoms of intermittent claudication . METHODS For this study , 32 men and women with peripheral arterial disease but no symptoms of claudication were r and omized to exercise training or usual care . The intervention was a 12-week supervised treadmill walking program . Outcomes included 6-minute walk distance , maximum treadmill walking distance , and 4-meter walking velocity . Participant-reported community walking ability was measured with the Walking Impairment Question naire ( WIQ ) . Inflammatory blood factor levels also were measured . RESULTS Altogether , 25 participants who completed follow-up testing were included in intention-to-treat analyses . Of 24 participants ( 58 % ) r and omized to exercise , 14 completed the entire exercise training program . The participants r and omized to the intervention showed greater improvement in their WIQ walking speed score than the control subjects ( P = .05 ) . The participants r and omized to the intervention showed improvements in their 6-minute walk distance ( 1134 + /- 347 vs 1266 + /- 295 feet ; P = .03 ) , maximal treadmill walking distance ( 389 + /- 248 vs 585 + /- 293 feet ; P WIQ distance score ( 52.3 + /- 29.1 vs 63.1 + /- 25.1 ; P = .002 ) , and WIQ speed score ( 48.7 + /- 26.8 vs 59.7 + /- 22.7 ; P = .008 ) . The participants r and omized to the control condition showed improvements in maximal treadmill walking distance ( 362 + /- 180 vs 513 + /- 237 feet ; P = .014 ) . There were no significant changes in the inflammatory blood factors after exercise . CONCLUSIONS This pilot study demonstrated that a supervised treadmill walking program may be feasible and may improve functioning for individuals with peripheral arterial disease who do not have classical symptoms of intermittent claudication . Further study is needed with a larger sample to identify optimal exercise methods that improve lower extremity functioning in men and women with peripheral arterial disease who do not have intermittent claudication", "The extent and clinical significance of stem and progenitor cell ( SPC ) increases in response to lower-extremity ischemia in people with peripheral artery disease ( PAD ) are unclear . We compared changes in SPC levels immediately following a treadmill exercise test between individuals with and without PAD . Among participants with PAD , we determined whether more severe PAD was associated with greater increases in SPCs following treadmill exercise-induced lower-extremity ischemia . We measured SPC levels in 25 participants with PAD and 20 without PAD before and immediately after a treadmill exercise test . Participants with PAD , compared to participants without PAD , had greater increases in CD34+CD45dim ( + 0.08±0.03 vs −0.06±0.04 , p=0.008 ) , CD34+CD45dimCD133 + ( + 0.08±0.05 vs −0.08±0.04 , p=0.014 ) , CD34+CD45dimCD31 + ( + 0.10±0.03 vs −0.07±0.04 , p=0.002 ) , and CD34+CD45dimALDH+ SPCs ( + 0.18±0.07 vs −0.05±0.08 , p=0.054 ) measured as a percentage of all white blood cells . Among participants with PAD , those with any increases in the percent of SPCs immediately after the treadmill exercise test compared to those with no change or a decrease in SPCs had lower baseline ankle – brachial index values ( 0.65±0.17 vs 0.90±0.19 , p=0.004 ) and shorter treadmill times to onset of ischemic leg symptoms ( 2.17±1.54 vs 5.25±3.72 minutes , p=0.012 ) . In conclusion , treadmill exercise-induced lower-extremity ischemia is associated with acute increases in circulating SPCs among people with PAD . More severe PAD is associated with a higher prevalence of SPC increases in response to lower-extremity ischemia . Further prospect i ve study is needed to establish the prognostic significance of ischemia-related increases in SPCs among patients with PAD", "Intermittent claudication is the primary symptom of peripheral arterial disease , affecting between 1 and 3 million Americans . Symptomatic improvement can be achieved by endovascular revascularization , but such procedures are invasive , expensive , and may be associated with procedural adverse events . Medical treatment options , including claudication medications and supervised exercise training , are also known to be effective , albeit also with associated limitations . The CLEVER ( Claudication : Exercise Vs . Endoluminal Revascularization ) study , funded by the Heart , Lung , and Blood Institute of the National Institutes of Health , is a prospect i ve , multicenter , r and omized , controlled clinical trial evaluating the relative efficacy , safety , and health economic impact of four treatment strategies for people with aortoiliac peripheral arterial disease and claudication . The treatment arms are : ( 1 ) optimal medical care ( claudication pharmacotherapy ) ; ( 2 ) primary stent placement ; ( 3 ) supervised exercise rehabilitation ; and ( 4 ) combined stenting with supervised exercise rehabilitation . The CLEVER study is a 5-year r and omized , controlled clinical trial to be conducted at approximately 25 centers in the United States that will monitor 252 patients and their responses to treatment during an 18-month follow-up period . The primary end point is change in maximum walking duration on a grade d treadmill test . Secondary end points include the change at 18 months in maximum walking duration from baseline , comparisons of free-living daily activity levels assessed by pedometer , health-related quality of life , and cost-effectiveness . Other analyses include the effect of these treatment strategies on anthropomorphic and physiologic variables , including body mass index , waist circumference , blood pressure , pulse pressure , and resting pulse as well as biochemical markers of cardiovascular health , including fasting lipids , fibrinogen , C-reactive protein , and hemoglobin A 1c values", "Patients with atherosclerotic peripheral arterial disease ( PAD ) of the lower extremities have impaired walking ability due to exercise-induced muscle ischemia and the result ant pain of intermittent claudication . To evaluate the benefit of exercise training as a treatment for patients with PAD , as well as possible mechanisms associated with improvement , we r and omly assigned 19 men with disabling claudication to treated and control groups . Treatment consisted of supervised treadmill walking ( 1 hr/day , 3 days/wk , for 12 weeks ) with progressive increases in speed and grade as tolerated . Grade d treadmill testing was performed to maximal toleration of claudication pain on entry and after 12 weeks of training to define changes in peak exercise performance . After 12 weeks , treated subjects had increased their peak walking time 123 % , peak oxygen consumption 30 % , and pain-free walking time 165 % ( all p less than 0.05 ) . Control subjects had no change in peak oxygen consumption , but after 12 weeks , peak walking time increased 20 % ( p less than 0.05 ) . In treated subjects , maximal calf blood flow ( measured by a plethysmograph ) increased 38 + /- 45 % ( p less than 0.05 ) , but the change in flow was not correlated to the increase in peak walking time . Elevated plasma concentrations of acylcarnitines have been associated with the functional impairment of PAD and may reflect the metabolic state of ischemic skeletal muscle . In treated subjects , a 26 % decrease in resting plasma short-chain acylcarnitine concentration was correlated with improvement in peak walking time ( r = -0.78 , p less than 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS", "OBJECTIVE Exercise advice is the main treatment for symptom relief in the UK for patients with mild to moderate Intermittent Claudication ( IC ) . Would a weekly exercise and motivation class for 6 months offer adjuvant benefit over written and verbal exercise advice alone ? PATIENTS AND METHODS Fifty-nine patients attending a regional vascular centre for whom IC was the main factor affecting mobility were r and omised to either exercise advice alone ( n=30 ) or exercise advice with a once a week 45 min supervised exercise/motivation class ( n=29 ) . The mean age was 68 years . Baseline and 6-month assessment included a Quality of Life Question naire -- the Short-Form-36 , the Charing Cross Symptom Specific Claudication Question naire ( CCCQ ) and treadmill walking distance ( 3.5 km/h 12 % ) . RESULTS At 6-month follow-up the supervised exercise group had improved their treadmill walking by 129 % compared to 69 % in the advice alone group ( p=0.001 ) . This significant improvement was maintained at the subsequent 9 and 12-month follow-up assessment s. By the 9-month stage the advice only group CCCQ score had improved 16 % from baseline , while the supervised exercise group had a significantly better 43 % improvement in base line score ( p Self reported frequency of walks was higher in the exercise class group being significant for improvement in CCCQ score . CONCLUSION A weekly , supervised exercise and motivation class for a 6-month period provides a significant improvement in patients ' symptoms , quality of life , and distance walked compared with advice alone and this improvement continues after attendance at class has ceased", "IMPORTANCE Clinical practice guidelines state there is insufficient evidence to support advising patients with peripheral artery disease ( PAD ) to participate in a home-based walking exercise program . OBJECTIVE To determine whether a home-based walking exercise program that uses a group-mediated cognitive behavioral intervention , incorporating both group support and self-regulatory skills , can improve functional performance compared with a health education control group in patients with PAD with and without intermittent claudication . DESIGN , SETTING , AND PATIENTS R and omized controlled clinical trial of 194 patients with PAD , including 72.2 % without classic symptoms of intermittent claudication , performed in Chicago , Illinois between July 22 , 2008 , and December 14 , 2012 . INTERVENTIONS Participants were r and omized to 1 of 2 parallel groups : a home-based group-mediated cognitive behavioral walking intervention or an attention control condition . MAIN OUTCOMES AND MEASURES The primary outcome was 6-month change in 6-minute walk performance . Secondary outcomes included 6-month change in treadmill walking , physical activity , the Walking Impairment Question naire ( WIQ ) , and Physical and Mental Health Composite Scores from the 12-item Short-Form Health Survey . RESULTS Participants r and omized to the intervention group significantly increased their 6-minute walk distance ( [ reported in meters ] 357.4 to 399.8 vs 353.3 to 342.2 for those in the control group ; mean difference , 53.5 [ 95 % CI , 33.2 to 73.8 ] ; P .001 ) , maximal treadmill walking time ( intervention , 7.91 to 9.44 minutes vs control , 7.56 to 8.09 ; mean difference , 1.01 minutes [ 95 % CI , 0.07 to 1.95 ] ; P = .04 ) , accelerometer-measured physical activity over 7 days ( intervention , 778.0 to 866.1 vs control , 671.6 to 645.0 ; mean difference , 114.7 activity units [ 95 % CI , 12.82 to 216.5 ] ; P = .03 ) , WIQ distance score ( intervention , 35.3 to 47.4 vs control , 33.3 to 34.4 ; mean difference , 11.1 [ 95 % CI , 3.9 to 18.1 ] ; P = .003 ) , and WIQ speed score ( intervention , 36.1 to 47.7 vs control , 35.3 - 36.6 ; mean difference , 10.4 [ 95 % CI , 3.4 to 17.4 ] ; P = .004 ) . CONCLUSION AND RELEVANCE A home-based walking exercise program significantly improved walking endurance , physical activity , and patient-perceived walking endurance and speed in PAD participants with and without classic claudication symptoms . These findings have implication s for the large number of patients with PAD who are unable or unwilling to participate in supervised exercise programs . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00693940", "The aim of this study was to develop and pilot a group education programme for promoting walking in people with intermittent claudication . Patient focus groups ( n=24 ) and literature review s were conducted to inform the development of the education programme , which involves a three-hour group-based education workshop and follow-up telephone support . A pilot study was subsequently conducted in which 23 new patients ( Rutherford category 1–3 ) were r and omly assigned to usual care ( control ) or usual care plus the education programme . Outcomes were assessed at baseline and six weeks including daily steps ( tri-axial accelerometer ) , walking capacity ( six-minute walk test and Gardner treadmill test ) , and quality of life ( Intermittent Claudication Question naire [ ICQ ] ) . Exit interviews were conducted to assess the acceptability and usefulness of the programme . Compared with controls , the intervention group had superior walking capacity and quality of life at six weeks . Mean differences in six-minute walk distance , treadmill maximum walking distance and ICQ score were 44.9 m ( 95 % confidence interval [ CI ] , 6.9 to 82.9 ) , 173 m ( 95 % CI , 23 to 322 ) , and −10.6 ( 95 % CI , −18.9 to −2.3 ) , respectively . The daily step count did not differ between groups . The exit interviews indicated that participants valued attending the programme , that it gave them a greater underst and ing of their condition , and that they had been walking more for exercise since attending . The results suggest that the education programme is feasible , acceptable , and potentially useful for improving walking capacity and quality of life . A fully-powered trial exploring clinical and cost effectiveness is needed . TRIAL REGISTRATION NUMBER : IS RCT N06733130 ( http://www.controlled-trials.com )", "BACKGROUND To compare angioplasty ( PTA ) , supervised exercise ( SEP ) and PTA + SEP in the treatment of intermittent claudication ( IC ) due to femoropopliteal disease . METHODS Over a 6-year period , 178 patients ( 108 men ; median age , 70 years ) with femoropopliteal lesions suitable for angioplasty were r and omized to PTA , SEP , or PTA + SEP . Patients were assessed prior to and at 1 and 3 months post treatment . ISCVS outcome criteria ( ankle pressures , treadmill walking distances ) and quality of life ( QoL ) question naires ( SF-36 and VascuQoL ) were analyzed . RESULTS All groups were well matched at baseline . Twenty-one patients withdrew . Results are as follows : Intragroup analysis : All groups demonstrated significant clinical and QoL improvements ( Friedman test , p SEP ( 60 patients , 8 withdrew)-62.7 % of patients ( n = 32 ) improved following treatment [ 20 mild , 9 moderate , 3 marked ] , 27.4 % ( n = 14 ) demonstrated no improvement , and 9.8 % ( n = 5 ) deteriorated . PTA ( 60 patients , 3 withdrew)-66.6 % patients ( n = 38 ) improved following treatment [ 19 mild , 10 moderate , 9 marked ] , 22.8 % ( n = 13 ) demonstrated no improvement , and 10.5 % ( n = 6 ) deteriorated . PTA + SEP ( 58 patients , 10 withdrew)-81.6 % of patients ( n = 40 ) improved following treatment [ 10 mild , 17 moderate , 3 marked ] , 14.2 % ( n = 7 ) demonstrated no improvement , and 4.0 % ( n = 2 ) deteriorated . Intergroup analysis : PTA + SEP produce a much greater improvement in clinical outcome measures than PTA or SEP alone , but there was no significant QoL advantage ( Kruskal-Wallis test , p > 0.05 ) . CONCLUSION SEP should be the primary treatment for the patients with claudication and PTA should be supplemented by an SEP ", "Background PAD is a disabling , chronic condition of the lower extremities that affects approximately 8 million people in the United States . The purpose of this study was to determine whether an innovative home-based walking exercise program for patients with peripheral artery disease ( PAD ) improves self-efficacy for walking , desire for physical competence , satisfaction for physical functioning , social functioning , and acceptance of PAD related pain and discomfort . Methods The design was a 6-month r and omized controlled clinical trial of 194 patients with PAD . Participants were r and omized to 1 of 2 parallel groups : a home-based group-mediated cognitive behavioral walking intervention or an attention control condition . Results Of the 194 participants r and omized , 178 completed the baseline and 6-month follow-up visit . The mean age was 70.66 ( ±9.44 ) and was equally represented by men and women . Close to half of the cohort was African American . Following 6-months of treatment , the intervention group experienced greater improvement on self-efficacy ( p = .0008 ) , satisfaction with functioning ( p = .0003 ) , pain acceptance ( p = .0002 ) , and social functioning ( p = .0008 ) than the control group ; the effects were consistent across a number of potential moderating variables . Change in these outcomes was essentially independent of change in 6-minute walk performance . Trial registration [ Clinical Trials.gov Identifier : NCT00693940", "Percutaneous transluminal angioplasty ( PTA ) is a commonly performed procedure for the treatment of intermittent claudication despite the lack of controlled studies . The aim of this study was to compare PTA with supervised exercise therapy for patients with arterial occlusive disease judged suitable for PTA at angiography . Patients were assessed before treatment commenced and at three monthly intervals afterwards . Assessment included measurement of resting ankle brachial pressure indices ( ABPI ) , and claudicating and maximum walking distances on a treadmill up a 10 degrees incline . Twenty patients were r and omised to receive PTA and 16 exercise . The groups were similar in age , sex , smoking habits and arteriographic pattern of disease . In the PTA group two patients had angioplasties that were technically unsuccessful and two other patients subsequently required surgery . One patient in the exercise group subsequently had a PTA . After PTA , mean ABPI were significantly improved at 3 , 6 and 9 months ( P less than 0.01 ) without a corresponding significant increase in mean maximum walking distances . However in the exercise group despite no increase in mean ABPI , mean maximum walking distances increased progressively , with significant increases at 6 , 9 and 12 months ( P less than 0.01 )", "BACKGROUND Supervised treadmill-walking exercise programs have been proven to be a highly effective in improving walking distance in peripheral arterial disease ( PAD ) patients with lifestyle-limiting claudication . Limited information is available on the contributions of central cardiorespiratory functions for improving these patients ' walking capacity with exercise training . METHODS This study r and omized 28 participants ( 21 men ; age , 65.6 years ; 92.7 % smoking history , 36.6 % with diabetes ) with lifestyle-limiting PAD-related claudication to 3 hours/week of supervised exercise training for 12 weeks , using arm-ergometry ( n = 10 ) or treadmill-walking ( n = 10 ) vs a usual-care control group ( n = 8) . Cardiorespiratory function measurements were assessed before and after training at a submaximal workload and at the onset of claudication ( pain-free walking distance [ PFWD ] ) and at maximal walking distance [ ( MWD ] ) . Changes in these functions from baseline were analyzed among the groups with analysis of covariance . Associations between variables were determined by Pearson 's partial correlations . RESULTS The mean baseline demographic , medical , and exercise variables were similar among the groups . There were similar significant differences in the submaximal double product ( heart rate × systolic blood pressure ) and at MWD , ventilatory threshold , ventilatory oxygen uptake ( VO(2 ) ) at onset of claudication , and VO(2 ) peak in response to training in both exercise groups vs the control group . Statistically significant , moderate correlations ( r = 0.60 - 0.68 ) were found between changes in all cardiorespiratory variables and changes in PFWD or MWD . CONCLUSION Improvements in cardiorespiratory function after arm-ergometry or treadmill-training were significantly associated with improvements in both PFWD and MWD , providing supporting evidence of systemic contributions to exercise training-related improvements in walking capacity seen in patients with claudication", "OBJECTIVE The efficacy of polestriding exercise ( walking with modified ski poles with a movement pattern similar to cross-country skiing ) to increase exercise tolerance of persons with intermittent claudication pain caused by peripheral arterial disease was tested in this 24-week prospect i ve r and omized clinical trial . METHODS The study was conducted in a Department of Veterans Affairs Hospital with 52 individuals who gave written informed consent and were r and omized into either a polestriding exercise ( n = 27 ; age , 65.5 + /- 7.0 years ; ankle brachial index , 0.64 + /- 0.25 ) or nonexercise control ( n = 25 ; age , 68.6 + /- 8.9 years ; ankle brachial index , 0.69 + /- 0.14 ) group ( P > .05 for all comparisons ) . The polestriding exercise program consisted of supervised training three times per week for 4 weeks , two times per week for 8 weeks , one time per week for 4 weeks , biweekly for 4 weeks and unsupervised training for 4 weeks . Starting in week 5 , subjects took their poles home with instructions to repeat the most recent supervised training walk at an appropriate and convenient location near their residence . This was referred to as unsupervised but directed exercise . Subjects were provided with a personal log book for documenting unsupervised exercise sessions . With both supervised and unsupervised exercise , subjects were expected to complete a total of four 30-minute to 45-minute polestriding exercise sessions per week . The main outcome measures were exercise duration on symptom-limited incremental treadmill test , Walking Impairment Question naire , rating of perceived leg pain at baseline , 4 , 8 , 12 , 16 , and 24 weeks , and constant work-rate treadmill exercise tests at baseline and at 4 , 12 , and 24 weeks . RESULTS Polestriding significantly ( P exercise tolerance on the constant work-rate and incremental treadmill tests . Ratings of perceived claudication pain were significantly less after the polestriding training program . Subject perceived distance and walking speed scores on the Walking Impairment Question naire improved in the polestriding trained group only ( P polestriding training significantly improves quantitative and qualitative measures of the exercise tolerance of persons limited by intermittent claudication pain", "OBJECTIVE To compare associations of physical activity during daily life with treadmill walking performance and corridor-based functional performance measures in persons with lower extremity peripheral arterial disease ( PAD ) . STUDY DESIGN Cross-sectional . SUBJECTS One hundred fifty-six men and women with PAD who completed baseline measurements and were r and omized into the study to improve leg circulation ( SILC ) exercise clinical trial . MAIN OUTCOME MEASURES Participants completed a Gardner-Skinner treadmill protocol . Corridor-based functional performance measures were the 6-minute walk , walking velocity over four meters at usual and fastest pace , and the short physical performance battery ( SPPB ) ( 0 - 12 scale , 12 = best ) . Physical activity during daily life was measured continuously over 7 days with a Caltrac ( Muscle Dynamics Fitness Network , Inc , Torrence , Calif ) accelerometer . RESULTS Adjusting for age , gender , and race , higher levels of physical activity during daily life were associated with greater distance achieved in the 6-minute walk ( P trend = .001 ) , faster fast-paced four-meter walking velocity ( P trend usual-paced four-meter walking speed ( P trend = .027 ) and a higher SPPB ( P trend = .005 ) . The association of physical activity level with maximum treadmill walking distance did not reach statistical significance ( P trend = .083 ) . There were no associations of physical activity with treadmill distance to onset of leg symptoms ( P trend = .795 ) . CONCLUSION Functional performance measures are more strongly associated with physical activity levels during daily life than treadmill walking measures", "OBJECTIVE To derive formulae to predict the likely 12-month health-related quality of life outcome following different treatments for intermittent claudication ( IC ) . DESIGN A prospect i ve , r and omized , controlled study . MATERIAL S One hundred and seventy-one unselected patients with stable IC were sequentially r and omized to invasive therapy , supervised physical training or observation . Hierarchical analysis was used to identify significant predictors of outcome . RESULTS The strongest outcome predictors were baseline values of the respective outcome variables in all groups . No more than two significant secondary predictors were identified for each outcome variable and no outcome variable was a predictor of any other outcome variable . Result ing prediction equations achieved between 61 and 90 % concordance with improvement ( 75 % considered adequate ) , with best prediction for invasive therapy and poorest for observation . Suggested cutpoints for the various endpoints in the three groups had sensitivities ranging between 65 and 100 % and false positive rates between 5 and 50 % . CONCLUSIONS The derived equations adequately predicted improvement on the various outcome variables in invasive therapy and supervised physical training , and may serve as aids in selecting patients likely to benefit most from a particular treatment strategy . The uniqueness of the outcome variables underscores the importance of implementing a comprehensive set of endpoints relevant to the impacts of the condition", "PURPOSE There is a need to evaluate patients with peripheral arterial disease ( PAD ) with a limited or extended walking distance . We aim ed to enable an estimation of walking distance as measured on a frequently used \" st and ard \" grade d ( 3.2 km·h(-1 ) , 2 % increase per 2 min ) protocol for walking distances measured on protocol s with a lower or higher workload . METHODS Patients with PAD and an absolute claudication distance ( ACD ) of \" st and ard \" protocol were included . Four grade d study treadmill protocol s , two with lower and two with higher workload than the \" st and ard \" protocol , were developed . Two study protocol s ( low or high ) and the \" st and ard \" protocol were repeated in r and om order . Quality was determined with the intraclass correlation coefficient and the coefficient of variation . Orthogonal regression analysis was used to predict walking distances on the st and ard protocol on the basis of the study protocol s. RESULTS Forty-three patients with an ACD Because feasibility from the protocol s with 2.0 km·h(-1 ) and 2 % increase every 2 min and 4.4 km·h(-1 ) and 2 % increase every minute was highest , they were calibrated against the \" st and ard \" protocol , and reliability was comparable with the \" st and ard \" protocol . The coefficient of variation between the prediction of walking distance on the \" st and ard \" protocol on the basis of the new protocol s and the measured distances were in the same range ( 22%-25 % ) as the variation measured performing the same treadmill test twice . CONCLUSIONS An accurate estimate of walking distance as measured on a \" st and ard \" treadmill protocol can be derived from a protocol with a lower or higher workload", "Background — Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication , supervised exercise ( SE ) , or stent revascularization ( ST ) . Methods and Results — We r and omly assigned 111 patients with aortoiliac peripheral artery disease to receive 1 of 3 treatments : optimal medical care ( OMC ) , OMC plus SE , or OMC plus ST . The primary end point was the change in peak walking time on a grade d treadmill test at 6 months compared with baseline . Secondary end points included free-living step activity , quality of life with the Walking Impairment Question naire , Peripheral Artery Question naire , Medical Outcomes Study 12-Item Short Form , and cardiovascular risk factors . At the 6-month follow-up , change in peak walking time ( the primary end point ) was greatest for SE , intermediate for ST , and least with OMC ( mean change versus baseline , 5.8±4.6 , 3.7±4.9 , and 1.2±2.6 minutes , respectively ; P Although disease-specific quality of life as assessed by the Walking Impairment Question naire and Peripheral Artery Question naire also improved with both SE and ST compared with OMC , for most scales , the extent of improvement was greater with ST than SE . Free-living step activity increased more with ST than with either SE or OMC alone ( 114±274 versus 73±139 versus −6±109 steps per hour ) , but these differences were not statistically significant . Conclusions — SE results in superior treadmill walking performance than ST , even for those with aortoiliac peripheral artery disease . The contrast between better walking performance for SE and better patient-reported quality of life for ST warrants further study . Clinical Trial Registration — URL : http:// clinical trials.gov/ct/show/NCT00132743?order=1 . Unique identifier : NCT00132743", "Background — This prospect i ve , r and omized , controlled clinical trial compared changes in exercise performance and daily ambulatory activity in peripheral artery disease patients with intermittent claudication after a home-based exercise program , a supervised exercise program , and usual-care control . Methods and Results — Of the 119 patients r and omized , 29 completed home-based exercise , 33 completed supervised exercise , and 30 completed usual-care control . Both exercise programs consisted of intermittent walking to nearly maximal claudication pain for 12 weeks . Patients wore a step activity monitor during each exercise session . Primary outcome measures included claudication onset time and peak walking time obtained from a treadmill exercise test ; secondary outcome measures included daily ambulatory cadences measured during a 7-day monitoring period . Adherence to home-based and supervised exercise was similar ( P=0.712 ) and exceeded 80 % . Both exercise programs increased claudication onset time ( P peak walking time ( P home-based exercise increased daily average cadence ( P0.05 ) . The changes in claudication onset time and peak walking time were similar between the 2 exercise groups ( P>0.05 ) , whereas the change in daily average cadence was greater with home-based exercise ( P home-based exercise program , quantified with a step activity monitor , has high adherence and is efficacious in improving claudication measures similar to a st and ard supervised exercise program . Furthermore , home-based exercise appears more efficacious in increasing daily ambulatory activity in the community setting than supervised exercise . Clinical Trial Registration — URL : http://www . Clinical Trials . Gov . Unique identifier : NCT00618670", "PURPOSE : The purpose of this study was to compare the effects of a 24-week walking with poles rehabilitation program with a traditional 24-week walking program on physical function in patients with peripheral arterial disease ( PAD ) . METHODS : Patients with PAD ( n = 103 , age = 69.7 ± 8.9 years , ankle-brachial index were r and omized into a rehabilitation program of traditional walking ( n = 52 ) or walking with poles ( n = 51 ) . Patients exercised 3 times per week for 24 weeks . Exercise endurance was measured by time walked on a constant work rate treadmill test at 6 , 12 , and 24 weeks . Perceived physical function was measured by the Medical Outcomes Study Short Form-36 and Walking Impairment Question naire . Tissue oxygenation was measured using near-infrared spectroscopy . RESULTS : Patients assigned to the traditional walking group walked longer at 24 weeks than those assigned to the pole walking group ( 21.10 ± 17.07 minutes and 15.02 ± 12.32 minutes , respectively , P = .037 ) . There were no differences between the groups in tissue oxygenation . However , there was a significant lengthening of time for which it took to reach minimum tissue oxygenation values ( P in perceived physical function as measured by the Physical Function subscale on the Medical Outcomes Study Short Form-36 or perceived walking distance as measured by the Walking Distance subscale on the Walking Impairment Scale . CONCLUSIONS : Traditional walking was superior to walking with poles in increasing walking endurance on a constant work rate treadmill test for patients with PAD", "PURPOSE The effects of upper-limb ( arm cranking ) and lower-limb ( leg cranking ) exercise training on walking distances in patients with intermittent claudication was assessed . METHODS Sixty-seven patients ( 33 to 82 years old ) with moderate to severe intermittent claudication were recruited , and the maximum power generated during incremental upper- and lower-limb ergometry tests was determined , as were pain-free and maximum walking distances ( by using a shuttle walk test ) . Patients were r and omly assigned to an upper-limb training group ( n = 26 ) or a lower-limb training group ( n = 26 ) . An additional untrained group ( n = 15 ) was recruited on an ad hoc basis in parallel with the main trial by using identical inclusion criteria . This group was subsequently shown to possess a similar demographic distribution to the two exercise groups . Supervised training sessions were held twice weekly for 6 weeks . RESULTS Both training programs significantly improved the maximum power generated during the incremental upper- and lower-limb ergometry tests ( P central cardiovascular function that was independent of the training mode . More importantly , pain-free and maximum walking distances also improved in both training groups ( P upper-limb exercise training may result , in part , from systemic cardiovascular effects rather than localized metabolic or hemodynamic changes . CONCLUSION Carefully prescribed upper-limb exercise training can evoke a rapid symptomatic improvement in patients with claudication , while avoiding the physical discomfort experienced when performing lower-limb weight-bearing exercise", "OBJECTIVE Determine the efficacy of a home-based walking intervention to improve walking ability and quality of life in people with diabetes and peripheral arterial disease ( PAD ) . RESEARCH DESIGN AND METHODS We conducted a r and omized , controlled , single-blind trial within university-affiliated clinics in our local community . We r and omized 145 participants ( 45 women ) with diabetes and PAD to our intervention — a 6-month behavioral intervention targeting levels of readiness to engage in routine walking for exercise — versus attention control . Our primary outcome was 6-month change in maximal treadmill walking distance . Secondary outcomes included 3-month change in maximal walking distance , lower limb function ( i.e. , walking impairment scores ) , quality of life ( Medical Outcomes Short Form Survey ) , exercise behaviors , depressive symptoms , and self-efficacy at 3 and 6 months . RESULTS The mean age of participants was 66.5 ( SD 10.1 ) years . Intervention and control groups did not differ significantly in 6-month change in maximal treadmill walking distance ( average [ SE ] 24.5 [ 19.6 ] meters vs. 39.2 [ 19.6 ] meters ; P = 0.60 ) . Among secondary outcomes , for the intervention and control groups , respectively , average walking speed scores increased by 5.7 [ 2.2 ] units and decreased by 1.9 [ 2.8 ] units ( P = 0.03 ) ; the mental health quality of life subscale score increased by 3.2 [ 1.5 ] and decreased by 2.4 [ 1.5 ] units ( P = 0.01 ) . CONCLUSIONS A home-based walking intervention did not improve walking distance but did improve walking speed and quality of life in people with diabetes and PAD . Clinicians should consider recommending home-based walking therapy for such patients", "BACKGROUND Serum markers of inflammation and platelet activation are related to cardiovascular risk . Cardiovascular risk reduction is a major treatment goal in patients with peripheral arterial disease ( PAD ) . Although current guidelines recommend supervised exercise training ( SET ) for PAD patients with intermittent claudication , its contribution to risk reduction remains unclear . Aim of the present study was to assess the impact of SET on inflammation and platelet activation as surrogates for cardiovascular risk . METHODS Fifty-three patients with intermittent claudication were r and omly assigned to SET on top of best medical treatment ( BMT ) for 6 months ( SET-group ) or to BMT only ( BMT-group ) . High sensitivity C-reactive protein ( hs-CRP ) , interleukin-6 ( IL-6 ) and fibrinogen as well as soluble P-selectin ( sP-sel ) , prothrombin fragment 1 + 2 ( F1.2 ) and monocyte-platelet aggregates ( MPA ) were determined at study entry , after 3 , 6 and 12 months . RESULTS While clinical improvement , reflected by an increase of walking capacity , was observed upon SET , no lasting changes of markers of inflammation and platelet activation were found within the SET-group during the training period . Compared to the BMT-group no improvements of these markers were observed in response to training at any time point ( all p > 0.05 ) . CONCLUSION Regular SET added no further anti-inflammatory effect and had no effect on platelet activation when provided on top of BMT in PAD patients with intermittent claudication", "Background This prospect i ve , r and omized , controlled clinical trial compared changes in primary outcome measures of claudication onset time ( COT ) and peak walking time ( PWT ) , and secondary outcomes of submaximal exercise performance , daily ambulatory activity , vascular function , inflammation , and calf muscle hemoglobin oxygen saturation ( StO2 ) in patients with symptomatic peripheral artery disease ( PAD ) following new exercise training using a step watch ( NEXT Step ) home‐exercise program , a supervised exercise program , and an attention‐control group . Methods and Results One hundred eighty patients were r and omized . The NEXT Step program and the supervised exercise program consisted of intermittent walking to mild‐to‐moderate claudication pain for 12 weeks , whereas the controls performed light resistance training . Change scores for COT ( P PWT ( P 6‐minute walk distance ( P=0.028 ) , daily average cadence ( P=0.011 ) , time to minimum calf muscle StO2 during exercise ( P=0.025 ) , large‐artery elasticity index ( LAEI ) ( P=0.012 ) , and high‐sensitivity C‐reactive protein ( hsCRP ) ( P=0.041 ) were significantly different among the 3 groups . Both the NEXT Step home program and the supervised exercise program demonstrated a significant increase from baseline in COT , PWT , 6‐minute walk distance , daily average cadence , and time to minimum calf StO2 . Only the NEXT Step home group had improvements from baseline in LAEI , and hsCRP ( P . Conclusions NEXT Step home exercise utilizing minimal staff supervision has low attrition , high adherence , and is efficacious in improving COT and PWT , as well as secondary outcomes of submaximal exercise performance , daily ambulatory activity , vascular function , inflammation , and calf muscle StO2 in symptomatic patients with PAD . Clinical Trial Registration URL : Clinical Trials.gov . Unique Identifier : NCT00618670", "OBJECTIVES Supervised exercise training ( SET ) is recommended for patients with intermittent claudication ( IC ) . The optimal exercise programme has not been identified , and the potential adverse effects of exercise on these patients warrant consideration . Calpain proteases have been linked with tissue atrophy following ischaemia-reperfusion injury . High calpain activity may therefore cause muscle wasting in claudicants undergoing SET , and skeletal muscle mass ( SMM ) is integral to healthy ageing . This study assesses the impact of ( 1 ) treadmill-based SET alone ; and ( 2 ) treadmill-based SET combined with resistance training on pain-free walking distance ( PFWD ) , SMM , and calpain activity . METHODS Thirty-five patients with IC were r and omised to 12 weeks of treadmill only SET ( group A ) , or combined treadmill and lower-limb resistance SET ( group B ) . PFWD via a 6-minute walking test , SMM via dual energy X-ray absorptiometry , and calpain activity via biopsies of gastrocnemius muscles were analysed . RESULTS Intention-to-treat analyses revealed PFWD improved within group A ( 160 m to 204 m , p = .03 ) , but not group B ( 181 m to 188 m , p = .82 ) . There was no between group difference ( p = .42 ) . Calpain activity increased within group A ( 1.62 × 10(5 ) fluorescent units [ FU ] to 2.21 × 10(5 ) FU , p = .05 ) , but not group B. There was no between group difference ( p = .09 ) . SMM decreased within group A ( -250 g , p = .11 ) and increased in group B ( 210 g , p = .38 ) ( p = .10 between groups ) . Similar trends were evident for per protocol analyses , but , additionally , change in SMM was significantly different between groups ( p = .04 ) . CONCLUSIONS Neither exercise regimen was superior in terms of walking performance . Further work is required to investigate the impact of the calpain system on SMM in claudicants undertaking SET ", "Background and Objective : Type 2 diabetes is one of the main causes of peripheral vascular disease . The beneficial effects of exercise on glucose homeostasis include a marked stimulation of blood glucose utilization during and after its performance . The objective of this study was to determine the effects of a program of 3 physical therapy modalities on blood circulation in patients with type 2 diabetes with peripheral arterial disease . Subjects and Method : A r and omized controlled trial was undertaken . Sixty-eight patients with type 2 diabetes with Leriche-Fontaine stage I or IIa peripheral arterial disease were r and omly assigned to an exercise or placebo group . For 20 weeks , the exercise group underwent treatment comprising 3 exercises at proximal , medium , and distal segments of the lower limbs , and the placebo group received sham treatment with disconnected ultrasound equipment . Peripheral arterial disease was determined by evaluating the ankle/brachial index ( ABI ) , Doppler flow velocity , blood parameters , cardiovascular risk score , and heart rate during exercise test . Results : After 20 weeks of treatment , significant differences between groups were found in the following : right ( P ABI ; Doppler flow velocity ( cm/s ) in the right ( P posterior tibial artery and in the right ( P dorsalis pedis artery ; and fibrinogen ( P hemoglobin ( P cholesterol ( P high-density lipoprotein cholesterol ( P HbA1c ( P low-density lipoprotein cholesterol values ( P physical therapy modalities improves ABI , Doppler flow velocity , and blood parameters in patients with type 2 diabetes", "Calf claudication is the major clinical manifestation of peripheral vascular occlusive disease in a significant number of patients . Although claudication causes substantial patient disability , most patients are treated conservatively because of the risks of surgical therapy and the uncertain efficacy of drug therapy . It was hypothesized that rocker-soled shoes would decrease the work of the plantar flexors and therefore increase walking distance in patients with calf claudication . To test this hypothesis , walking distances in patients with calf claudication using rocker-soled shoes and a placebo shoe insert were compared . Rocker-soled shoes significantly increased both the total distance walked and the distance at which patients were initially bothered by symptoms by 77 m ( 37 % , p less than .0005 ) and 89 m ( 91 % , p = .003 ) , respectively . It was concluded that rocker-soled shoes may reduce disability in patients with calf claudication by increasing walking distance", "The effects of physical exercise on 8 stage II peripheral vascular disease ( PVD ) patients were observed after a six-month training program . Doppler velocimetry ( including the treadmill test ) , strain gauge plethysmography , and transcutaneous oxygen pressure were used to quantify the results , which were compared with those obtained in a control group of another 8 stage II PVD patients , under placebo therapy for six months . The results show physical exercise increased the walking capacity , both the pain-free walking time and the maximum walking time . No significant difference was observed in the other parameters studied , in either the exercise patients or the control group", "OBJECTIVES To evaluate effects of a structured home-based exercise program on functional capacity and quality of life ( QoL ) in patients with intermittent claudication ( IC ) after 1-year follow-up , and to compare these results with those from a concurrent control group who received supervised exercise training ( SET ) . DESIGN Comparative longitudinal cohort study . SETTING Referral center . PARTICIPANTS Patients ( N=142 ) with IC . INTERVENTIONS Structured home-based exercise training or SET . MAIN OUTCOME MEASURES The maximum ( pain-free ) walking distance and the ankle-brachial index ( ABI ) ( at rest and postexercise ) were measured at baseline and after 6 and 12 months ' follow-up . Additionally , QoL was evaluated using a self-administered question naire consisting of the Euroqol-5D ( scale 0 - 1 ) , rating scale ( scale 0 - 100 ) , Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ; scale 0 - 100 ) , and the Vascular Quality of Life Question naire ( VascuQol ; scale 1 - 7 ) . Comparison of the groups was performed with adjustment for the nonr and omized setting using propensity scoring . RESULTS One hundred forty-two patients with IC started the structured home-based exercise program , of whom 95 ( 67 % ) completed 12 months ' follow-up . The mean relative improvement compared with baseline was statistically significant after 12 months ' follow-up for the maximum and pain-free walking distance ( 342 % , 95 % confidence interval [ CI ] , 169 - 516 ; P ABI postexercise ( mean change , .06 ; 95 % CI , .01-.10 ; P=.02 ) . For the QoL outcomes , the improvement compared with baseline was statistically significant after 12 months for the VascuQol ( mean change , .42 ; 95 % CI , .20-.65 ; P SF-36 physical functioning ( mean change , 5.17 ; 95 % CI , .77 - 9.56 ; P=.02 ) . Compared with the structured home-based exercise program , patients in the control group showed significantly better results in the mean relative improvement of maximum and pain-free walking distance and change in the ABI at rest after 12 months ' follow-up . CONCLUSIONS Structured home-based exercise training is effective in improving both functional capacity and QoL in patients with IC and may be considered as a feasible and valuable alternative toSET , since supervised exercise programs are not often available", "OBJECTIVES To investigate the effects of exercise training on levels of circulating biomarkers associated with the progression of atherosclerosis and risk of cardiovascular events in patients with intermittent claudication . METHODS Circulating levels of soluble adhesion molecules ( sVCAM-1 , sICAM-1 , sE-selectin ) , high sensitivity C-reactive protein ( hs-CRP ) and stress proteins ( Hsp60 and Hsp70 ) in patients r and omised to a 24-week programme of arm- or leg-cranking exercise were compared with those in usual care controls . RESULTS Arm and leg exercise similarly improved lower-limb aerobic exercise capacity ( 20 % vs 19 % , respectively ; P maximum walking distance ( 30 % vs 35 % , respectively ; P training limb-specific peak oxygen consumption were attenuated for patients in the highest vs lowest quartile for circulating sVCAM-1 levels at baseline ( 3 % vs 25 % respectively , P circulating hs-CRP levels tended to be lower in the arm-cranking group ( -1.55 [ 95 % CI : -1.06 to -2.26]mgl(-1 ) ) , exercise training had no effect on circulating levels of soluble adhesion molecules or stress proteins . CONCLUSIONS These findings suggest that high levels of circulating sVCAM-1 are associated with an attenuated exercise training response and that arm-cranking exercise may provide an effective stimulus for evoking systemic anti-inflammatory adaptations in patients with intermittent claudication", "OBJECTIVES The main aims of treatment in patients with intermittent claudication ( IC ) are to improve the clinical indicators of lower limb ischaemia and patients ' quality of life ( QoL ) . The aims of this study were assess the clinical and cost effectiveness of a supervised exercise programme ( SEP ) in patients with IC . DESIGN Non-r and omised , controlled trial . SETTING University teaching hospital . PATIENTS AND METHODS Two groups of patients with IC were studied . Seventy patients were sequentially recruited before and after the establishment of a Supervised Exercise Programme at our unit . Thirty-seven patients ( median age 69 years , 26 men ) received conservative medical therapy ( CMT ) and 33 patients ( median age 67 years , 22 men ) received CMT plus a 3 month SEP of graduated physical exercise for sixty minutes , three times each week . Patients were assessed prior to and at 6 months following treatment . At each assessment patient reported walking distances ( PRWD ) , treadmill claudication and maximal distances ( ICD and MWD ) , ankle brachial pressure indices ( ABPI ) pre & post exercise and patient reported QoL using the SF36 question naire were assessed . RESULTS Prior to intervention the two groups were well matched . Following treatment , CMT patients demonstrated no significant change in PRWD or ICD but did record a small but significant improvement in MWD . CMT was also associated with a negative effect size in the SF36 index and in 7 of the 8 SF36 QoL domains , effect size > -0.5 for the domains of Physical Function and Emotional Role . SEP patients demonstrated significant improvement in PRWD , ICD and MWD . SEP was associated with a positive effect size in the SF36 index and in 2 SF36 QoL domains but a negative effect size in a further 2 domains . However , all QoL effect sizes following SEP were 0.5 for the SF36 domains of Physical Function , Physical Role , Emotion Role and SF36 index . SEP result ed in a 0.027 quality adjusted life year ( QALY ) gain over CMT in the first year post-treatment thus the cost/QALY gained of SEP is pound1780 at 1 year . CONCLUSIONS Compared to CMT , SEP increases walking distances , improves QoL and is a highly cost-effective treatment for IC", "The purpose of this study was to evaluate the efficacy of a pain-free treadmill walking program in intellectually disabled ( ID ) adults with arterial occlusive disease . Fourteen participants with mild ID participated in the walking program . Six patients showed stable intermittent claudication . A control ( nontreadmill , n = 12 ) group consisted of 4 individuals with intermittent claudication . Noninvasive determinations of lower-limb hemodynamics included photoplethysmography and ankle-brachial pressure . Pain levels were measured according to a pain pathophysiology index . The treadmill program consisted of individually prescribed low-endurance walking at a 0 % incline done at a comfortable speed 3 times per week . All participants completed the 15-week walking program and showed significant improvements ( p walking speed , distance , and duration . Pain levels were reduced in individuals suffering from intermittent claudication . Blood hemodynamic parameters also showed significant improvements . In conclusion , low-intensity treadmill walking significantly improved the functional capacities of adult individuals with mild ID with vascular occlusion and reduced pain levels", "The effects of 14-day physical exercise or iloprost treatment ( 0.5 - 2 ng/Kg/min ) on endogenous nitric oxide production and neutrophil adhesion were evaluated in 20 patients with peripheral arterial occlusive disease ( Fontaine Stage II ) . Peripheral venous blood sample s and 4-h urine sample s were collected before , immediately after 14 days of therapy and 7 - 10 days after therapy in order to evaluate neutrophil adhesion , nitrite/nitrate and cGMP excretion rates . A longer pain free walking distance was observed after exercise , compared to iloprost ( > 500 m in 3/10 subjects ) . Urinary nitrite/nitrate , as well as cGMP concentrations , significantly increased after exercise . Nitrite/nitrate excretion rate inversely correlated to neutrophil adhesion . No variations were observed in these parameters in iloprost treated patients . The improvement in claudication and the transient increase in urinary nitrite/nitrate suggest a possible nitric oxide-dependent mechanism for the clinical efficacy of physical exercise . The results from the present and previous observations indicate that , besides pharmacological treatments , a regular aerobic exercise improves peripheral arterial occlusive disease", "PURPOSE To determine if improvements in physical function and peripheral circulation after 6 months of exercise rehabilitation could be sustained over a subsequent 12-month maintenance exercise program in older patients with intermittent claudication . METHODS Seventeen patients r and omized to exercise rehabilitation and 14 patients r and omized to usual care control completed this 18-month study . Patients exercised three times per week during the first 6 months of a progressive exercise program , followed by two times per week during the final 12 months of a maintenance program . Patients were studied at baseline , 6 months , and 18 months during the study . RESULTS Eighteen months of exercise rehabilitation increased the initial claudication distance by 373 meters ( 189 % ) ( P absolute claudication distance by 358 meters ( 80 % ) ( P walking economy by 11 % ( P 6-minute walk distance by 10 % ( P daily physical activity by 31 % , and maximal calf blood flow by 18 % ( P exercise rehabilitation ( P = NS ) , and were significantly greater than the changes in the control group throughout the study ( P Improvements in claudication distances , walking economy , 6-minute walk distance , physical activity level , and peripheral circulation after 6 months of exercise rehabilitation are sustained for an additional 12 months in older patients with intermittent claudication using a less frequent exercise maintenance program", "OBJECTIVE To compare the effect of two training programmes and advice to exercise at home on physiological adaptations in patients with peripheral arterial disease ( PAD ) . DESIGN 30 patients with a typical history of PAD and intermittent claudication were r and omised to either an upper body strength training programme ( UBST ) , a dynamic ( walking , cycling , circuit ) conventional exercise rehabilitation programme ( CER ) , or advice to ' walk as much as possible at home ' ( CONT ) . Before and after intervention groups performed a st and ard grade d treadmill exercise test ( GTET ) and a 6-minute walk test ( SMWT ) to determine peak physiological parameters and walking distances . Maximal walking distance ( MWD ) , pain-free walking distance ( PFWD ) , peak oxygen uptake ( VO2 ) , heart rate and perceived pain were measured . RESULTS MWD on the GTET increased significantly in the CER group compared with the CONT and UBST groups ( 93.9 + /- 79 % v. 7.0 + /- 19.8 % v. 7.3 + /- 46 % ; CER v. UBST v. CONT p = 0.003 ) . Similarly , peak VO2 increased with CER compared with the CONT and UBST groups ( 28.4 + /- 20 v. -6.2 + /- 15 v. -1.0 + /- 21 % ; CER v. UBST v. CONT p = 0.004 ) . During the SMWT the CER and UBST groups improved in PFWD compared with the CONT group ( 37 + /- 47 % v. 27 + /- 71 % v. -30 + /- 29 % ; CER v. UBST v. CONT p = 0.03 ) , and perceived pain decreased in the CER group compared with the UBST group ( -24 + /- 39 % v. 27 + /- 48 % ; CER v. UBST p = 0.01 ) . CONCLUSION CER improves physiological parameters and walking distances more than UBST does . CER is effective within 6 weeks . Verbal encouragement to exercise is an ineffective form of management", "INTRODUCTION PAD medical therapy has a number of limitations . RLX showed promises in experimental model mainly through NO release . Our study is the first to evaluate the efficacy and safety of RLX in PAD . MATERIAL S- METHODS Eligible PAD La fontaine IIa-IIb patients were r and omized in 2 groups . Group A was treated with physical therapy plus oral pRLX , 20 ug b.i.d for 12 weeks , group B received physical therapy alone . Pain Free Walking Distance ( PFWD ) and Maximum Walking Distance ( MWD ) at 3 and 12 wks and at follow up 3 months after treatment interruption were performed . RESULTS The percentage increases of PFWD in group B were 23 + /- 9 , 65 + /- 17 , and 35 + /- 4 respectively at 3 and at 12 weeks , and 3 months after termination . In Group A showed significantly higher percentage increases : 74 + /- 16 p MWD in the B group were 29 + /- 7 , 55 + /- 10 and 54 + /- 8 at the above time points , while in the A group were 55 + /- 10 p RLX patients referred a better physical and mental status . No adverse events during or after the treatment were recorded . COMMENT RLX result ed very effective in PAD . Our results may suggest that the observed functional benefits should come not only from hemodynamic improvement but also from positive vascular remodeling", "The purpose of this study was to examine the effects of a 6-month exercise program on submaximal walking economy in individuals with peripheral arterial disease and intermittent claudication ( PAD-IC ) . Participants ( n = 16 ) were r and omly allocated to either a control PAD-IC group ( CPAD-IC , n = 6 ) which received st and ard medical therapy , or a treatment PAD-IC group ( TPAD-IC ; n = 10 ) which took part in a supervised exercise program . During a grade d treadmill test , physiological responses , including oxygen consumption , were assessed to calculate walking economy during submaximal and maximal walking performance . Differences between groups at baseline and post-intervention were analyzed via Kruskal – Wallis tests . At baseline , CPAD-IC and TPAD-IC groups demonstrated similar walking performance and physiological responses . Postintervention , TPAD-IC patients demonstrated significantly lower oxygen consumption during the grade d exercise test , and greater maximal walking performance compared to CPAD-IC . These preliminary results indicate that 6 months of regular exercise improves both submaximal walking economy and maximal walking performance , without significant changes in maximal walking economy . Enhanced walking economy may contribute to physiological efficiency , which in turn may improve walking performance as demonstrated by PAD-IC patients following regular exercise programs", "OBJECTIVE : To verify the acute effects of resistance exercise on post‐exercise blood pressure in patients with intermittent claudication . METHODS : Eight patients r and omly underwent two experimental sessions : a session of resistance exercise ( R : 6 exercises , 3 sets of 12 , 10 and 8 reps with a perceived exertion of 11 to 13 on the 15‐ grade Borg scale ) and a control session ( C : resting on exercise machines ) . RESULTS : Before and for 60 min following an intervention , auscultatory blood pressure was measured while subjects rested in a sitting position . After the C session , systolic , diastolic and mean blood pressures did not change from the pre‐intervention values , while these values decreased significantly after the R session throughout the entire recovery period ( greatest decreases = ‐14±5 , ‐6±5 , and ‐9±4 mmHg , respectively , P of resistance exercise patients with intermittent claudication exhibited reduced systolic , diastolic and mean blood pressures , suggesting that acute resistance exercise may decrease cardiovascular load in these patients", "Background We studied whether a 6‐month group‐mediated cognitive behavioral ( GMCB ) intervention for peripheral artery disease ( PAD ) participants , which promoted home‐based walking exercise , improved 6‐minute walk and other outcomes at 12‐month follow‐up , 6 months after completing the intervention , compared to a control group . Methods and Results We r and omized PAD participants to a GMCB intervention or a control group . During phase I ( months 1 to 6 ) , the intervention used group support and self‐regulatory skills during weekly on‐site meetings to help participants adhere to home‐based exercise . The control group received weekly on‐site lectures on topics unrelated to exercise . Primary outcomes were measured at the end of phase I. During phase II ( months 7 to 12 ) , each group received telephone contact . Compared to controls , participants r and omized to the intervention increased their 6‐minute walk distance from baseline to 12‐month follow‐up , ( from 355.4 to 381.9 m in the intervention versus 353.1 to 345.6 m in the control group ; mean difference=+34.1 m ; 95 % confidence interval [CI]=+14.6 , + 53.5 ; P speed score ( from 36.1 to 46.5 in the intervention group versus 34.9 to 36.5 in the control group ; mean difference = + 8.8 ; 95 % CI=+1.6 , + 16.1 ; P=0.018 ) . Change in the WIQ distance score was not different between the 2 groups at 12‐month follow‐up ( P=0.139 ) . Conclusions A weekly on‐site GMCB intervention that promoted home‐based walking exercise intervention for people with PAD demonstrated continued benefit at 12‐month follow‐up , 6 months after the GMCB intervention was completed . Clinical Trial Registration URL : Clinical Trials.gov . Unique identifier : NCT00693940", "This r and omized trial proposed to determine if there were differences in calf muscle StO2 parameters in patients before and after 12 weeks of a traditional walking or walking-with-poles exercise program . Data were collected on 85 patients who were r and omized to a traditional walking program ( n = 40 ) or walking-with-poles program ( n = 45 ) of exercise training . Patients walked for 3 times weekly for 12 weeks . Seventy-one patients completed both the baseline and the 12-week follow-up progressive treadmill tests ( n = 36 traditional walking and n = 35 walking-with-poles ) . Using the near-infrared spectroscopy measures , StO2 was measured prior to , during , and after exercise . At baseline , calf muscle oxygenation decreased from 56 ± 17 % prior to the treadmill test to 16 ± 18 % at peak exercise . The time elapsed prior to reaching nadir StO2 values increased more in the traditional walking group when compared to the walking-with-poles group . Likewise , absolute walking time increased more in the traditional walking group than in the walking-with-poles group . Tissue oxygenation decline during treadmill testing was less for patients assigned to a 12-week traditional walking program when compared to those assigned to a 12-week walking-with-poles program . In conclusion , the 12-week traditional walking program was superior to walking-with-poles in improving tissue deoxygenation in patients with PAD", "In a comparative study the authors report on results of series of physical therapy in disturbances of the peripheral arterial blood supply . Examined were the behaviour of blood pressure , the painless walking distance and the peripheral microcirculation with the xenon-133-muscle clearance method before and after treatments lasting 10 to 12 weeks with combined exercises consisting of gymnastics and walking according to the interval principle ( twice a week ) , with sauna visits twice a week as well as before and after diadynamic series of the current . In all therapy groups an improvement of the peripheral haemodynamics could be statistically ascertained . The distance of the intermittent claudication prolonged particularly in the group with interval walking . In the walking group and in the sauna group the values of the systolic blood pressure were significantly reduced . Side-effects were not observed . Therapy effects of the series of physical therapy described are best to be proved by the xenon-133 muscle clearance", "BACKGROUND The first-line intervention for intermittent claudication is usually supervised exercise therapy ( SET ) . The literature describes a range of exercise programs varying in setting , duration , and content . The purpose of the present study was to examine the exercise protocol s offered and to identify the impact of the intensity of the SET programs ( in terms of frequency , duration , and type of exercise ) on improvements in walking distance ( response ) in the first 3 months . The present study is part of the Exercise Therapy in Peripheral Arterial Disease ( EXITPAD ) study , a multicenter r and omized clinical trial comparing the effects of SET provided by regional physiotherapists , with or without daily feedback , on the level of activities with the effects of walking advice . METHODS The analysis included patients r and omized to receive SET with or without feedback . The physical therapists administering the SET were asked to fill out therapy evaluation sheets stating frequency , duration , and type of exercises . The relationship between training volume and the impact on walking distance was explored by dividing training volume data into tertiles and relating them to the median change in maximum walking distance at 3 and 12 months . RESULTS Data of 169 patients were included in the analysis . A SET program consisting of at least two training sessions per week each lasting over 30 minutes , during the first 3 months of a 1-year program tailored to individual patients ' needs led to better results in terms of walking distance after 3 and 12 months than the other variants . The results of our analysis dividing training volume into tertiles suggest that there is a relationship between training volume and improvement in walking distance and that at least 590 minutes of training should be offered in the first 3 months . No differences were found between program involving only walking and a combination of exercises , nor between individual and group training . CONCLUSION A SET programs consisting of at least two training sessions a week , each lasting over 30 minutes , should be offered during the first 3 months of the SET program to optimize improvement in terms of maximum walking distance", "In a cross-over trial with 114 patients , intravenous Actovegin or an oral placebo were administered in addition to basic physiotherapy . In the evaluation 105 of the subjects were taken into consideration . It was shown that the test group ( n = 53 ) achieved a 12 % increase in walking distance ( measured in the st and ardized walking distance test ) compared with the placebo group ( n = 52 ) . The therapeutic success rate , i.e. the evaluation base for the efficacy of basic physiotherapy was comparatively good and statistically confirmed at 69.8 % and 73.1 % for the two groups . From this it may be concluded that basic physiotherapy can be effectively supported by Actovegin", "Purpose : Peripheral arterial disease ( PAD ) is a chronic , progressive disease with a significant cardiovascular and cerebrovascular risk burden and a considerable impact on functional capacity and quality of life ( QoL ) . Exercise programmes result in significant improvements in walking distances but long-term effects are uncertain . The aim of this study was to assess the one-year effects of participation in a 12-week supervised exercise programme on functional capacity and QoL for PAD patients . Methods : Patients were r and omly allocated to a control ( n = 16 ) or an exercise ( n = 28 ) group . Data regarding functional capacity ( Walking Impairment Question naire WIQ ) , disease-specific QoL ( Intermittent Claudication Question naire ICQ ) and generic QoL ( SF-36 ) were collected at baseline , 12 weeks and 1 year . Results : At 12 weeks , there was a trend towards improved QoL in both groups , with a tendency for greater improvement in the exercise group ( p = 0.066 ) and a trend towards improved functional capacity ( WIQ Stair-climbing p = 0.093 ) in the exercise group . At 1 year , ICQ scores in the exercise group were considerably better than those in the control group ( p = 0.058 ) , reflecting improved QoL and maintenance of benefits . Conclusions : Participation in a supervised exercise programme results in improvements in functional capacity and QoL at 1 year post-participation . Implication s for Rehabilitation Peripheral arterial disease has a considerable impact on functional capacity and quality of life Functional capacity and quality of life are improved in patients with peripheral arterial disease up to 1 year post-participation in supervised exercise Improvements at 1 year are reduced from those noted immediately following an exercise", "OBJECTIVE To examine the influence of peripheral arterial disease ( PAD ) on heart rate variability ( HRV ) in patients , and to examine the influence of an intense long-term ( 12 months ) exercise program on HRV in PAD patients . METHODS This study involved ambulatory patients attending a local hospital and university center . Participants were twenty-five patients with diagnosed PAD and intermittent claudication and 24 healthy , age-matched adults . Interventions involved r and om allocation of PAD patients to 12 months of conservative medical treatment ( Conservative ) or medical treatment with supervised treadmill walking ( Exercise ) . The main outcome measures were time- and frequency-domain , nonlinear HRV measures during supine rest , and maximal walking capacity prior to and following the intervention . RESULTS Despite significantly worse walking capacity ( 285 ± 190 m vs 941 ± 336 m ; P , Exercise patients exhibited a significantly greater improvement in walking capacity ( 183 % ± 185 % vs 57 % ± 135 % ; P = .03 ) with similar small nonsignificant changes in HRV compared with Conservative patients . CONCLUSIONS The current study demonstrated that PAD patients exhibited similar resting HRV to healthy adults with 12 months of intense supervised walking producing similar HRV changes to that of conservative medical treatment . The greater walking capacity of healthy adults and PAD patients following supervised exercise does not appear to be associated with enhanced HRV", "PURPOSE This study aim ed to investigate the acute effect of intermittent walking exercise ( WE ) on blood pressure ( BP ) responses in patients with intermittent claudication ( IC ) . Secondly , this study aim ed to gain improved insight into the physiological mechanisms controlling BP regulation after intermittent WE in this patient group . METHODS Twenty patients with IC participated in two experimental sessions in a r and om order , as follows : WE ( 15 × 2-min bouts of WE interpolated with 2-min rest intervals ) and control ( st and ing rest on a treadmill for 60 min ) . BP , cardiac output ( CO : CO2 rebreathing ) , and cardiovascular autonomic modulation ( spectral analysis of HR variability ) were assessed before and after both experimental sessions during supine rest , and stroke volume ( SV ) and systemic vascular resistance ( SVR ) were calculated . Data were analyzed using two-way ANOVA . RESULTS WE decreased systolic , diastolic , and mean BP , with net effects of -13 ± 2 , -5 ± 2 , and -7 ± 2 mm Hg versus control , respectively ( all P ) . WE also decreased SV ( -5.62 ± 1.97 mL , P increase in SVR in the control condition ( + 4.2 ± 1.4 U , P HR showed a decrease ( P increased vagal modulation , in the control condition . BP measurements over the subsequent 24 h were similar between experimental conditions . CONCLUSIONS In patients with IC , WE induced a postexercise hypotension response that had a significant magnitude versus control but was not maintained over the next 24 h of daily activities . The acute postexercise hypotension response was mediated by a decrease in CO and SV , which was not compensated by an augmentation of SVR , as observed in the control arm of the study", "PURPOSE The purpose of this r and omized trial was to compare the efficacy of a low-intensity exercise rehabilitation program vs a high-intensity program in changing physical function , peripheral circulation , and health-related quality of life in peripheral arterial disease ( PAD ) patients limited by intermittent claudication . METHODS Thirty-one patients r and omized to low-intensity exercise rehabilitation and 33 patients r and omized to high-intensity exercise rehabilitation completed the study . The 6-month exercise rehabilitation programs consisted of intermittent treadmill walking to near maximal claudication pain 3 days per week at either 40 % ( low-intensity group ) or 80 % ( high-intensity group ) of maximal exercise capacity . Total work performed in the two training regimens was similar by having the patients in the low-intensity group exercise for a longer duration than patients in the high-intensity group . Measurements of physical function , peripheral circulation , and health-related quality of life were obtained on each patient before and after the rehabilitation programs . RESULTS After the exercise rehabilitation programs , patients in the two groups had similar improvements in these measures . Initial claudication distance increased by 109 % in the low-intensity group ( P absolute claudication distance increased by 61 % ( P peak oxygen uptake , ischemic window , and health-related quality of life . CONCLUSION The efficacy of low-intensity exercise rehabilitation is similar to high-intensity rehabilitation in improving markers of functional independence in PAD patients limited by intermittent claudication , provided that a few additional minutes of walking is accomplished to elicit a similar volume of exercise", "BACKGROUND The prothrombotic , hypofibrinolytic state that develops in patients with intermittent claudication ( IC ) upon walking due to ischemia-reperfusion injury ( IRI ) of the leg muscles may contribute to the high incidence of life- and limb-threatening thrombotic events observed in this patient group . Treatments , such as angioplasty , that obtund the IRI also ameliorate the procoagulant diathesis . The effect on this diathesis of supervised exercise and cilostazol , both of which provide symptomatic benefit in IC , but without significantly obtunding IRI , is unknown . METHODS Thirty-four patients ( 27 men and 7 women ; median age , 67 years ; range , 63 - 72 years ) were r and omized to receive best medical therapy ( BMT ) plus supervised exercise ( n = 9 ) , BMT plus cilostazol ( n = 9 ) , BMT plus supervised exercise plus cilostazol ( n = 7 ) , or BMT alone ( n = 9 ) in a 2 x 2 factorial design . Thrombin-antithrombin complex and prothrombin fragments 1 and 2 , both markers of thrombin generation ; plasminogen activator inhibitor antigen and tissue plasminogen activator antigen , both markers of fibrinolysis ; ankle-brachial pressure index ( ABPI ) ; and initial and absolute claudication distance ( ACD ) were measured at baseline and then 3 and 6 months after r and omization . RESULTS At 6 months , when compared with receiving BMT only , supervised exercise and cilostazol result ed in improvements in ABPI of 18 % and 13 % and in ACD of 40 % and 64 % , respectively . The effects on ABPI and ACD of combining supervised exercise and cilostazol were additive . Supervised exercise , cilostazol , and supervised exercise combined with cilostazol had no significant effect on any of the four hemostatic markers . CONCLUSIONS Treatment of IC by supervised exercise or cilostazol results in significant improvements in ABPI and ACD but has no demonstrable effect on the prothrombotic diathesis . This suggests that supervised exercise and cilostazol , unlike angioplasty , are unlikely to have a long-term beneficial effect on the thrombotic risks faced by these patients", "BACKGROUND The optimal first-line treatment for intermittent claudication is currently unclear . OBJECTIVE To compare the cost-effectiveness of endovascular revascularization vs supervised hospital-based exercise in patients with intermittent claudication during a 12-month follow-up period . DESIGN R and omized controlled trial with patient recruitment between September 2002-September 2006 and a 12-month follow-up per patient . SETTING A large community hospital . PARTICIPANTS Patients with symptoms of intermittent claudication due to an iliac or femoro-popliteal arterial lesion ( 293 ) who fulfilled the inclusion criteria ( 151 ) were recruited . Excluded were , for example , patients with lesions unsuitable for revascularization ( iliac or femoropopliteal TASC-type D and some TASC type-B/C. INTERVENTION Participants were r and omly assigned to endovascular revascularization ( 76 patients ) or supervised hospital-based exercise ( 75 patients ) . MEASUREMENTS Mean improvement of health-related quality -of-life and functional capacity over a 12-month period , cumulative 12-month costs , and incremental costs per quality -adjusted life year ( QALY ) were assessed from the societal perspective . RESULTS In the endovascular revascularization group , 73 % ( 55 patients ) had iliac disease vs 27 % ( 20 patients ) femoral disease . Stents were used in 46/71 iliac lesions ( 34 patients ) and in 20/40 femoral lesions ( 16 patients ) . In the supervised hospital-based exercise group , 68 % ( 51 patients ) had iliac disease vs 32 % ( 24 patients ) with femoral disease . There was a non-significant difference in the adjusted 6- and 12-month EuroQol , rating scale , and SF36-physical functioning values between the treatment groups . The gain in total mean QALYs accumulated during 12 months , adjusted for baseline values , was not statistically different between the groups ( mean difference revascularization versus exercise 0.01 ; 99 % CI -0.05 , 0.07 ; P = .73 ) . The total mean cumulative costs per patient was significantly higher in the revascularization group ( mean difference euro2318 ; 99 % CI 2130 euros , 2506 euros ; P incremental cost per QALY was 231 800 euro/QALY adjusted for the baseline variables . One-way sensitivity analysis demonstrated improved effectiveness after revascularization ( mean difference 0.03 ; CI 0.02 , 0.05 ; P incremental costs 75 208 euro/QALY . CONCLUSION In conclusion , there was no significant difference in effectiveness between endovascular revascularization compared to supervised hospital-based exercise during 12-months follow-up , any gains with endovascular revascularization found were non-significant , and endovascular revascularization costs more than the generally accepted threshold willingness-to-pay value , which favors exercise", "This study aims to evaluate the reliability of repeated grade d workload treadmill testing ( G-test ; 2 mph ; 0 % grade , increasing 2 % every 2 min ) and to compare the reliability of a constant workload treadmill protocol ( C-test ; 2 mph ; 12 % grade ) versus the grade d workload treadmill protocol in patients with intermittent claudication , studied longitudinally . A clinical trial investigating an orally stable prostacycline derivative that included 330 patients with intermittent claudication was performed . The trial employed three active treatment groups and one placebo group . Because there were no significant inter-group differences at baseline or after treatment , data from all groups were pooled for the evaluation of treadmill test reliability . Treadmill data were obtained from a 2-week run-in phase where three G-tests were performed , as well as from the beginning and the end of a 3-month double-blind phase where a G-test and a C-test were performed in r and om order . Treadmill test reliability was described through test process-related and between-subject variances and also using variance-derived parameters such as the reliability coefficient ( RC ) and the relative precision ( RP ) . A higher value for the RC and a lower value for the RP indicate that the test variability is predominantly due to between-subject variance and not to test process-related variance . Estimates of variance were described for both the maximal or absolute claudication distance ( ACD ) and the initial claudication distance ( ICD ) with each treadmill test . Reliability estimates are reported for the total study sample and for patients with baseline claudication distances diseased claudicants . Theoretical considerations suggest that reliability measures may differ in these subgroups . With repeated testing during the run-in phase for the measure of ACD , the G-test had an RC of 0.952 and an RP of 21.9 % . With the comparison of both test protocol s in the entire study population for the measurement of ACD , the G-test had an RC of 0.902 and an RP of 31.3 % , while the C-test had an RC of 0.876 and an RP of 35.2 % . The results for ICD on the G-test were an RC of 0.809 and an RP of 43.7 % , while the C-test had an RC of 0.737 and an RP of 51.3 % . The reliability of the ACD measurement for RC and RP was numerically superior to those for the ICD for both protocol s. In patients with a baseline ACD , the RC for ACD on the G-test was 0.827 and the RP was 41.4 % . In contrast , on the C-test the RC decreased to 0.250 and the RP increased to 86.6 % . These changes in RC and RP were due to a marked decrease in the between-subject variance , demonstrating the inability of the C-test to separate appropriately the different claudication distances in population s with highly limited baseline claudication distances . During a run-in phase , the G-test has excellent test characteristics . During the longitudinal phase of a trial , the reliability of G-tests and C-tests are comparable in the entire study population . However , in patients with low claudication distances , the G-test should be given preference over the C-test", "OBJECTIVE The purpose of the study was to examine the effects of a 12-month exercise program on lower limb mobility ( temporal-spatial gait parameters and gait kinematics ) , walking performance , peak physiological responses , and physical activity levels in individuals with symptoms of intermittent claudication due to peripheral arterial disease ( PAD-IC ) . METHODS Participants ( n = 21 ) with an appropriate history of PAD-IC , ankle-brachial pressure index ( ABI ) Participants were r and omly allocated to either a control PAD-IC group ( CPAD-IC ) ( n = 11 ) that received st and ard medical therapy and a treatment PAD-IC group ( TPAD-IC ) ( n = 10 ) , which also took part in a 12-month supervised exercise program . A further group of participants ( n = 11 ) free of PAD ( ABI > 0.9 ) and who were non-regular exercisers were recruited from the community to act as age and mass matched controls ( CON ) . Lower limb mobility was determined via two-dimensional video motion analysis . A grade d treadmill test was used to assess walking performance and peak physiological responses to exercise . Physical activity levels were measured via a 7-day pedometer recording . Differences between groups were analyzed via repeated measures analysis of variance ( ANOVA ) . RESULTS The 12-month supervised exercise program had no significant effect on lower limb mobility , peak physiological responses , or physical activity levels in TPAD-IC compared with CPAD-IC participants . However , the TPAD-IC participants demonstrated significantly greater walking performance ( 171 % improvement in pain free walking time and 120 % improvement in maximal walking time compared with baseline ) . CONCLUSION The results of this study confirm that a 12-month supervised exercise program will result in improved walking performance , but does not have an impact on lower limb mobility , peak physiological responses , or physical activity levels of PAD-IC patients", "Functional impairment , functional decline , and mobility loss are major public health problems in people with lower extremity peripheral artery disease ( PAD ) . Few medical therapies significantly improve walking performance in PAD . We describe methods for the PROgenitor cell release Plus Exercise to improve functionaL performance in PAD ( PROPEL ) Study , a r and omized controlled clinical trial design ed to determine whether granulocyte-macrophage colony stimulating factor ( GM-CSF ) combined with supervised treadmill walking exercise improves six-minute walk distance more than GM-CSF alone , more than supervised treadmill exercise alone , and more than placebo plus attention control in participants with PAD , respectively . PROPEL Study participants are r and omized to one of four arms in a 2 by 2 factorial design . The four study arms are GM-CSF plus supervised treadmill exercise , GM-CSF plus attention control , placebo plus supervised exercise therapy , or placebo plus attention control . The primary outcome is change in six-minute walk distance at 12-week follow-up . Secondary outcomes include change in brachial artery flow-mediated dilation ( FMD ) , change in maximal treadmill walking time , and change in circulating CD34 + cells at 12-week follow-up . Outcomes are also measured at six-week and six-month follow-up . Results of the PROPEL Study will have important implication s for underst and ing mechanisms of improving walking performance and preventing mobility loss in the large and growing number of men and women with PAD", "PURPOSE This study was performed to test the effectiveness of a formal supervised exercise program against a home-based exercise program for both walking ability and quality of life endpoints . METHODS Patients with arterial claudication were r and omized to either a 12-week supervised exercise program ( SUPEX ) with weekly lectures relating to peripheral vascular disease or to a home exercise group ( HOMEX ) who attended an identical lecture program and received weekly exercise instruction . The study population included 29 men and 26 women , with a mean age of 69.1 + /- 8.1 years . Forty-seven patients completed the 12-week program , 46 were available for testing at completion , and 38 for 6-month testing . Claudication pain time ( CPT ) and maximum walking time ( MWT ) on a progressive treadmill exercise test were assessed at baseline , program completion , and 6 months . The Medical Outcomes Study Short Form-36 ( SF-36 ) was administered at these intervals to assess effects on quality of life . RESULTS Each group improved ( p CPT and MWT at the completion of the 12-week program , which was sustained at the 6-month follow-up . Increase in HOMEX CPT from baseline ( 3.6 + /- 2.73 minutes ) to 6-month follow-up ( 6.6 + /- 3.17 minutes ) was less than for the SUPEX group ( 3.8 + /- 2.74 to 11.2 + /- 4.02 minutes , respectively ) ; similar results were obtained for MWT . At both completion and 6 months , there was a significant intergroup difference for CPT and MWT ( p health perception based on the SF-36 demonstrated improvement ( p Physical Function Subscale , Bodily Pain Subscale , and Physical Composite Score . There were no between-group differences on the subsets of the SF-36 at the three assessment intervals . CONCLUSIONS Supervised exercise programs provide superior increased walking ability in the noninterventional therapy of arterial claudication , and both supervised and home based exercise therapy result in improved SF-36 functional measures . The lack of intergroup differences in these measures may be a result of the high degree of interaction with healthcare providers in the HOMEX group . Although a supervised program results in optimal walking benefits , a highly structured home-based program provides similar functional improvement and may be a satisfactory alternative for patients with lesser walking requirements", "The aim of this r and omized study was to compare the reliability of the treadmill test at constant-load ( C-test , 3 km/hr ; fixed grade of 12 % ) recommended in Germany with that of the grade d-exercise test ( G-test , 3 km/hr ; increase in grade of 3.5 % every 3 minutes ) propagated in the United States . In 50 patients with an absolute claudication distance ( ACD ) in the C-test of between 50 and 400 m , the two treadmill tests were carried out in r and omized order on one and the same day , and repeated on 3 days within 1 week . For the initial claudication distance ( ICD ) , the intraclass correlation was 0.88 in the C-test and 0.87 in the G-test . For the ACD the coefficients were identical at 0.91 . The within-subject variation ( CVwithin ) in the C-test and G-test was 25 % and 27 % for the ICD and for the ACD 24 % and 21 % , respectively . The between-subject variation was very similar with 72 % and 73 % ( ICD ) and with 78 % and 68 % ( ACD ) . However , in ACDs below 100 m and between 100 to 150 m , the C-test showed significantly smaller coefficients of variation than the G-test : 13 % vs 81 % and 14 % vs 50 % , respectively . In conclusion , the results showed that both C-test and G-test are equally well reproducible", "In the treatment of peripheral obliterating arteriopathy ( POA ) physical training provides clear results in terms of increased walking autonomy ; it is still not fully clear whether the positive effects of physical training can be further improved by concomitant back-up drug therapy . For this purpose 374 patients of both sexes , with a mean age of 64 years , suffering from chronic peripheral obliterating arteriopathy of the lower limbs were enrolled in a controlled open clinical trial , instructed to follow a programme of physical training and r and omly allocated to low dose treatment with heparin calcium ( 12,500 IU/day ) for 6 months . An improvement in the claudicometric parameters ( free gait interval , absolute gait interval and recovery time ) measured at constant speed and in the resting Winsor ankle/arm index of the most severely damaged limb were observed in both groups . These improvements were significantly greater in the group receiving pharmacological treatment ( p heparin calcium at low doses in association with a physical training programme in patients suffering from Fontaine 's stage II peripheral obliterating arteriopathy", "PURPOSE The purpose of this investigation was to evaluate the efficacy of PoleStriding exercise ( a form of walking that uses muscles of the upper and lower body in a continuous movement similar to cross-country skiing ) and vitamin E ( alpha-tocopherol ) to improve walking ability and perceived quality of life ( QOL ) of patients with claudication pain secondary to peripheral arterial disease ( PAD ) . METHODS Fifty-two subjects were r and omized into four groups : PoleStriding with vitamin E ( N = 13 ) , PoleStriding with placebo ( N= 14 ) , vitamin E without exercise ( N= 13 ) , and placebo without exercise ( N = 12 ) . The dose of vitamin E was 400 IU daily . Only the PoleStriding with vitamin E and PoleStriding with placebo groups received PoleStriding instruction and training . Assignment to vitamin E or placebo was double blind . Subjects trained three times weekly for 30 - 45 min ( rest time excluded ) . Individuals in vitamin E and placebo groups came to the laboratory biweekly for ankle blood-pressure measurements . RESULTS Results of this r and omized clinical trial provide strong evidence that PoleStriding significantly ( P exercise tolerance on the constant work-rate and incremental treadmill tests . Ratings of perceived claudication pain were significantly less after the PoleStriding training program ( P= 0.02 ) . In contrast , vitamin E did not have a statistically significant effect on the subjects ' ratings of perceived leg pain ( P= 0.35 ) or treadmill walking duration ( P= 0.36 ) . Perceived distance and walking speed ( Walking Impairment Question naire ) and perceived physical function ( R and Short Form-36 ) improved in the PoleStriding trained group only ( P PoleStriding effectively improved the exercise tolerance and perceived QOL of patients with PAD . Little additional benefit to exercise capacity was realized from vitamin E supplementation", "PURPOSE To compare clinical success , functional capacity , and quality of life during 12 months after revascularization or supervised exercise training in patients with intermittent claudication . MATERIAL S AND METHODS This study had institutional review board approval , and all patients gave written informed consent . Between September 2002 and September 2005 , 151 consecutive patients who presented with symptoms of intermittent claudication were r and omly assigned to undergo either endovascular revascularization ( angioplasty-first approach ) ( n = 76 ) or hospital-based supervised exercise ( n = 75 ) . The outcome measures were clinical success , functional capacity , and quality of life after 6 and 12 months . Clinical success was defined as improvement in at least one category in the Rutherford scale above the pretreatment level . Significance of differences between the groups was assessed with the unpaired t test , chi(2 ) test , or Mann-Whitney U test . To adjust outcomes for imbalances of baseline values , multivariable regression analysis was performed . RESULTS Immediately after the start of treatment , patients who underwent revascularization improved more than patients who performed exercise in terms of clinical success ( adjusted odds ratio [ OR ] , 39 ; 99 % confidence interval [ CI ] : 11 , 131 ; P signs of ipsilateral symptoms at 6 months compared with patients in the exercise group ( adjusted OR , 0.4 ; 99 % CI : 0.2 , 0.9 ; P functional capacity and quality of life scores increased after 6 and 12 months , but no significant differences between the groups were demonstrated . CONCLUSION After 6 and 12 months , patients with intermittent claudication benefited equally from either endovascular revascularization or supervised exercise . Improvement was , however , more immediate after revascularization", "OBJECTIVES To compare the effect of unsupervised exercise , supervised exercise and intermittent pneumatic foot and calf compression ( IPC ) on the claudication distance , lower limb arterial haemodynamics and quality of life of patients with intermittent claudication . METHODS Thirty-four eligible patients with stable intermittent claudication were r and omised to IPC ( n = 13 , 3h/d for 6 months ) , supervised exercise ( n = 12 , three hourly sessions/week for 6 months ) or unsupervised exercise ( n = 9 ) . In each patient , initial claudication distance ( ICD ) , absolute claudication distance ( ACD ) , resting ankle brachial pressure index ( ABPI ) , and resting hyperaemic calf arterial inflow were measured before , 6 weeks , 6 months and 1 year after r and omisation . Quality of life was assessed with the short form (SF)-36 , walking impairment ( WIQ ) and intermittent claudication question naires ( ICQ ) . RESULTS Compared with unsupervised exercise , both IPC and supervised exercise , increased ICD and ACD , up to 2.83 times . IPC increased arterial inflow ( p ABPI . Supervised exercise decreased arterial inflow and increased ABPI ( p Unsupervised exercise had no effect on arterial inflow or ABPI . IPC improved significantly the ICQ score and the speed score of the WIQ , while supervised exercise improved the WIQ claudication severity score . At 1 year clinical effectiveness of supervised exercise and IPC was largely preserved . CONCLUSIONS IPC , by augmenting leg perfusion , achieved improvement in walking distance comparable with supervised exercise . Long-term results in a larger number of patients will provide valuable information on the optimal treatment modality of intermittent claudication", "In a non-r and omized , open-label study results after a structured institution-based peripheral arterial occlusive disease ( PAD ) rehabilitation program were compared with the results of training at home . Three groups were compared : group 1 ( n = 19 ) PAD rehabilitation ; group 2 ( n = 19 ) PAD rehabilitation + clopidogrel 75 mg once daily ; group 3 ( n = 21 ) home-based training . The training period was 3 months for all groups , which was followed by a 3-month observation phase ( without prescribed training ) . The rehabilitation program consisted of 3 training hours per week . Background variables , demographics , and baseline claudication distances were comparable between groups . After 3 months of training the absolute claudication distances ( ACD ) improved by 82.7 % , 131.4 % , and 5.4 % for groups 1 , 2 and 3 . The initial claudication distances ( ICD ) changed by 163.8 % , 200.6 % , and 44.4 % , respectively . All changes , except the ACD result for group 3 , were statistically significant ( p 0.05 ) . Structured training groups ( 1 and 2 ) performed significantly better than group 3 ( p 0.05 ) . When results from groups 1 and 2 were pooled , ACDs changed from 493.3 218.1 to 1026.0 468.9 m , 546.0 378.8 m [ 95 % CI 417.8 - 674.2 m ] ; p 0.05 . ICDs improved from 175.3 110.8 m to 493.1 326.7 m , 320.8 315.9 m [ 95 % CI 213.9 - 427.7 m ] ; p 0.05 . The difference between the pooled mean results of the structured training groups and the results of group 3 amounted to 474.3 m [ 95 % CI 270.2 - 678.4 m ] and 242.4 m [ 95 % CI 99.0 - 385.7 m ] , for ACD and ICD , respectively . Structured , supervised PAD rehabilitation is a highly efficacious treatment for intermittent claudication and may be regarded as the present gold st and ard among conservative treatment options", "The hypothesis that smoking has an acute effect on treadmill exercise per formance in patients with peripheral vascular disease was investigated in a crossover trial . Twelve patients with stable intermittent claudication who were regular smokers attended on two occasions within one week and treadmill tests were performed after 1/2 , 1 , 1½ , and 2 hours . Immediately before the second exercise test , two st and ard cigarettes were smoked or an unlit cigarette was \" sham-smoked . \" Because participants could not be blinded , an attempt to con trol for patient bias was made . Half were told that we expected smoking to make no difference or possibly cause some improvement , and half were told that we expected it to make no difference or possibly cause some deterioration . These explanations and the order of study days were determined by balanced r and om ization . Suggestion had a significant influence on claudication distance immediately after smoking ( p on walking distance . Combin ing data from both groups assumes that no overall bias was introduced by the explanations given . Immediately after smoking , small , nonsignificant increases in claudication distance ( + 10 % , 95 % CI-7 % , + 27 % ) and walking distance ( + 9 % , 95 % CI-2 % , + 19 % ) were observed . Smoking caused a mean increase in heart rate of 9 beats per minute , which persisted for one hour , but no consistent change in blood pressure . The results show that suggestion may have a signifi ca nt influence on treadmill exercise distances . Smoking is unlikely to have an important acute effect on exercise performance in claudicants", "PURPOSE This study was performed to test the efficacy of a supervised , hospital-based exercise program compared with a home-based exercise program involving minimal supervision , for both walking ability and quality of life measures in patients with exercise-limiting intermittent leg claudication . METHODS Twenty-one patients were assigned r and omly to 12 weeks of supervised exercise or to a home-based exercise group . After 12 weeks the participants in the supervised group transitioned to a home-based program . Both groups were then reevaluated at the end of 24 weeks . The initial claudication distance ( ICD ) and absolute claudication distance ( ACD ) on progressive treadmill exercise was measured at baseline , 12 weeks , and 24 weeks . Additionally , self-reported quality of life status was evaluated using the MOS SF-36 question naire . RESULTS Each group improved ( P ACD from baseline to 12 weeks , which was sustained at the 24-week follow-up . Both groups experienced similar long-term improvements ( P ACD ( 521.5 + /- 253.4 meters to 741.9 + /- 365.6 meters for the supervised group , 532.2 + /- 263.5 meters to 715.0 + /- 394.4 meters in the home group , P not significant , between groups ) . The supervised group experienced a greater improvement ( P ICD after 12 weeks than the home group but not at 24 weeks . The on-site group also experienced significant improvements in ICD after 24 weeks ( P self-reported physical function or mental health as assessed by the MOS SF-36 . CONCLUSION A structured exercise program was more effective in improving the ICD over a 24-week period than a less formal , home-based program . However , if patients are screened properly and receive adequate instruction , a home-based program can be a safe , low-cost alternative providing similar long-term ( 24 weeks ) exercise benefits in ACD", "Background : Lifestyle modification is associated with a substantially decreased risk of cardiovascular events . However , the role of lifestyle intervention for secondary prevention in patients with noncardioembolic ischemic stroke is inadequately defined . We assessed the hypothesis that lifestyle intervention can reduce the onset of new vascular events in patients with noncardioembolic mild ischemic stroke . Methods : We conducted an observer-blind r and omized controlled trial that enrolled 70 patients ( 48 men , mean age 63.5 years ) with acute noncardioembolic mild ischemic stroke . The patients were allocated in equal numbers to a lifestyle intervention group or a control group . We performed lifestyle interventions , which comprised exercise training , salt restriction and nutrition advice for 24 weeks . Then all patients were prospect ively followed up for occurrence of the primary endpoints , including hospitalization due to stroke recurrence and the onset of other vascular events . We also evaluated systolic blood pressure ( SBP ) at the clinic and at home , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , hemoglobin A1c ( HbA1c ) and high-sensitivity C-reactive protein ( hs-CRP ) to compare the efficacy of the lifestyle interventions . Results : This trial was terminated earlier than expected because of the prespecified early stopping rule for efficacy . After the 24-week intervention period , the intervention group showed a significant increase in daily physical activity and a significant decrease in salt intake ( physical activity , p = 0.012 ; salt intake , p blood pressure was decreased and the HDL-C levels were increased in the intervention group ( SBP , p LDL-C , HbA1c and hs-CRP tended to decrease in the intervention group , but this decrease did not achieve significance . After a median follow-up period of 2.9 years , 12 patients allocated to the control group and 1 patient in the lifestyle intervention group experienced at least 1 vascular event . A sequential plans analysis indicated the superiority of the lifestyle intervention in interim analysis . Kaplan-Meier survival curves after the log-rank test showed a significant prognostic difference between the r and omized groups ( p = 0.005 ) . Conclusions : Lifestyle intervention with appropriate medication is beneficial for reducing the incidence of new vascular events and improving vascular risk factors in patients with noncardioembolic mild ischemic stroke", "OBJECTIVES to compare the effect of surgery , exercise and simple observation on maximum exercise power in claudicants . DESIGN prospect i ve , r and omised study . METHODS a total of 264 unselected claudicants were r and omised to supervised exercise training , invasive treatment ( open surgical or endovascular procedures ) or observation . One year treatment outcomes were analysed on an intention to-treat basis . RESULTS invasively treated patients showed a significant improvement in maximum walking power , stopping distance , post-ischaemic blood flow and big toe pressure at one year . Patients r and omised to physical exercise training or to the control group did not improve in any outcome measure . CONCLUSION invasive treatment increased walking capacity , leg blood pressure and flow . Supervised physical exercise training offered no therapeutic advantage compared to untreated controls", "BACKGROUND Although there have been many studies showing that exercise training is beneficial for patients with peripheral vascular occlusive disease ( PVOD ) , there is little research comparing various modes of training . Previous studies showed that exercise tests performed on a StairMaster ( StairMaster Sports/Medical Products , Kirkl and , WA ) produce responses similar to those elicited by treadmill tests . The purpose of this study was to compare these modes of exercise in a training program for patients with PVOD . METHODS Of the 23 eligible individuals who began the exercise program , 11 did not complete the regimen due to various complications . Thus , 12 patients were r and omly assigned to train for 12 weeks on either a StairMaster ( n = 6 ) or a treadmill ( n = 6 ) . Patients underwent progressive and single-stage exercise tests on both exercise modalities before and after training . RESULTS Mean exercise time before the onset of claudication pain for all tests rose significantly after training ( P treadmill exercise performance with less improvement noted when tested on the StairMaster , and vice versa ) . Exercise time to maximal pain increased for the training apparatus only ( P foot transcutaneous oxygen tension or the ankle-brachial blood pressure index . CONCLUSIONS Both StairMaster and treadmill training improve the exercise capacity of PVOD patients . The training effect is most apparent for the specific training apparatus , but there is some cross-over improvement to the other exercise modality . Thus , StairMaster training is appropriate and can be part of the exercise prescription for treatment of these patients", "PURPOSE In patients with intermittent claudication ( IC ) a structured walking exercise program improves exercise performance . However , few studies have evaluated the effects of exercise training on functional status during daily activities . We hypothesized that a supervised exercise training program would improve functional status in patients with IC , with 24 weeks of training more beneficial than 12 weeks . A secondary aim was to evaluate the effects of strength training and combinations of strength and treadmill training on functional status . METHODS Twenty-nine men with disabling IC were r and omized to 12 weeks of either supervised treadmill training ( 3 hr/wk at a work intensity sufficient to produce claudication ) , strength training ( 3 hr/wk of resistive training of six muscle groups of each leg ) , or to a nonexercising control group . Functional status was assessed by question naires characterizing walking ability ( Walking Impairment Question naire , WIQ ) , habitual physical activity level ( Physical Activity Recall , PAR ) , and physical , social , and role functioning , well-being , and overall health ( Medical Outcomes Study SF-20 , MOS ) . Patients alos had their activity levels monitored with an activity monitor ( Vitalog ) . RESULTS After 12 weeks of treadmill training PAR scores increased by 48 metabolic equivalent hr/wk , the MOS physical functioning score by 24 percentage points , and the number of bouts of walking activity measured by the Vitalog by 4.5 bouts/hr ( all p WIQ scores . After 12 additional weeks of treadmill training improvements initially observed in the PAR , MOS , and Vitalog scores were maintained , and in addition the ability to walk distances ( WIQ ) improved by 31 percentage points , and the IC severity score had improved by 29 percentage points ( both p strength training patients improved their WIQ walking speed , stair climbing scores , and MOS well-being scores with no other changes in functional status . Subjects in the control group did not improve functional status by any measure . Twelve weeks of treadmill training after the strength training program maintained WIQ walking speed scores , and activity level defined by Vitalog improved . Twelve weeks of combined treadmill and strength training after the control period had no effect on functional status . CONCLUSIONS A supervised treadmill training program improved functional status during daily activities , with 24 weeks more effective than 12 . In addition , treadmill training alone was more effective in improving functional status in patients with IC than strength training or combinations of the training modalities", "OBJECTIVES To determine if the use of a plantar flexion device ( Step It pedal ) in a newly developed exercise programme is of benefit to patients with peripheral arterial disease . DESIGN Prospect i ve feasibility trial with patients r and omised to either st and ard care or the Step It exercise programme plus st and ard care . SETTING Physiotherapy Department at Cumberl and Infirmary , Carlisle , UK . PARTICIPANTS Patients were identified from the vascular team 's referral list . In total , 42 patients agreed to take part ; 18 in the control group and 24 in the intervention group . INTERVENTIONS Eligible participants were r and omised and received either st and ard care or took part in a plantar flexion resistance exercise programme , involving the Step It pedal , for a period of 12 weeks . MAIN OUTCOME MEASURES Maximum walking distance , claudication distance and ankle brachial pressure index . RESULTS Eighty-three percent of patients completed the study . Improvements in median distance to claudication symptoms and maximum walking distance were observed in the intervention group but not in the control group . Nine out of 15 ( 60 % ) participants in the control group and 14 out of 20 ( 70 % ) participants in the intervention group improved their walking distance . Ankle brachial pressure index remained virtually unchanged in both groups . CONCLUSIONS Due to the variability of patients ' fitness in the sample , it can not be concluded whether use of the Step It pedal has additional benefits to patients over st and ard care . However , the study completion rate implies that patients with peripheral arterial disease are receptive to undertaking exercise programmes", "Mika P , Spodaryk K , Cencora A , Unnithan VB , Mika A : Experimental model of pain-free treadmill training in patients with claudication . Am J Phys Med Rehabil 2005;84:756–762 . Objective : Treadmill training in claudication is often based on walking exercise to a pain threshold or longer to the maximum muscle pain of the lower limbs . This kind of exercise may cause an inflammatory response . The purpose of this study was to determine whether pain-free treadmill training using walking exercise to 85 % of the distance to onset of claudication pain can significantly improve pain-free walking distance in patients with intermittent claudication and to evaluate whether this kind of program may induce an inflammatory response leading to the progression of atherosclerosis . Design : A total of 98 patients aged 50–70 yrs with stable intermittent claudication were r and omized into a supervised treadmill training program or a comparison group . Patients in the treatment group participated in 12 wks of supervised treadmill training . We examined the effects of 12 wks of pain-free treadmill training on pain-free walking distance , total leukocyte count , neutrophil count , and microalbuminuria in patients with claudication . Results : A total of 80 participants completed the program . Exercise rehabilitation increased the time to onset of claudication pain by 119.2 % , from 87.4 ± 38 m to 191.6 ± 94.8 m ( P in total leukocyte count , neutrophil count , or microalbuminuria after 12 wks of treadmill exercise ( P > 0.05 ) Conclusion : A pain-free training program can be used in the treatment of claudication as a low-risk program , increasing walking ability without potential harmful effects of ischemia – reperfusion injury", "BACKGROUND To explore the efficacy of cycle training in the treatment of intermittent claudication , the present study compared performance and physiologic effects of cycle training with more conventional treadmill walking training in a group of patients with claudication . METHOD Forty-two individuals with peripheral arterial disease and intermittent claudication ( 24 men , 18 women ) were stratified by gender and the presence or absence of type 2 diabetes mellitus and then r and omized to a treadmill ( n = 13 ) , cycle ( n = 15 ) , or control group ( n = 14 ) . Treadmill and cycle groups trained three times a week for 6 weeks , whereas the control group did not train during this period . Maximal and pain-free exercise times were measured on grade d treadmill and cycle tests before and after training . RESULTS Treadmill training significantly improved maximal and pain-free treadmill walking times but did not improve cycle performance . Cycle training significantly improved maximal cycle time but did not improve treadmill performance . However , there was evidence of a stronger cross-transfer effect between the training modes for patients who reported a common limiting symptom during cycling and walking at baseline . There was also considerable variation in the training response to cycling , and a subgroup of responsive patients in the cycle group improved their walking performance by more than the average response observed in the treadmill group . CONCLUSION These findings suggest that cycle exercise is not effective in improving walking performance in all claudication patients but might be an effective alternative to walking in those who exhibit similar limiting symptoms during both types of exercise", "Platelet function and levels of vascular adhesion molecule-1 ( VCAM-1 ) were investigated in 24 patients with peripheral arterial disease at Fontaine stage II undergoing a 2 weeks treatment with iloprost ( 0.5 - 2 ng/kg/h i.v . infused , 6 h/day ) or a 2 weeks supervised physical training , r and omly assigned . Patients were studied before ( T0 ) and after ( T14 ) treatments and 10 days later ( T24 ) . The adhesion of washed platelets to fibrinogen coated microwells was reduced after treatment both with iloprost ( 1.9+/-0.4 vs 6.8+/-0.7 % ; T24 vs T0 ; M+/-SEM ; p adhesion to human plasma coated microwells was reduced only after treatment with iloprost ( 1.9+/-0.8 vs 5.8+/-0.9 ; p expression of fibrinogen receptor ( glycoprotein IIb/IIIa ) on platelets , measured by flow-cytometry was also reduced after iloprost treatment ( 17.1+/-1.5 vs 31.8+/-4.8 AU ; p of platelet thromboxane A2 metabolite 2,3-dinor-thromboxane B2 decreased only in patients treated with iloprost ( 154.7+/-97.9 vs 256.2+/-106.4 pg mg creatinine(-1 ) ; p plasma VCAM-1 was lower in patients who were treated with iloprost ( 827.7+/-77.4 vs 999.0+/-83.8 ng ml(-1 ) ; p iloprost and physical exercise seem to act on reversible phenomena such as the expression of adhesion molecules or ex vivo adhesion , whereas only iloprost reduces thromboxane A2 bio synthesis in vivo . This anti-platelet activity seems to be extended in time and to be associated with an improvement in vascular function", "BACKGROUND Supervised exercise training ( SET ) is recommended as initial treatment to improve walking capacity in peripheral arterial disease ( PAD ) patients with intermittent claudication . Various mechanisms by which SET yields beneficial effects are postulated , however data regarding its influence on angiogenesis are scarce . Thus , we design ed a prospect i ve r and omized controlled trial to study the impact of SET on markers of angiogenesis and endothelial function in PAD . METHODS Forty PAD patients were r and omized to SET on top of best medical treatment ( SET+BMT ) for 6 months versus best medical treatment ( BMT ) only . Endothelial progenitor cells ( EPC ) were assessed by whole-blood flow cytometry ( co-expression of CD34 + CD133 + KDR+ ) and cell culture assays ( endothelial cell-colony forming units , circulating angiogenic cells , migration assay ) at baseline , 3 , 6 and 12-months after inclusion . Changes of plasma levels of asymmetric dimethylarginine ( ADMA ) , vascular endothelial growth factor ( VEGF ) , stromal cell-derived factor-1 ( SDF-1 ) and maximum walking distance were determined . RESULTS EPC - measured by flow cytometric and cell culture techniques - increased significantly upon training paralleled by a significant decrease of ADMA when compared to the BMT group ( p beneficial effect of SET on EPC diminished , but maximum walking distance was significantly improved compared to baseline and controls ( p VEGF and SDF-1 plasma levels in time course . CONCLUSIONS SET increases circulating EPC counts and decreases ADMA levels reflecting enhanced angiogenesis and improved endothelial function , which might contribute to cardiovascular risk reduction", "Introduction : Peripheral atherosclerotic disease ( PAD ) is a condition characterized by low functional capacity which is associated with impaired free living , ambulation and low exercise tolerance . The purpose of this r and omized controlled study was to evaluate whether changes in maximal walking time are associated with adaptations in cardiovascular function following supervised exercise", "OBJECTIVE This r and omized controlled trial investigated the effects of upper- and lower-limb aerobic exercise training on disease-specific functional status and generic health-related quality of life ( QOL ) in patients with intermittent claudication . METHODS The study recruited 104 patients ( mean age , 68 years ; range , 50 - 85 ) from the Sheffield Vascular Institute . Patients were r and omly allocated to groups that received upper-limb ( ULG ) or lower-limb ( LLG ) aerobic exercise training , or to a nonexercise control group . Exercise was performed twice weekly for 24 weeks at equivalent limb-specific relative exercise intensities . Main outcome measures were scores on the Walking Impairment Question naire ( WIQ ) for disease-specific functional status , the Medical Outcomes Study Short Form version 2 ( SF-36v2 ) , and European Quality of Life Visual Analog Scale ( EQ-VAS ) for health-related QOL . Outcomes were assessed at baseline , and at 6 , 24 , 48 , and 72 weeks . RESULTS After 6 weeks , improvements in the perceived severity of claudication ( P = .023 ) and stair climbing ability ( P = .011 ) vs controls were observed in the ULG , and an improvement in the general health domain of the SF-36v2 vs controls was observed in the LLG ( P = .010 ) . After 24 weeks , all four WIQ domains were improved in the ULG vs controls ( P ≤ .05 ) , and three of the four WIQ domains were improved in the LLG ( P health-related QOL domains were apparent in the ULG . CONCLUSIONS These findings support the use of alternative , relatively pain-free forms of exercise in the clinical management of patients with intermittent claudication", "Expansion of the capillary network , or angiogenesis , occurs following endurance training . This process , which is reliant on the presence of VEGF ( vascular endothelial growth factor ) , is an adaptation to a chronic mismatch between oxygen dem and and supply . Patients with IC ( intermittent claudication ) experience pain during exercise associated with an inadequate oxygen delivery to the muscles . Therefore the aims of the present study were to examine the plasma VEGF response to acute exercise , and to establish whether exercise training alters this response in patients with IC . In Part A , blood was collected from patients with IC ( n=18 ) before and after ( + 20 and + 60 min post-exercise ) a maximal walking test to determine the plasma VEGF response to acute exercise . VEGF was present in the plasma of patients ( 45.11+/-29.96 pg/ml ) and was unchanged in response to acute exercise . Part B was a training study to determine whether exercise training altered the VEGF response to acute exercise . Patients were r and omly assigned to a treatment group ( TMT ; n=7 ) that completed 6 weeks of high-intensity treadmill training , or to a control group ( CON ; n=6 ) . All patients completed a maximal walking test before and after the intervention , with blood sample s drawn as for Part A. Training had no effect on plasma VEGF at rest or in response to acute exercise , despite a significant increase in maximal walking time in the TMT group ( 915+/-533 to 1206+/-500 s ; P=0.009 ) following the intervention . The absence of a change in plasma VEGF may reflect altered VEGF binding at the endothelium , although this can not be confirmed by the present data", "CONTEXT Neither supervised treadmill exercise nor strength training for patients with peripheral arterial disease ( PAD ) without intermittent claudication have been established as beneficial . OBJECTIVE To determine whether supervised treadmill exercise or lower extremity resistance training improve functional performance of patients with PAD with or without claudication . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled clinical trial performed at an urban academic medical center between April 1 , 2004 , and August 8 , 2008 , involving 156 patients with PAD who were r and omly assigned to supervised treadmill exercise , to lower extremity resistance training , or to a control group . MAIN OUTCOME MEASURES Six-minute walk performance and the short physical performance battery . Secondary outcomes were brachial artery flow-mediated dilation , treadmill walking performance , the Walking Impairment Question naire , and the 36-Item Short Form Health Survey physical functioning ( SF-36 PF ) score . RESULTS For the 6-minute walk , those in the supervised treadmill exercise group increased their distance walked by 35.9 m ( 95 % confidence interval [ CI ] , 15.3 - 56.5 m ; P distance walked by 12.4 m ( 95 % CI , -8.42 to 33.3 m ; P = .24 ) compared with the control group . Neither exercise group improved its short physical performance battery scores . For brachial artery flow-mediated dilation , those in the treadmill group had a mean improvement of 1.53 % ( 95 % CI , 0.35%-2.70 % ; P = .02 ) compared with the control group . The treadmill group had greater increases in maximal treadmill walking time ( 3.44 minutes ; 95 % CI , 2.05 - 4.84 minutes ; P walking impairment distance score ( 10.7 ; 95 % CI , 1.56 - 19.9 ; P = .02 ) ; and SF-36 PF score ( 7.5 ; 95 % CI , 0.00 - 15.0 ; P = .02 ) than the control group . The resistance training group had greater increases in maximal treadmill walking time ( 1.90 minutes ; 95 % CI , 0.49 - 3.31 minutes ; P = .009 ) ; walking impairment scores for distance ( 6.92 ; 95 % CI , 1.07 - 12.8 ; P = .02 ) and stair climbing ( 10.4 ; 95 % CI , 0.00 - 20.8 ; P = .03 ) ; and SF-36 PF score ( 7.5 ; 95 % CI , 0.0 - 15.0 ; P = .04 ) than the control group . CONCLUSIONS Supervised treadmill training improved 6-minute walk performance , treadmill walking performance , brachial artery flow-mediated dilation , and quality of life but did not improve the short physical performance battery scores of PAD participants with and without intermittent claudication . Lower extremity resistance training improved functional performance measured by treadmill walking , quality of life , and stair climbing ability . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00106327", "OBJECTIVES To describe recruitment to a r and omised controlled trial of a 12-week ( twice-weekly ) supervised exercise programme for patients with peripheral arterial disease ( PAD ) . PAD is a chronic , progressive disease with a significant cardiovascular and cerebrovascular risk burden , and exercise is an effective primary management approach . METHOD Potential patients were identified from the Non-Invasive Vascular Laboratory records and invited to participate in the study . On successful completion of an incremental treadmill exercise test , patients were allocated at r and om to a control ( usual care ) or an exercise group . RESULTS Between November 2006 and June 2009 , 548 patients were identified . Of the 156 patients who met the inclusion criteria , 40 ( 26 % ) declined to participate . Of the 71 patients who underwent exercise testing , 23 ( 32 % ) did not complete the test . The final enrolment number was 44 ( 44/156 ; 28 % ) . Eleven patients ( 11/28 ; 39 % ) subsequently withdrew from the exercise programme . CONCLUSION Recruitment to clinical trials of exercise presents significant challenges in the PAD population due to the presence of co-existing cardiovascular and cerebrovascular disease , a reluctance to exercise due to leg pain , and an acceptance of reduced mobility as part of ageing . Early identification in primary care before the onset of significant comorbidity may ameliorate some of these issues", "OBJECTIVE To analyze the effects of strength training ( ST ) in walking capacity in patients with intermittent claudication ( IC ) compared with walking training ( WT ) effects . METHODS Thirty patients with IC were r and omized into ST and WT . Both groups trained twice a week for 12 weeks at the same rate of perceived exertion . ST consisted of three sets of 10 repetitions of whole body exercises . WT consisted of 15 bouts of 2-minute walking . Before and after the training program walking capacity , peak VO(2 ) , VO(2 ) at the first stage of treadmill test , ankle brachial index , ischemic window , and knee extension strength were measured . RESULTS ST improved initial claudication distance ( 358 + /- 224 vs 504 + /- 276 meters ; P total walking distance ( 618 + /- 282 to 775 + /- 334 meters ; P VO(2 ) at the first stage of treadmill test ( 9.7 + /- 2.6 vs 8.1 + /- 1.7 mL.kg(-1).minute ; P ischemic window ( 0.81 + /- 1.16 vs 0.43 + /- 0.47 mm Hg minute meters(-1 ) ; P = .04 ) , and knee extension strength ( 19 + /- 9 vs 21 + /- 8 kg and 21 + /- 9 vs 23 + /- 9 ; P Strength increases correlated with the increase in initial claudication distance ( r = 0.64 ; P = .01 ) and with the decrease in VO(2 ) measured at the first stage of the treadmill test ( r = -0.52 ; P = .04 and r = -0.55 ; P = .03 ) . Adaptations following ST were similar to the ones observed after WT ; however , patients reported lower pain during ST than WT ( P ST improves functional limitation similarly to WT but it produces lower pain , suggesting that this type of exercise could be useful and should be considered in patients with IC", "The aim of the authors ' study was to investigate , in patients with one leg amputated , the influence of electrostimulation on the arterial circulation of the other lower limb and on the ability of a leg with deteriorated blood flow to perform work . The study encompassed 50 patients who were admitted to the rehabilitation center to obtain a leg prosthesis and learn to walk after amputation of 1 lower limb because of severe circulatory disturbance . The patients were r and omly divided into 2 groups . The first group contained 25 patients treated with a st and ard exercise program for patients with limb amputation ( control group , C ) . In this control group , according to the Fontaine 's classification of peripheral arterial occlusive disease ( PAOD ) , 15 patients were in stage I and 10 patients were in stage II . In the second group , the electro stimulated ( ES ) group , there were also 25 patients that had the same rehabilitation program , to which electrostimulation of the gastrocnemius muscle of the remaining leg was added . In this group , 14 patients were in stage I , 10 patients were in stage II , and 1 patient was in stage III of PAOD . For electrostimulation , biphasic charge-balanced asymmetrical current stimuli with a pulse duration of 0.25 ms were used . The electrostimulation program consisted of 2 hours of electrostimulation per day for 8 weeks . Each patient was examined at the start of the rehabilitation program ( examination I ) , at the end of the 8-week program ( examination II ) and at the end of a 1-year follow-up period ( examination III ) . The effects of the treatment were followed using clinical examination , determination of the ankle-brachial index ( ABI ) , and by measuring the partial oxygen pressure ( TcPO2 ) on the skin surface of the diseased leg at rest and during exercise . After 8 weeks of treatment , in 3 patients of the ES group , claudica tion disappeared , and they thus moved from clinical stage II to stage I. In the control group , there were no changes in the clinical stages of PAOD . At the end of the observation period , 6 patients in group C and 5 patients in the ES group registered a progression of PAOD . During the observation period , 3 patients in group C and 1 patient in the ES group had below-knee amputations of the remaining leg ( p Perfusion pressures and ABI of investigated legs were comparable between groups and did not change during treatment . After 1 year of obser vation , there was a trend to ABI decrease in both groups . The capability of the diseased leg for performing work increased significantly during treatment only in the ES group . During treatment , TcPO2 at rest on the dorsum of the foot increased nonsignificantly in the ES group but in group C a trend of decrease in its value was indicated . After 8 weeks of treatment , total and partial oxygen drop during exercise significantly decreased in the ES group ; whereas , in group C , there was no significant change . During the 1-year observation period , these effects of electrostimulation disappeared ; however , fewer amputations in the ES group favor the presumption that this could be a positive effect of electrostimulation . The results of the authors ' study showed that electrostimulation improved oxygen delivery to a leg with disturbed arterial circulation and increased its work load capacity . The changes are probably caused by improvement of", "Objective : To assess the effect of pain-free treadmill training on changes of plasma fibrinogen , haematocrit , lipid profile , and walking ability in patients with claudication . Design : R and omized control trial . Methods : Sixty-eight patients with peripheral obstructive arterial disease and intermittent claudication ( Fontaine stage II ) were r and omly assigned into the treadmill training ( repetitive intervals to onset of claudication pain , three times a week ) or a control group ( no change in physical activity ) over 3 months . Both groups performed treadmill test to assess pain-free walking time ( PFWT ) and maximal walking time ( MWT ) and had blood analyses [ for haematocrit , fibrinogen , triglycerides , and cholesterol : total , high-density lipoprotein ( HDL ) and low-density lipoprotein ( LDL ) ] done at baseline and after 6 and 12 weeks of the study . Results : Total and LDL cholesterol levels in the training group decreased ( p Significant ( p ( 19 % ) in the training group but changes of all these lipids were insignificant in the control group over the 3 months . Haematocrit and fibrinogen changes were insignificant in both groups . PFWT was prolonged by 109 % and MWT increased by 54 % in the training group ( p pain-free treadmill training parallels with progressive normalization of lipid profiles in patients with claudication", "OBJECTIVES To identify a stable biochemical marker of disease severity in patients with intermittent claudication and to use these findings to assess the effect of therapeutic exercise training . DESIGN Case-control study : prospect i ve r and omised-controlled trial of exercise training . MATERIAL S AND METHODS Plasma fibrinogen , serum amyloid A protein ( SAA ) , C-reactive protein ( CRP ) and urinary albumin-creatinine ratio ( ACR ) were measured in 67 claudicants and 15 controls . Twenty-two patients were r and omised to supervised exercise training and 17 r and omised to observation . Subjects were review ed at 3 , 6 and 12 months . RESULTS The median ( interquartile range ) baseline fibrinogen was 3.7 g/l ( 3.3 - 4.25 ) in claudicants and 3.5 g/l ( 2.9 - 3.95 ) in controls ( p = 0.045 ) ; CRP was 4.7 mg/l ( 2.2 - 9.0 ) and 2.1 mg/l ( 1.0 - 2.8 ) , respectively ( p SAA was 72 mg/l ( 35 - 132 ) and 30 mg/l ( 20 - 89 ) ( p = 0.0009 ) . Claudicants showed an increased urinary ACR following treadmill exercise ( Wilcoxon , p Exercise training reduced SAA at 6 months , CRP at 3 months and progressively attenuated the post-exercise increase in ACR . No similar changes were found in controls . CONCLUSIONS Repetitive low- grade inflammatory events in claudicants lead to elevation of serum acute-phase proteins . Exercise training is associated with symptomatic improvement and reduction inflammatory markers . The concern that exercise has adverse systemic effects therefore seems to be unjustified", "Because individuals with claudication pain secondary to peripheral arterial disease ( PAD ) are limited in both walking speed and duration , the benefits of walking exercise may be insufficient to yield a cardiovascular training effect . The objectives of this analysis were to determine whether polestriding exercise training , performed by persons with PAD , would improve exercise endurance , elicit a cardiovascular training benefit , and improve quality of life ( QoL ) . Persons ( n = 49 ) whose claudication pain limited their exercise capacity were r and omized into a 24-week polestriding training program ( n = 25 , 65.8 ± 7.1 years of age ) or a nonexercise attention control group ( n = 24 , 68.0 ± 8.6 years of age ) . Those assigned to the polestriding group trained 3 times weekly . Control group subjects came to the laboratory biweekly for ankle blood pressure measurements . A symptom-limited ramp treadmill test , ratings of perceived leg pain , and QoL data ( using the Short Form-36 ) were obtained at baseline and upon completion of training . After 24 weeks of polestriding training , subjects increased their exercise endurance from 10.3 ± 4.1 minute to 15.1 ± 4.5 minute . This was significantly greater than control group subjects whose exercise endurance declined ( from 11.2 ± 4.7 to 10.3 ± 4.7 minute ; P ( P ( P = .04 ) , rate pressure product ( P = .05 ) , oxygen uptake ( P = .016 ) , and perceived leg pain ( P = .02 ) and exercise time improved from the baseline symptom-limited treadmill test to the 6-month symptom-limited treadmill test in the polestriding group compared to the control group . The improvement in the physical component summary score of the Short Form-36 was also greater in the polestriding group ( P = .031 ) . Polestriding training significantly improved the clinical indicators of cardiovascular fitness and QoL , and decreased symptoms of claudication pain during exertion", "BACKGROUND Patients with intermittent lower limb claudication ( IC ) exhibit a prothrombotic diathesis that is acutely exacerbated by exercise . This may occur because of ischemia/reperfusion injury within the leg muscles during walking and may contribute to the increased risk of thrombotic vascular events in this group of patients . This r and omized study compared the effect of lower limb revascularization by percutaneous transluminal balloon angioplasty ( PTA ) , supervised exercise , and best medical therapy ( BMT ) alone on this prothrombotic state . METHODS Twenty-three patients ( 16 men and 7 women ; median age , 67 years ; range , 57 - 77 years ) with IC due to infrainguinal disease were r and omized to receive BMT alone ( n = 7 ) , BMT plus PTA ( n = 9 ) , or BMT plus supervised exercise ( n = 7 ) as part of the Health Technology Assessment -funded EXercise vs Angioplasty in Claudication Trial ( EXACT ) . Patients were assessed at baseline and at 3 and 6 months . Thrombin-antithrombin complex ( TAT ) was determined as a marker of thrombin generation , and plasminogen activator inhibitor ( PAI ) antigen was determined as a marker of fibrinolysis . Increased TAT indicates a procoagulant state , and increased PAI antigen indicates a hypofibrinolytic state . RESULTS At 6 months , subjects r and omized to BMT plus PTA demonstrated a significant improvement in ankle-brachial pressure index ( P = .013 ) and maximal walking distance ( P = .008 ) , a significant decline in resting thrombin generation ( median [ interquartile range ] TAT , 6.4 microg/L [ 2.7 - 13.5 microg/L ] to 1.5 microg/L [ 0.3 - 2.9 microg/L ] ; P = .038 ) , and an improvement in resting fibrinolysis ( median [ interquartile range ] PAI-1 , 10.0 ng/mL [ 1.0 - 20.5 ng/mL ] to 1.0 ng/mL [ 1.0 - 14.8 ng/mL ] ; P = .043 ) . There was no significant change in any of these parameters in patients r and omized to BMT plus supervised exercise or to BMT alone . CONCLUSIONS The addition of lower limb revascularization by PTA to BMT in patients with IC due to infra-inguinal disease results in a medium-term improvement in the resting procoagulant and hypofibrinolytic state . This may translate into a reduction in morbidity and mortality from thrombotic vascular events in this group of patients", "Arm cranking is a useful alternative exercise modality for improving walking performance in patients with intermittent claudication ; however , the mechanisms of such an improvement are poorly understood . The main aim of the present study was to investigate the effects of arm-crank exercise training on lower-limb O2 delivery in patients with intermittent claudication . A total of 57 patients with intermittent claudication ( age , 70+/-8 years ; mean+/-S.D. ) were r and omized to an arm-crank exercise group or a non-exercise control group . The exercise group trained twice weekly for 12 weeks . At baseline and 12 weeks , patients completed incremental tests to maximum exercise tolerance on both an arm-crank ergometer and a treadmill . Respiratory variables were measured breath-by-breath to determine peak VO2 ( O2 uptake ) and ventilatory threshold . Near-IR spectroscopy was used in the treadmill test to determine changes in calf muscle StO2 ( tissue O2 saturation ) . Patients also completed a square-wave treadmill-walking protocol to determine VO2 kinetics . A total of 51 patients completed the study . In the exercise group , higher maximum walking distances ( from 496+/-250 to 661+/-324 m ) and peak VO2 values ( from 17.2+/-2.7 to 18.2+/-3.4 ml.kg-1 of body mass.min-1 ) were recorded in the incremental treadmill test ( P time to minimum StO2 ( from 268+/-305 s to 410+/-366 s ) , a speeding of VO2 kinetics ( from 44.7+/-10.4 to 41.3+/-14.4 s ) and an increase in submaximal StO2 during treadmill walking ( P walking performance after arm-crank exercise training in patients with intermittent claudication is attributable , at least in part , to improved lower-limb O2 delivery", "OBJECTIVE To determine the effects of a 6-month exercise program on ambulatory function , free-living daily physical activity , peripheral circulation , and health-related quality of life ( QOL ) in disabled older patients with intermittent claudication . DESIGN Prospect i ve , r and omized controlled trial . SETTING University Medical ( Center and Veterans Affairs Medical Center , Baltimore , Maryl and . PARTICIPANTS Thirty-one of 61 patients with Fontaine stage II peripheral arterial occlusive disease ( PAOD ) were r and omized to exercise rehabilitation and 30 to usual-care control . Three patients from the exercise group and six patients from the control group dropped out , leaving 28 and 24 patients , respectively , completing the study in each group . INTERVENTION Six months of exercise rehabilitation . MEASUREMENTS Treadmill distance walked to onset of claudication and to maximal claudication , ambulatory function , peripheral circulation , perceived QOL , and daily physical activity . RESULTS Compliance with the exercise program was 73 % of the possible sessions . Exercise rehabilitation increased treadmill distance walked to onset of claudication by 134 % ( P maximal claudication by 77 % ( P walking economy by 12 % ( P = .003 ) , 6-minute walk distance by 12 % ( P maximal calf blood flow by 30 % ( P Changes in distance walked to maximal pain correlated with changes in walking economy ( r = -.50 , P = .013 ) and changes in maximal calf blood flow ( r = .38 , P = .047 ) . Exercise rehabilitation increased accelerometer-derived daily physical activity by 38 % ( P distance walked to maximal pain ( r = .45 , P = .020 ) . These improvements were significantly better than the changes in the control group ( P exercise rehabilitation in older PAOD patients are dependent on improvements in peripheral circulation and walking economy . Improvement in treadmill claudication distances in these patients translated into increased accelerometer-derived physical activity in the community , which enabled the patients to become more functionally independent", "BACKGROUND Exercise training is recommended as the first-line therapy for intermittent claudication patients . However , the effects of exercise therapy on cardiovascular function of these patients have been poorly studied . The aim of this study is to compare the effects of walking and strength training on cardiovascular responses assessed at rest and during exercise in patients with intermittent claudication . PATIENTS AND METHODS Thirty-four patients with stable symptoms of intermittent claudication were r and omized into two groups : strength training ( ST ) consisting of eight exercises , three sets of 10 repetitions , intensity of 11 - 13 on 15- grade Borg scale , 2-min interval between sets ; and walking training ( WT ) consisting of walking on a treadmill , 15 bouts of 2-min , intensity of 11 - 13 on 15- grade Borg scale , with a 2-min interval between bouts . Before and after 12 weeks , blood pressure , heart rate and rate pressure product were measured at rest and during a progressive treadmill test until maximal claudication pain . RESULTS Fifteen patients in each group completed the training program . After the training programs , resting systolic blood pressure ( ST:-6 ± 13 mmHg and WT:-3 ± 18 mmHg , P = .04 ) , heart rate ( ST : -6 ± 10 bpm and WT:-2 ± 9 bpm , P = .03 ) , and rate pressure product ( ST:-1485 ± 1442 mmHgbpm and WT:- 605 ± 2145 mmHgbpm , P = .01 ) decreased significantly and similarly in both groups . Submaximal systolic blood pressure ( ST : -14 ± 23 mmHg and WT:-6 ± 23 mmHg , P = .02 ) , and rate pressure product ( ST:-1579 ± 3444 mmHgbpm and WT : -1264 ± 3005 mmHgbpm , P = .04 ) decreased significantly and similarly in both groups . There were no changes in submaximal heart rate after ST and WT . Maximal systolic blood pressure , heart rate , and rate pressure product did not change in either group , although maximal exercise time increased similarly in the ST and WT groups ( + 31 ± 19 % , and + 31 ± 32 % , respectively , P . CONCLUSIONS Strength and walking trainings promoted similar increases in walking capacity and decreases in resting and submaximal exercise cardiovascular load", "An intensive 4-week vascular training ( patients with PAOD IIb ) leads to an effective amelioration of painfree walking distance ( + 120 % ) . Additive i.v . Pentoxifylline was not more effective ( + 105 % ) whereas PGE1 showed a remarkable increase ( + 605 % ) . After one year the results in all groups diminished : training group : + 30 % , Pentoxifylline group : + 30 % , PGE1 group : + 149 %", "OBJECTIVES To investigate the effects of a 24-week program of upper- and lower-limb aerobic exercise training on walking performance in patients with symptomatic peripheral arterial disease ( PAD ) and to study the mechanisms that could influence symptomatic improvement . METHODS After approval from the North Sheffield Local Research Ethics Committee , 104 patients ( median age , 69 years ; range , 50 to 85 years ) with stable PAD were r and omized into an upper- or lower-limb aerobic exercise training group ( UL-Ex or LL-Ex ) , or to a nonexercise training control group . Training was performed twice weekly for 24 weeks at equivalent relative exercise intensities . An incremental arm- and leg-crank test ( ACT and LCT ) to maximum exercise tolerance was performed before and at 6 , 12 , 18 , and 24 weeks of the intervention to determine peak oxygen consumption ( VO(2 ) ) . Walking performance , defined as the claudicating distance ( CD ) and maximum walking distance ( MWD ) achieved before intolerable claudication pain , was assessed at the same time points by using a shuttle-walk protocol . Peak blood lactate concentration , Borg ratings of perceived exertion ( RPE ) and pain category ratio ( CR-10 ) were recorded during all assessment s. RESULTS CD and MWD increased over time ( P CD had improved by 51 % and 57 % , and MWD had improved by 29 % and 31 % ( all P peak heart rate at MWD in the UL-Ex group ( 109 + /- 4 vs 115 + /- 4 beats/min ; P amount of pain experienced in both groups ( P cardiovascular stress and an increased intensity of claudication pain before test termination after training . Patients assigned to exercise training also showed an increase in LCT peak VO2 at the 24-week time point in relation to baseline ( P ACT peak VO2 was only improved in the UL-Ex group ( P upper-limb aerobic exercise training in patients with PAD . Furthermore , that both arm- and leg-crank training could be useful exercise training modalities for improving cardiovascular function , walking performance , and exercise pain tolerance in patients with symptomatic PAD", "The efficacy of physical training alone or combined with antiplatelet thera py ( dipyridamole and aspirin ) was studied in 30 patients with stage II peripheral arterial occlusive disease ( PAOD ) . Patients were r and omly allocated to one of the following groups : Group A— dipyridamole 75 mg three times daily and aspirin 330 mg once daily : Group B— physical exercise ; Group C — physical exercise and dipyridamole 75 mg three time daily and aspirin 330 mg once daily . After six months ' treatment the pain-free walking time ( PFWT ) and the max imum walking time ( MWT ) improved significantly ( p PFWT lengthened by 35 % ( from 101.00 ± 34.56 to 137.32 ± 40.50 s ) and the MWT by 38 % ( from 150.34 ± 55.60 to 207.26 ± 60.67 s ) ; in group B the PFWT lengthened by 90 % ( from 90.65 ± 40.54 to 171.45 ± 55.60 s ) and the MWT by 86 % ( from 145.39 ± 60.50 to 270.63 ± 63.61 s ) . When physical exer cise was associated with drugs as in group C , the PFWT lengthened by 120 % ( from 89.51 ± 43.89 to 196.72 ±51.73 s ) and the MWT by 105 % ( from 160.43 ± 59.84 to 329.05 ± 63.96 s ) . No significant variations were observed at any stage of the study in the ankle/arm pressure ratio at rest and after st and ard treadmill exercise , in the plethysmographic rest and peak flows , or in the trans cutaneous oxygen pressure in basal conditions and in its half recovery time after an induced ischemia . The results confirm the benefits of regular exercise in stage II PAOD pa tients but suggest they may be enhanced by antiplatelet therapy ", "The purpose of this study was to investigate the effects of a progressive resistance training program on myosin heavy chain isoform expression , fiber type , and capillarization in patients with symptomatic peripheral arterial disease . Patients were r and omized to either a training group ( n = 11 , mean + /- SD , 70 + /- 6 years , 4 men , 7 women ) or a control group ( n = 9 , 66 + /- 6 years , 5 men , 4 women ) . The training sessions were completed 3 times/week , using 2 sets of various exercises , each performed for 8 - 15 repetitions . Muscle biopsies were obtained before and after 24 weeks from the medial gastrocnemius . Following the 24-week training program , the training group had significantly decreased the percentage of myosin heavy chain type IIB . The proportion of type IIB/AB fibers as measured by using myosin adenosine triphosphatase histochemistry decreased significantly in the training group . There were significant increases in type I and type II fiber areas , and capillary density also increased significantly in the training group . There were significant increases in 10 repetition maximum leg press and calf press strengths in the trained subjects . There were no significant changes in any of the measurements in the control group . It is concluded that progressive resistance training results in significant increases in muscle strength and alters skeletal muscle composition of subjects with peripheral arterial disease", "Objectives To assess the effect of pain-free treadmill training on red blood cell deformability and walking distance in patients with claudication . Design R and omized-controlled trial of exercise training . Setting Patients were recruited from the primary care , vascular outpatient clinic . Patients A total of 60 patients with peripheral arterial occlusive disease ( stage II according to Leriche-Fontaine ) were r and omized into the treadmill program or a control group . Fifty-five patients completed the study ( 27 in the exercising group and 28 in the control group ) . Interventions Patients in the exercising group were walking on the treadmill 3 times a week for 3 months . Each session consisted of 1 hour repetitive walking [ performed to 85 % of the pain-free walking time ( PFWT ) ] was supervised by a qualified physiotherapist . Main Outcome Measurements Changes in erythrocyte deformability and treadmill walking performance ( PFWT , maximal walking time ) were assessed in both groups before the study and after 3 months . Results After 3 months of treadmill training , red blood cell deformability in the exercising group significantly increased ( P the erythrocyte deformability in the control group . PFWT was prolonged by 102 % from 191±34 to 386±60 seconds ( P ) , and maximal walking time increased by 49 % from 438±62 to 656±79 seconds ( P 3 months of pain-free treadmill training is associated with a significant increase in red cell deformability in patients with claudication", "Twenty-three patients with intermittent claudication were su bmi tted to physical training during 4 - 6 months . Eleven other patients with intermittent claudication served as a control group and were given placebo tablets during the same period . The aim of the investigation was to study the influence of physical training on the blood flow conditions in the calf . The effect of treatment on walking tolerance , on calf blood flow , blood flow resistance , and systolic blood pressure graident between the systemic circulation and the vascular bed in the calf was studied . Half a year after the end of the treatment period the patients were reexamined . The walking tolerance increased in both groups but more in the trained group . The increase in walking tolerance even in the control group was caused by the fact that the control group began to train to some extent . In neither group the maximal calf blood flow changed significantly compared with the pretreatment values . The maximal blood flow showed an increasing trend in the training group after a period fo 4 months compared with the control goupr ( 2p greater than 0.10 ) . The blood flow resistance at maximal dilatation did not change significantly as compared with the initial values in any of the groups , but there was a significant difference ( 2p greater than 0.05 ) between the two groups with a decrease in the training group after 4 months . The changes in maximal calf blood flow and the changes in blood flow resistance at maximal dilatation were not related to the changes in walking tolerance . Half a year after the treatment period the walking tolerance had not decreased and there was no difference between the two groups . The maximal calf blood flow , the blood flow resistance , and the systolic pressure gradient were unchanged in comparison with the pretreatment values and there were no statistically significant differences between the two groups . The small changes in blood flow conditions observed after physical training can not be the only factor explaining the well known improvement in walking tolerance . However , training may cause a redistribution of the blood flow in the working muscle", "PURPOSE We have previously shown that a program of upper limb exercise training can induce significant improvements in walking distance in patients with claudication . This study assessed whether upper limb exercise avoids the systemic inflammatory responses associated with lower limb exercise and also whether the inflammatory response to acute lower limb exertion is modified by a program of supervised exercise training . METHODS Fifty-two patients with stable intermittent claudication were r and omized into two groups who underwent 6 weeks of supervised upper ( n = 26 ) or lower ( n = 26 ) limb cardiorespiratory exercise training . A parallel control group ( n = 15 ) was provided with lifestyle advice only . Neutrophil activation markers ( CD11b and CD66b ) and plasma levels of von Willebr and factor ( marker of endothelial damage ) in response to an acute bout of sustained upper and lower limb exercise were assessed before and after the period of training . Plasma levels of soluble E-selectin ( marker of endothelial activation ) were also determined before and after the training period . RESULTS An acute bout of sustained lower limb exercise significantly increased the intensity of CD11b and CD66b expression by peripheral blood neutrophils in all groups , whereas upper limb exercise had no effect . Resting neutrophil expression of CD11b and CD66b and circulating von Willebr and factor levels were unaffected by the training program , as were the inflammatory responses to an acute bout of sustained upper and lower limb muscular work , despite the fact that both training programs significantly increased walking distances . CONCLUSIONS These findings indicate that upper limb exercise training programs may offer certain advantages over currently prescribed lower limb programs . Our results show that exercising nonischemic muscles in a way that promotes improved cardiorespiratory function and walking capacity can avoid the potentially deleterious systemic inflammatory responses associated with lower limb exertion in patients with stable intermittent claudication", "In patients with intermittent claudication , exercise is associated with a marked increase in oxidative stress , likely responsible for systemic endothelial perturbation . In 31 claudicant patients , we assessed the effect of vitamin C administration on the acute changes induced by maximal and submaximal exercise in endothelium-dependent , flow-mediated dilation ( FMD ) , and in plasma levels of thiobarbituric acid-reactive substances ( TBARS ) and soluble intercellular adhesion molecule-1 ( sICAM-1 ) . In 16 claudicants , maximal exercise reduced FMD ( from 8.5+/-0.9 to 3.7+/-0.8 % , P plasma levels of TBARS ( from 1.93+/-0.06 to 2.22+/-0.1 nmol/ml , P sICAM-1 ( from 282+/-17 to 323+/-19 ng/ml , P vitamin C , exercise-induced changes in FMD and biochemistry were abolished . This beneficial effect was not observed in the eight patients r and omized to saline . In 15 patients , who walked until the onset of claudication pain ( submaximal exercise ) , and in ten control subjects , who performed maximal exercise , no changes were observed with exercise . Thus , in claudicants , vitamin C prevents the acute , systemic impairment in endothelial function induced by maximal exercise . This finding provides a rationale for trials investigating antioxidant therapy and cardiovascular risk in patients with intermittent claudication", "Abstract The efficacy of treadmill walking training to improve pain-free ( PFWD ) and maximal ( MWD ) walking distance in patients with claudication is well documented . The effects of aerobic arm-ergometry to improve PFWD and MWD compared to treadmill walking or usual care are not known . Forty-one participants ( 29 male , 12 female , mean age 67.7 years , 92.7 % smoking history , 36.6 % with diabetes ) with lifestyle-limiting claudication were r and omized to 12 weeks of 3 hours/week of supervised exercise training using either arm-ergometry , treadmill walking , or a combination , versus control . PFWD and MWD were assessed before and after training , and after 12 weeks of follow-up . The 12-week MWD increased significantly in the arm-ergometry ( + 53 % ) , treadmill ( + 69 % ) , and combination ( + 68 % ) groups ( p 24-week MWD was maintained in the arm-ergometry ( p = 0.009 ) and treadmill ( p = 0.019 ) groups , whereas the combination group declined ( p = 0.751 ) versus control . The 12-week PFWD increased significantly in the arm-ergometry group ( + 82 % ; p = 0.025 versus control ) . Change in PFWD in treadmill ( + 54 % ; p = 0.196 versus control ) and combination ( + 60 % ; p = 0.107 versus control ) groups did not reach statistical significance . PFWD improvement was maintained in the arm-ergometry group after a 12-week follow-up ( + 123 % ; p = 0.011 versus control ) . In conclusion , these pilot data demonstrate for the first time that dynamic arm exercise training can improve walking capability in people with peripheral arterial disease (PAD)-induced claudication compared to participants receiving usual care and that improvement was not different from that seen with treadmill walking exercise training . Dynamic arm exercise may be a therapeutic exercise option for patients with PAD", "PURPOSE To compare treadmill and shuttle walk tests for assessing functional capacity in patients with intermittent claudication , with respect to test-retest reliability , cardiovascular responses , and patient preferences . METHODS Patients with stable intermittent claudication ( N = 55 , ages 52 - 85 yr , median age 68 yr ) were recruited from the Sheffield Vascular Institute at the Northern General Hospital , Sheffield , UK . Each patient performed an incremental shuttle walk test , a constant-pace shuttle walk test , and a st and ardized treadmill test ( 3.2 km x h(-1 ) , 12 % gradient ) , each on three occasions . The incremental shuttle walk began at 3 km x h(-1 ) and increased by 0.5 km x h(-1 ) every minute , whereas the constant-pace shuttle walk was performed at the fixed pace of 4 km x h(-1 ) . Claudication distance ( CD ) , maximum walking distance ( MWD ) , heart rate ( HR ) , and blood pressure were assessed in each testing session . The patients also completed a test preference question naire . RESULTS CD and MWD for both shuttle walks were greater than the corresponding walking distances achieved in the treadmill test ( P Average coefficients of variation for repeated incremental shuttle walk , constant-pace shuttle walk , and treadmill tests were 15.9 % , 21.1 % , and 18.7 % , respectively , for MWD , corresponding to average intraclass correlation coefficients of 0.87 , 0.82 , and 0.87 . Treadmill walking evoked greater increases in HR and blood pressure ( P preference for it ( 24 vs 43 % for shuttle walking ) . CONCLUSION These findings indicated that shuttle walk testing exhibits similar test-retest reliability as treadmill testing , but that it evoked a lower level of cardiovascular stress and is preferred to treadmill testing by a large proportion of patients", "OBJECTIVES Despite limited scientific evidence for the effectiveness of invasive treatment for intermittent claudication ( IC ) , revascularisation procedures for IC are increasingly often performed in Sweden . This r and omised controlled trial compares the outcome after 2 years of primary invasive ( INV ) versus primary non-invasive ( NON ) treatment strategies in unselected IC patients . MATERIAL S/ METHODS Based on arterial duplex and clinical examination , IC patients were r and omised to INV ( endovascular and /or surgical , n = 100 ) or NON ( n = 101 ) . NON patients could request invasive treatment if they deteriorated during follow-up . Primary outcome was maximal walking performance ( MWP ) on grade d treadmill test at 2 years and secondary outcomes included health-related quality of life ( HRQL ) , assessed with Short Form ( 36 ) Health Survey ( SF-36 ) . RESULTS MWP was not significantly ( p = 0.104 ) improved in the INV versus the NON group . Two SF-36 physical subscales , Bodily Pain ( p Role Physical ( p MWP , the HRQL improvements associated with invasive treatment tentatively suggest secondary benefits of this regimen . On the other h and , a primary non-invasive treatment strategy seems to be accepted by most IC patients", " PURPOSE To determine whether a percutaneous vascular intervention ( PVI ) combined with supplemental supervised exercise therapy ( SET ) is more effective than a PVI alone in improving walking ability in patients with symptomatic peripheral arterial disease ( PAD ) . MATERIAL S AND METHODS In this prospect i ve r and omized trial , patients with PAD treated with a PVI were eligible . Exclusion criteria were major amputation or tissue loss , comorbidity preventing physical activity , insufficient knowledge of the Dutch language , no insurance for SET , and prior participation in a SET program . All patients received a PVI and subsequently were r and omly assigned to either the PVI alone group ( n = 35 ) or the PVI + SET group ( n = 35 ) . The primary outcome parameter was the absolute claudication distance ( ACD ) . This trial was registered at Clinical trials.gov , NCT00497445 . RESULTS The study included 70 patients , most of whom were treated for an aortoiliac lesion . The mean difference in ACD at 6 months of follow-up was 271.3 m ( 95 % confidence interval [ CI ] 64.0 - 478.6 , P = .011 ) in favor of additional SET . In the PVI alone group , 1 ( 3.7 % ) patient finished the complete treadmill test compared with 11 ( 32.4 % ) patients in the PVI + SET group ( P = .005 ) . Physical health-related quality -of-life score was 44.1 ± 7.8 in the PVI alone group compared with 41.9 ± 9.5 in the PVI + SET group , which was a nonsignificant difference ( P = .34 ) . CONCLUSIONS SET following a PVI is more effective in increasing walking distance compared with a PVI alone . These data indicate that SET is a useful adjunct to a PVI for the treatment of PAD", "OBJECTIVE To determine the effects of 12-week exercise programme on ambulatory function , free-living daily physical activity and health-related quality of life in disabled older patients with intermittent claudication . DESIGN Prospect i ve , r and omized controlled trial . SETTING University Medical Center and Veterans Affairs Medical Center , Taipei , Taiwan . SUBJECTS Thirty-two of 64 patients with Fontaine stage II peripheral arterial occlusive disease ( PAOD ) were r and omized to exercise training and 32 to usual care control . Five patients from the exercise group and six patients from the control group dropped out , leaving 27 and 26 patients , respectively , completing the study in each group . INTERVENTIONS Twelve weeks of treadmill exercise training . MAIN OUTCOME MEASURES Treadmill walking time to onset of claudication pain and to maximal claudication pain , 6-min walk distance , self-reported ambulatory ability and perceived health-related quality of life ( QOL ) . RESULTS Compliance of exercise programme was 83 % of the possible sessions . Exercise training increased treadmill walking time to onset of claudication pain by 88 % ( P time to maximal pain by 70 % ( P 6-min walk distance by 21 % ( P Perception of health-related QOL improved from 12 % to 178 % in the exercise group . These improvements were significantly better than the changes in the control group ( P claudication following 12-week exercise training in elderly PAOD patients were observed . Increase in treadmill walking time to maximal claudication pain in these patients translated into the improvement of perceived physical health , which enabled the patients to become more functionally independent", "OBJECTIVES To compare the correlation and practicability of single-stage vs. grade d treadmill protocol s in the assessment of the absolute claudication distance ( ACD ) . DESIGN R and omized open study . MATERIAL AND METHODS In 52 patients with peripheral arterial occlusive disease , the ACD on treadmill at 3 km/h and 12 % grade ( constant-load test = C-test ) ranged form 50 to 400 m. The C-test and the grade d-exercise test ( walking on the treadmill at 3 km/h and 0 % gradient for 3 min , with subsequent increase in gradient of 3.5 % every 3 min = G-test ) were carried out at r and om on the same day under st and ardized conditions . RESULTS The ACD was higher in the G-test than in the C-test ( 360.4 + /- 208.8 m vs. 166.5 + /- 93.6 m ; p coefficients of variation were very similar ( 57.9 % and 56.2 % , respectively ) . In the subgroup of patients with an ACD of between 100 m and 150 m , a large difference was found both for the coefficient of variation ( 58.6 % G-test , 9.6 % C-test ) and for the st and ard deviation ( 339.8 + /- 199.0 m and 133.1 + /- 12.8 m , respectively ) . CONCLUSIONS For the assessment of the ACD in patients with severe claudication the C-test would seem to be more suitable than the G-test", "OBJECTIVE to compare the effectiveness of invasive therapy , supervised physical training and no treatment in terms of health-related quality of life ( HRQL ) in patients with intermittent claudication ( IC ) . DESIGN a prospect i ve , r and omised , controlled study . MATERIAL S a total of 253 unselected patients with stable IC were sequentially r and omised into 3 balanced treatment groups . At 1 year follow-up data from a battery of generic and disease specific HRQL question naires , and global indices of quality of life and physical condition were available in 171 patients . RESULTS compared with a non-diseased reference group , claudicants were substantially limited in daily physical functioning , but little affected regarding emotional , cognitive and social functioning , or well-being . Invasive therapy yielded significantly greater improvements in some aspects of physical functioning and walk-related symptoms than training . Training was not superior to invasive therapy on any HRQL dimension and superior to no treatment on only one dimension . Treatment effects , however , were generally small-to-moderate and levels of physical dysfunction in all groups remained higher than reference values . CONCLUSIONS invasive therapy is more effective than supervised training in alleviating illness-specific symptoms and improving certain aspects of physical functioning - the primary HRQL domains impacted on by IC and the principal goals of its treatment . However , since treatment effect sizes were at most moderate and given that untreated claudicants reported at most small deterioration in HRQL , the level of evidence supporting invasive therapy is modest", "OBJECTIVE Prevalence of peripheral arterial disease is equal in men and women . However , women seem to suffer more from the burden of disease . Current studies on gender-related outcomes following supervised exercise therapy ( SET ) for intermittent claudication ( IC ) yield conflicting results . METHODS A follow-up analysis was performed on data from the 2010 Exercise Therapy in Peripheral Arterial Disease ( EXITPAD ) study , a multicenter r and omized controlled trial including IC patients receiving SET or a walking advice . The SET program was supervised by physiotherapists and included interval-based treadmill walking approximating maximal pain combined with activities such as cycling and rowing . Patients usually started with three 30-minute sessions a week . Training frequency was adapted during the following year on the basis of individual needs . The primary outcome was gender differences regarding the change in absolute claudication distance ( ACD ) after SET . ACD was defined as the number of meters that a patient had covered just before he or she was forced to stop walking because of intolerable pain . Secondary outcomes were gender differences in change of functional walking distance , quality of life , and walking (dis)ability after SET . Walking distances were obtained by st and ardized treadmill testing according to the Gardner-Skinner protocol . Quality of life was measured by the 36-Item Short Form Health Survey , and walking (dis)ability was determined by the Walking Impairment Question naire ( WIQ ) . Measurements were performed at baseline and after 3 , 6 , 9 , and 12 months . Only patients who met the 12-month follow-up measure were included in the analysis . RESULTS A total of 113 men and 56 women were available for analysis . At baseline , groups were similar in terms of clinical characteristics and ACD walking distances ( men , 250 meters ; women , 270 meters ; P = .45 ) . ACD improved for both sexes . However , ACD increase was significantly lower for women than for men during the first 3 months of SET ( Δ 280 meters for men vs Δ 220 meters for women ; P = .04 ) . Moreover , absolute walking distance was significantly shorter for women compared with men after 1 year ( 565 meters vs 660 meters ; P = .032 ) . Women also reported less on several WIQ subdomains , although total WIQ score was similar ( 0.69 for men vs 0.61 for women ; P = .592 ) . No differences in quality of life after SET were observed . CONCLUSIONS Women with IC benefit less during the first 3 months of SET and have lower absolute walking distances after 12 months of follow-up compared with men . More research is needed to determine whether gender-based IC treatment strategies are required", "BACKGROUND Uncertainty exists on whether there is adjuvant benefit of percutaneous transluminal angioplasty ( PTA ) over supervised exercise and best medical therapy in the treatment of intermittent claudication . METHODS Patients with symptoms of stable mild to moderate intermittent claudication ( MIMIC ) were r and omised in two multi-centre trials , for femoropopliteal and aortoiliac arterial disease , to receive either PTA or no PTA against a background of supervised exercise and best medical therapy and followed up for 24 months . Initial claudication distance ( ICD ) and absolute walking distance ( AWD ) on treadmill were compared between r and omised groups adjusting for the corresponding measure at baseline . Secondary outcomes included ankle-brachial pressure index ( ABPI ) and quality of life . FINDINGS A total of 93 patients were r and omised into the femoropopliteal trial ( 48 into PTA ) and 34 into the aortoiliac trial ( 19 to PTA ) . The mean ( st and ard deviation , SD ) age was 66(9 ) years for the femoropopliteal trial ( 63 % male ) and 63(9 ) for the aortoiliac trial ( 65 % male ) . At 24 months , there were significant improvements in both AWD and ICD in the PTA groups for both trials . The adjusted AWD was 38 % greater in the PTA group for the femoropopliteal trial ( 95 % ; CI 1 - 90 ) ( p=0.04 ) and 78 % greater in the PTA group for the aortoiliac trial ( 95 % ; CI 0 - 216 ) ( p=0.05 ) . Further benefits were demonstrated for ABPI but not for quality of life . INTERPRETATION PTA confers adjuvant benefit over supervised exercise and best medical therapy in terms of walking distances and ABPI 24 months after PTA in patients with stable mild to moderate intermittent claudication", "Supervised walking exercise is an effective treatment to improve walking ability of patients with peripheral artery disease ( PAD ) , but few exercise programs in community setting s have been effective . The aim of this study was to determine the efficacy of a community-based walking exercise program with training , monitoring and coaching ( TMC ) components to improve exercise performance and patient-reported outcomes in PAD patients . This was a r and omized , controlled trial including PAD patients ( n=25 ) who previously received peripheral endovascular therapy or presented with stable claudication . Patients r and omized to the intervention group received a comprehensive community-based walking exercise program with elements of TMC over 14 weeks . Patients in the control group did not receive treatment beyond st and ard advice to walk . The primary outcome in the intent-to-treat ( ITT ) analyses was peak walking time ( PWT ) on a grade d treadmill . Secondary outcomes included claudication onset time ( COT ) and patient-reported outcomes assessed via the Walking Impairment Question naire ( WIQ ) . Intervention group patients ( n=10 ) did not significantly improve PWT when compared with the control group patients ( n=10 ) ( mean±st and ard error : + 2.1±0.7 versus 0.0±0.7 min , p=0.052 ) . Changes in COT and WIQ scores were greater for intervention patients compared with control patients ( COT : + 1.6±0.8 versus −0.6±0.7 min , p=0.045 ; WIQ : + 18.3±4.2 versus −4.6±4.2 % , p=0.001 ) . This pilot using a walking program with TMC and an ITT analysis did not improve the primary outcome in PAD patients . Other walking performance and patient self-reported outcomes were improved following exercise in community setting s. Further study is needed to determine whether this intervention improves outcomes in a trial employing a larger sample size", "The mechanisms by which exercise training improves intermittent claudication remain unclear . In this article , the effects of local and systemic physiological factors on improved exercise tolerance after a supervised exercise program in claudicants are investigated . A total of 60 patients were r and omized to 3 months of supervised exercise followed by 3 months of unsupervised exercise , or to exercise advice alone ( control ) . Supervised exercise increased both pain-free and maximal walking distances . Heart rate during submaximal exercise and resting mean arterial pressure were lower after supervised exercise at 6 months . Serum lactate at maximum claudication increased significantly after 3 months in the supervised exercise group but this change had resolved by 6 months . Symptomatic improvement was accompanied by modest reductions in mean arterial pressure and submaximal heart rate on exercise . Increased serum lactate at maximum claudication subsequently declined despite continued improvement in walking distance , suggesting local adaptations to improve efficiency of muscle oxygen delivery and /or utilization", "The clinical significance of drugs improving red cell deformability is not confirmed . We established the effect of physical training alone and combined with flunarizine on intermittent claudication . Twelve patients aged 48 - 73 years were included in the study . Pain-free walking distance on treadmill , ankle/arm pressure ratio and transcutaneous oxygen tension were measured . Walking distance increased significantly ( p less than 0.05 ) by 130 % from 75 m to 173 m during the first year when the patients were on programmed physical training . Ankle/arm pressure ratio also increased significantly ( p less than 0.05 ) from 0.46 to 0.55 during this period . The increase in walking distance ceased when the programmed physical training was discontinued for 6 months . During the following double-blind , cross-over medication period the patients were given flunarizine 5 mg b.i.d . and placebos in r and omized order for 3 months each . They also continued the same programmed physical training as during the first year . Walking distance increased , albeit not significantly , with time to 392 m after the second medication period . There was no difference , however , between flunarizine and placebo . Ankle/arm pressure ratio was of the same magnitude as at the beginning of the trial . Oxygen tension measurements did not give consistent results . We conclude that programmed physical training increased walking distance as a function of time . Flunarizine had no effect on the performance of patients with intermittent claudication", "OBJECTIVE The aim of this study was to identify whether revascularization by percutaneous transluminal angioplasty ( PTA ) for patients with intermittent claudication improved measures of functional performance including balance . METHODS A prospect i ve observational study was performed at a single tertiary vascular center . Patients with symptomatic intermittent claudication ( Rutherford grade s 1 - 3 ) were recruited to the study . Participants were assessed at baseline ( pre-PTA ) and then 3 , 6 , and 12 months post-PTA for markers of ( 1 ) lower limb ischemia ( treadmill walking distances and ankle-brachial pressure index ) , ( 2 ) physical function ( 6-minute walk , Timed Up and Go , and chair st and time ) , ( 3 ) balance impairment using computerized dynamic posturography with the Sensory Organization Test , and ( 4 ) quality of life ( VascuQoL and Short Form Health Survey [ SF-36 ] ) . RESULTS Forty-three participants underwent PTA . Over 12 months , a significant improvement was demonstrated in initial ( P = .04 ) and maximum treadmill walking distance ( P = .019 ) . Physical functional ability improved across all outcome measures ( P disease-specific quality of life ( P improvement in balance was demonstrated by the Sensory Organization Test ( P = .24 ) . CONCLUSIONS Balance impairment is common in claudicants and does not improve with revascularization . Further research regarding effective treatment of balance impairment is required in this specific group of patients", "Objective . Current guidelines for treatment of intermittent claudication ( IC ) do not include a specific recommendation for the intensity of exercise therapy . Thus , the purpose of this study was to determine the relative effectiveness of high versus low intensity exercise for patients with IC , and further to study the effect of such training on blood flow to the legs during exercise . Design . The effect of eight weeks of supervised endurance training was examined in 16 patients with IC . The patients were r and omly assigned to training at intensities corresponding to either 60 % or 80 % of their peak oxygen consumption ( VO2peak ) , respectively . Results . VO2peak and time to exhaustion increased significantly ( 9 % and 16 % , respectively ) more in the high intensity group ( p Blood flow to the legs did not change after training in any of the groups . Conclusion . High intensity training gave larger improvements in VO2peak and time to exhaustion than low intensity training . As blood flow did not change after the exercise program , it is likely that the observed different increase of VO2peak was due to changed mitochondrial oxidative capacity and /or skeletal muscle diffusive capacity", "Earlier investigations had shown that an intensive physiotherapy program with 30 treatments in 6 weeks was the most rational therapy for intermittent claudication , but the question whether the therapeutic success could be improved by the addition of \" vasoactive \" substances remained open . For this reason , bencyclane was added to the basic physiotherapy in a double blind trial involving 109 ambulant patients . 91 or these were evaluated . The treatment group ( n = 45 ) showed a greater increase in walking distance of 21.7 % compared with the placebo group ( n = 46 ) . Also in the evaluation of the therapeutic success rate , the treatment group showed better results ( 84.4 % ) than the placebo group ( 71.7 % ) . From this it can be concluded that the basic physiotherapy can be effectively supported with bencyclane", "This study reports the initial evaluation of treatment efficiency in 75 patients with intermittent claudication who were r and omized to three treatment groups : 1 ) reconstructive surgery , 2 ) recon structive surgery with subsequent physical training , and 3 ) physical training alone . Before treatment , there were no statistically significant differences between the groups in age , sex , smoking habits , symptom duration of claudication , ankle-arm blood pressure quotient ( ankle-index ) , maximal plethysmographic calf blood flow , symptom-free and maximal walking distance , the history of other atherosclerotic manifestations or in the medical treatment . The walking performance was improved in all three groups at follow-up 13 ± 0.5 months after r and omization . Surgery was most effective , but the addition of training to surgery improved the symptom-free walking distance even further . In pooled observations of the three groups , age , symptom duration , and a history of myocardial ischemic disease correlated negatively with walking performance after treatment . In the operated group , the duration of claudication and a history of myocardial ischemic disease correlated negatively with the walking performance . This was not the case when patients were censored if limited by other symptoms than intermittent claudication after treatment . In the trained group , the duration of claudication correlated negatively to symptom-free and maximal walking distance . Ankle-index and maximal plethysmographic calf blood flow after treatment and the change of these variables with treatment correlated positively with both symptom-free and maximal walking distance when results were pooled for all patients . Although this mainly was a consequence of the improved blood flow after surgery , the change of maximal plethysmographic calf blood flow also correlated with symptom-free but not with maximal walking distance in the trained group . The results demonstrate that , compared with physical training alone , operation alone or in combination with subsequent training are superior treatment modalities in patients with intermittent claudication", "INTRODUCTION Treatment of intermittent claudication ( IC ) due to peripheral arterial disease ( PAD ) is aim ed at improving walking distance and includes secondary prevention of cardiovascular disease . Both supervised exercise therapy ( SET ) and percutaneous transluminal angioplasty ( PTA ) have proven to be effective in increasing maximum and pain-free walking distance in IC . However , the optimal treatment strategy in patients with IC due to iliac artery stenosis or occlusion remains unclear . OBJECTIVE To compare the ( cost- ) effectiveness of initial PTA versus initial SET in patients with disabling IC due to an iliac artery obstruction . DESIGN In a multicentre r and omised controlled trial 400 consecutive patients with IC will be r and omly assigned to PTA ( with additional stent placement on indication ) or SET . Primary outcomes are maximum walking distance and health-related quality of life measured using the disease-specific VascuQol instrument after 1 year . Secondary outcomes are pain-free walking distance , functional status , generic quality of life , complications related to each of the interventions , additional interventions , treatment failures and costs ( cost-effectiveness and cost-utility ) after 1 year . CONCLUSION AND IMPLICATION S Based on the results of this proposed large study well-founded adjustments of existing guidelines on the treatment of iliac artery occlusive disease can be implemented ( Clinical Trials.gov NCT01385774 ; Nederl and s Trial Register NTR2776 )", "OBJECTIVE The initial treatment for intermittent claudication is supervised exercise therapy ( SET ) . Owing to limited capacity and patient transports costs of clinic-based SET , a concept of SET provided by local physiotherapists was developed . We hypothesized that provision of daily feedback with an accelerometer in addition to SET would further increase walking distance . METHODS This multicenter r and omized trial was set in vascular surgery outpatient clinics and included 304 patients with intermittent claudication . Patients were r and omized to exercise therapy in the form of \" go home and walk \" advice ( WA ) , SET , or SET with feedback . Local physiotherapists provided SET . The primary outcome measure was the change in absolute claudication distance . Secondary outcomes were the change in functional claudication distance and results on the Walking Impairment Question naire ( WIQ ) and Short-Form 36 ( SF-36 ) Health Survey after 12 months . RESULTS In 11 centers , 102 , 109 , and 93 patients were included , respectively , in the WA , SET , and SET with feedback groups , and data for 83 , 93 , and 76 , respectively , could be analyzed . The median ( interquartile range ) change in walking distance between 12 months and baseline in meters was 110 ( 0 - 300 ) in the WA group , 310 ( 145 - 995 ) in the SET group , and 360 ( 173 - 697 ) in the SET with feedback group ( P WIQ scores and relevant domains of the SF-36 improved statistically significantly in the SET groups . CONCLUSIONS SET is more effective than WA in improving walking distance , WIQ scores , and quality of life for patients with intermittent claudication . Additional feedback with an accelerometer did not result in further improvement . SET programs should be made available for all patients with intermittent claudication", "Symptoms of intermittent claudication ( IC ) can be relieved by lifestyle modification , medications , and walking exercises . The intensity of the walking exercise is still debatable . The goal of this study was to determine the effects of accommodating pain-free walking exercise therapy program length on pain-free walking . A descriptive , longitudinal study with repeated measures of exercise capacity was conducted . An IC question naire was administered to assess IC signs , symptoms , and lifestyle . Walking was performed on a treadmill for 30 to 50 minutes below the participant 's individualized walking pain threshold . The study included patients diagnosed with IC due to peripheral arterial disease . All participants were r and omly assigned to three groups . Group A ( n = 28 ) participated in the walking program for 2 - 9 weeks , group B ( n = 30 ) for 10 - 14 weeks , and group C ( n = 26 ) for 15 - 94 weeks . The main outcome measure of the study was to determine changes in exercise capacity : walking distance ( miles ) , walking duration ( minutes ) , and walking speed ( mph ) . Group A increased the amount of distance , duration , and speed walked from pretest to posttest by 80 % ( P amount of distance , duration , and speed walked from pretest to posttest by 122 % ( P amount of distance , duration , and speed walked from pretest to posttest by 26 % ( P = .002 ) , 22 % ( P = .002 ) , and 5 % ( P = .541 ) respectively . We reached the conclusion that a walking program of 10 - 14 weeks is optimal for achieving the best improvements in walking distance , duration , and speed", "The purpose of this study was to determine the impact of increased physical activity and cessation of smoking on the natural history of early peripheral arterial disease . We conducted a r and omised controlled trial in Perth , Western Australia , involving 882 men with early peripheral arterial disease identified via population -based screening using the Edinburgh Claudication Question naire and the ankle : brachial index . Members of the control group ( n = 441 ) received \" usual care \" from their general practitioner while members of the intervention group ( n = 441 ) were allocated to a \" stop smoking and keep walking \" regime - a combined community-based intervention of cessation of smoking ( where applicable ) and increased physical activity . Postal follow-up occurred at two and 12 months post-entry into the trial . The main outcome of interest was maximum walking distance . There were no statistically significant differences in the characteristics of the \" intervention \" and \" usual care \" groups at recruitment . Follow-up information at two and 12 months was available for 85 % and 84 % of participants , respectively . At 12 months , more men allocated to the intervention group had improved their maximum walking distance ( 23 % vs 15 % ; chi2 = 9.74 , df = 2 , p = 0.008 ) . In addition , more men in the intervention group reported walking more than three times per week for recreation ( 34 % vs 25 % , p = 0.01 ) . Although not statistically significant , more men in the intervention group who were smokers when enrolled in the trial had stopped smoking ( 12 % vs 8 % , p = 0.43 ) . It is concluded that referral of older patients with intermittent claudication to established physiotherapy programs in the community can increase levels of physical activity and reduce disability related to peripheral arterial disease . A combination of simple and safe interventions that are readily available in the community through physiotherapists and general practitioners has the potential to improve early peripheral arterial disease", "OBJECTIVES To compare percutaneous transluminal angioplasty ( PTA ) against exercise training in the treatment of stable claudication . DESIGN Prospect i ve , r and omised trial . MATERIAL S Fifty-six patients with unilateral , stable , lower limb claudication assessed prior to r and omisation , at 3 monthly intervals for 15 months , and at approximately 6 years follow-up . Thirty-seven patients were available for long term review . OUTCOME MEASURES Ankle/brachial pressure index ( ABPI ) , treadmill claudication and maximum walking distances , percentage fall in ankle systolic pressure after exercise . RESULTS Significant increases were seen in ABPI in the patients treated with PTA at all assessment to 15 months . However in terms of improved walking performance , the most significant changes in claudication and maximum walking distance were seen in the exercise training group . At long term follow-up , there was no significant difference between the groups . Subgroup analysis by angiographic site of disease showed greater functional improvement in those patients with disease confined to the superficial femoral artery treated by exercise training . The overall prognosis for the whole group of patients was benign , with only two ( 4 % ) undergoing amputation . CONCLUSIONS Exercise training confers a greater improvement in claudication and maximum walking distance than PTA , especially in patients with disease confined to the superficial femoral artery", "The purpose of the study was to determine whether patients who participated in an intervention program would improve exercise and foot-care habits , reduce smoking , and would , in turn , have fewer PVD-related illnesses than patients not exposed to the intervention . Eighty-six patients with ankle/ brachial pressure indices of less than 1.0 on one or both legs were r and omly assigned to a study ( N=42 ) or control ( N=44 ) group . All patients were assessed on a variety of health-related and activity behaviors prior to and again 26 weeks after enrollment in the study . Study patients who participated in the intervention worked with professionals on selecting programs design ed to modify and improve their smoking , exercise , and / or foot-care habits . At the end of 26 weeks , chi-square analysis showed no significant differences between study and control groups on change in smoking and foot care , although the results were in the anticipated direction . Study patients who chose to increase their exercise showed greater increase than control patients in frequency ( p = .001 ) , distance ( p = .007 ) , and length ( p = .002 ) of walks . Although behaviors were modified , especially in the area of exercise , it was felt that longer interventions on a larger sample size are needed", "The Claudication : Exercise vs Endoluminal Revascularization ( CLEVER ) Study is a prospect i ve multicenter r and omized clinical trial design ed to compare the relative clinical and cost-effectiveness of invasive revascularization with stents to supervised exercise rehabilitation in a cohort with moderate to severe claudication due to aortoiliac insufficiency . The study is currently enrolling at twenty-eight sites in the US and Canada . Enrollment of 217 participants is planned , with data collected at baseline , six months , and 18 months . The primary study endpoint is maximum walking duration ( MWD ) on a grade d treadmill test ; secondary endpoints include community-based walking , markers of cardiovascular disease risk ( body mass index , waist circumference , blood pressure , lipid profile , glucose tolerance , and plasma fibrinogen ) , health-related quality of life , and cost effectiveness . There are currently sixty r and omized participants ; recruitment is projected to end in July 2010 and final study results reported in June 2012", "BACKGROUND Peripheral arterial occlusive disease ( PAOD ) at II stage results in a moderate to severe impairment in walking ability . Aim of this study , controlled and r and omized , was to evaluate the efficacy of an intensive 4 weeks exercise training in PAOD followed by a six-month period and to analyse the risk factors for atherosclerosis and the site of the lesion for possible predictors of result outcome . METHODS Patients with PAOD were included in the study ( ankle/arm ratio claudication distance ( ICD ) absolute claudication distance ( ACD ) a supervised walking exercise ( mean ICD 121.8 m , ACD 289.7 m ) and 20 to a non exercising control group ( ICD 111.6 m , ACD 230.1 m ) . Both groups were tested at 4 weeks ( T1 ) and 6 months ( T2 ) . Training group was enrolled in a 4-week supervised training program . RESULTS In the training group 10 % of patients became asymptomatic ( > 1000 m ) . At T1 ICD increased 141 % ( p ACD was with low-pain-claudication > 1000 m in 50 % , at T2 ICD was 200 % ( p ICD and ACD . Control group has a no significant increase of ICD and ACD at T1 and T2 . Only arterial hypertension and intermittent claudication severity emerged as negative predictive factors for the results of training . CONCLUSIONS Vascular training produces a significant and lasting improvement in walking distance in PAOD", "The purpose of this study was to examine the effects of a 12month exercise program on lower limb movement variability in patients with peripheral arterial disease ( PAD ) . Participants ( n=21 ) with an appropriate history of PAD and intermittent claudication ( IC ) volunteered for this study and were r and omly allocated to either a control group ( CPAD-IC ) ( n=11 ) , which received normal medical therapy and a treatment group ( TPAD-IC ) ( n=10 ) , which received normal medical therapy treatment and a 12month supervised exercise program . All participants underwent 2D joint angular kinematic analysis during normal walking to assess lower limb movement variability and walking speed . Between-group differences were analyzed via mixed measures ANOVA . The 12month supervised exercise program made no significant impact on the lower limb movement variability or walking speed of the TPAD-IC group as determined by either intralimb joint coordination or single joint analysis techniques . Long term supervised exercise programs do not appear to influence the lower limb movement variability of PAD-IC patients ", "INTRODUCTION Though being physically active has associated with a healthier ankle-brachial index ( ABI ) in observational studies , ABI usually does not change with exercise training in patients with peripheral artery disease ( PAD ) . Less is known about the effect of exercise training on ABI in patients without PAD but at high risk due to the presence of type 2 diabetes ( T2DM ) . METHODS Participants ( n = 140 ) with uncomplicated T2DM , and without known cardiovascular disease or PAD , aged 40 - 65 years , were r and omized to supervised aerobic and resistance training 3 times per week for 6 months or to a usual care control group . ABI was measured before and after the intervention . RESULTS Baseline ABI was 1.02 ± 0.02 in exercisers and 1.03 ± 0.01 in controls ( p = 0.57 ) . At 6 months , exercisers vs. controls improved ABI by 0.04 ± 0.02 vs. -0.03 ± 0.02 ( p = 0.001 ) . This change was driven by an increase in ankle pressures ( p no change in brachial pressures ( p = 0.747 ) . In subgroup analysis , ABI increased in exercisers vs. controls among those with baseline ABI baseline ABI ≥1.0 ( p = 0.085 ) . The prevalence of ABI between 1.0 and 1.3 increased from 63 % to 78 % in exercisers and decreased from 62 % to 53 % in controls . Increased ABI correlated with decreased HbA1c , systolic and diastolic blood pressure , but the effect of exercise on ABI change remained significant after adjustment for these changes ( β = 0.061 , p = 0.004 ) . CONCLUSION These data suggest a possible role for exercise training in the prevention or delay of PAD in T2DM , particularly among those starting with an ABI < 1.0 . Clinical trials.gov Registry Number : NCT00212303", "Objective To analyze the posteffects of a single bout of resistance exercise on cardiovascular parameters in patients with peripheral artery disease ( PAD ) . Design R and omized cross-over . Material s and methods Seventeen PAD patients performed two experimental sessions : control ( C ) and resistance exercise ( R ) . Both sessions were identical ( eight exercises , 3 × 10 repetitions ) , except that the R session was performed with an intensity between 5 and 7 in the OMNI-RES scale and the C session was performed without any load . Systolic blood pressure ( BP ) , diastolic BP , heart rate , and rate – pressure product ( RPP ) were measured for 1 h after the interventions in the laboratory and during 24-h using ambulatory BP monitoring . Results After the R session , systolic BP ( greatest reduction : −6±2 mmHg , P ) and RPP ( greatest reduction : −888±286 mmHg × bpm ; P exercise , BP , heart rate , and RPP product were similar ( P>0.05 ) between R and C sessions . BP load , nocturnal BP fall , and morning surge were also similar between R and C sessions ( P>0.05 ) . Conclusion A single bout of resistance exercise decreased BP and cardiac work for 1 h after exercise under clinical conditions , and did not modify ambulatory cardiovascular variables during 24 h in patients with PAD", "Previous studies have demonstrated that supervised strength training ( ST ) or walking training ( WT ) improve walking capacity in patients with claudication . However , it remains unknown whether these improvements would be sustained over a subsequent unsupervised period . This article reports the findings of a study to analyze whether the improvements in walking capacity , achieved with a supervised ST or WT , would be sustained over a subsequent unsupervised therapy period in patients with claudication . Patients were initially r and omized to supervised exercise consisting of ST ( n = 15 ) or WT ( n = 15 ) for 12 weeks . After this period , 12 patients in each group consented to be followed for an additional 12 weeks of unsupervised therapy . Initial claudication distance ( ICD ) and total walking distance ( TWD ) were measured at baseline , after the supervised period ( Week 12 ) and after the unsupervised period ( Week 24 ) . In comparison with baseline values , both groups similarly increased ICD and TWD at Week 12 . From Week 12 to Week 24 , both groups similarly decreased ICD ( ST : -55 ± 110 m and WT : -82 ± 142 m , P = .04 ) and TWD ( ST : -68 ± 186 m and WT : -128 ± 112 m , P groups , ICD ( ST : + 126 ± 149 m and WT : + 50 ± 167 m , P = .01 ) and TWD ( ST : + 104 ± 162 m and WT : + 45 ± 139 m , P = .01 ) at Week 24 remained greater than baseline values . The conclusion is that supervised ST or WT followed by an unsupervised therapy period similarly decreased walking capacity in patients with claudication . However , after the unsupervised period , walking capacity remained at a higher level than before the onset of the supervised exercise-training period", "BACKGROUND It is not clear whether subgroups of patients with peripheral artery disease ( PAD ) and claudication respond more favorably to exercise rehabilitation than others . We determined whether sex and diabetes were factors associated with the response to exercise rehabilitation in patients with claudication . METHODS Eighty patients were r and omized to home-based and supervised exercise programs , and 60 finished with complete exercise intervention data . Exercise consisted of intermittent walking to near maximal claudication pain for 3 months . Primary outcome measures included claudication onset time ( COT ) and peak walking time . Patients were partitioned into diabetic and nondiabetic groups and then further partitioned by sex to form four groups . RESULTS Overall , exercise adherence was high ( 84 % ) , and there was no significant difference ( P > .05 ) in the amount of exercise completed among the four groups . All groups had significant improvements ( P COT and peak walking time after exercise rehabilitation , except for diabetic women ( P > .05 ) . Only 37 % of women with diabetes had an increase in COT compared with 100 % of men with diabetes ( P Women with PAD and claudication , particularly those with diabetes , represent a vulnerable subgroup of patients who respond poorly to a program of exercise rehabilitation . Diabetic women with PAD and claudication may need a greater dose of exercise or another intervention separate from or in combination with exercise to elicit improvements in claudication measures that are similar to nondiabetic women and to diabetic and nondiabetic men", "Abstract The CLaudication : Exercise Vs Endoluminal Revascularization ( CLEVER ) study is the first r and omized , controlled , clinical , multicenter trial that is evaluating a supervised exercise program compared with revascularization procedures to treat claudication . In this report , the methods and dissemination techniques of the supervised exercise training intervention are described . A total of 217 participants are being recruited and r and omized to one of three arms : ( 1 ) optimal medical care ; ( 2 ) aortoiliac revascularization with stent ; or ( 3 ) supervised exercise training . Of the enrolled patients , 84 will receive supervised exercise therapy . Supervised exercise will be administered according to a protocol design ed by a central CLEVER exercise training committee based on vali date d methods previously used in single center r and omized control trials . The protocol will be implemented at each site by an exercise committee member using training methods developed and st and ardized by the exercise training committee . The exercise training committee review s progress and compliance with the protocol of each participant weekly . In conclusion , a multicenter approach to disseminate the supervised exercise training technique and to evaluate its efficacy , safety and cost-effectiveness for patients with claudication due to peripheral arterial disease ( PAD ) is being evaluated for the first time in CLEVER . The CLEVER study will further establish the role of supervised exercise training in the treatment of claudication result ing from PAD and provide st and ardized methods for use of supervised exercise training in future PAD clinical trials as well as in clinical practice", "Objective : To compare the outcomes of home-based ( using the Heart Manual ) and centre-based cardiac rehabilitation programmes . Design : R and omised controlled trial and parallel economic evaluation . Setting : Predominantly inner-city , multi-ethnic population in the West Midl and s , Engl and . Patients : 525 patients referred to four hospitals for cardiac rehabilitation following myocardial infa rct ion or coronary revascularisation . Interventions : A home-based cardiac rehabilitation programme compared with centre-based programmes . Main outcome measures : Smoking cessation , blood pressure ( systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) ) , total cholesterol ( TC ) and high-density lipoprotein (HDL)-cholesterol , psychological status ( HADS anxiety and depression ) and exercise capacity ( incremental shuttle walking test , ISWT ) measured at 12 months . Health service re source use , quality of life utility and costs were quantified . Results : There were no significant differences in the main outcomes when the home-based was compared with the centre-based programme at 12 months . Adjusted mean difference ( 95 % CI ) for SBP was 1.94 mm Hg ( −1.1 to 5.0 ) ; DBP 0.42 mm Hg ( −1.25 to 2.1 ) ; TC 0.1 mmol/l ( −0.05 to 0.24 ) ; HADS anxiety −0.02 ( −0.69 to 0.65 ) ; HADS depression −0.35 ( −0.95 to 0.25 ) ; distance on ISWT −21.5 m ( −48.3 to 5.2 ) . The relative risk of being a smoker in the home arm was 0.90 . The cost per patient to the NHS was significantly higher in the home arm at £ 198 , ( 95 % CI 189 to 208 ) compared to £ 157 ( 95 % CI 139 to 175 ) in the centre-based arm . However when the patients ’ cost of travel was included , these differences were no longer significant . Conclusions A home-based cardiac rehabilitation programme does not produce inferior outcomes when compared to traditional centre-based programmes as provided in the United Kingdom", "OBJECTIVES The Exercise Therapy in Peripheral Arterial Disease ( EXITPAD ) study has shown supervised exercise therapy ( SET ) to be more effective regarding walking distance and quality of life than a ' go home and walk ' advice ( WA ) for patients with intermittent claudication . The present study aims to assess the cost-effectiveness of SET versus WA . PATIENTS AND METHODS Data from the EXITPAD study , a 12-month r and omised controlled trial in 304 patients with claudication , was used to study the proportion of costs to walking distance and quality of life . Two different incremental cost-effectiveness ratios ( ICERs ) were calculated for SET versus WA : costs per extra metre on the treadmill test , and costs per quality -adjusted life year ( QALY ) . QALYs were based on utilities derived from the EuroQoL-5 dimensions ( EQ-5D ) . RESULTS Mean total costs were higher for SET than for WA ( 3407 versus 2304 Euros ) , mainly caused by the costs of exercise therapy . The median walking distance was 620 m for SET and 400 m for WA . QALYs were 0.71 for SET and 0.67 for WA . All differences were statistically significant . The ICER for cost per extra metre on the 12-month treadmill test was € 4.08 . For cost per QALY , the ICER was € 28,693 . CONCLUSION At a willingness-to-pay threshold of € 40,000 per QALY , SET likely is a cost-effective therapeutic option for patients with claudication" ]	411889de-06ff-11f0-808a-c43d1ab1c353
PURPOSE To up date American Society of Hematology/American Society of Clinical Oncology recommendations for use of erythropoiesis-stimulating agents ( ESAs ) in patients with cancer . METHODS An Up date Committee review ed data published between January 2007 and January 2010 . MEDLINE and the Cochrane Library were search ed . RESULTS The literature search yielded one new individual patient data analysis and four literature -based meta-analyses , two systematic review s , and 13 publications reporting new results from r and omized controlled trials not included in prior or new review s. RECOMMENDATIONS For patients undergoing myelosuppressive chemotherapy who have a hemoglobin ( Hb ) level less than 10 g/dL , the Up date Committee recommends that clinicians discuss potential harms ( eg , thromboembolism , shorter survival ) and benefits ( eg , decreased transfusions ) of ESAs and compare these with potential harms ( eg , serious infections , immune-mediated adverse reactions ) and benefits ( eg , rapid Hb improvement ) of RBC transfusions . Individual preferences for assumed risk should contribute to shared decisions on managing chemotherapy-induced anemia . The Committee caution s against ESA use under other circumstances . If used , ESAs should be administered at the lowest dose possible and should increase Hb to the lowest concentration possible to avoid transfusions . Available evidence does not identify Hb levels ≥ 10 g/dL either as thresholds for initiating treatment or as targets for ESA therapy . Starting doses and dose modifications after response or nonresponse should follow US Food and Drug Administration-approved labeling . ESAs should be discontinued after 6 to 8 weeks in nonresponders . ESAs should be avoided in patients with cancer not receiving concurrent chemotherapy , except for those with lower risk myelodysplastic syndromes . Caution should be exercised when using ESAs with chemotherapeutic agents in diseases associated with increased risk of thromboembolic complications . Table 1 lists detailed recommendations	[ "Chronic anemia of cancer can be corrected in approximately 50 % of the cases by treatment with recombinant human erythropoietin ( rHuEPO ) . Early prediction of responsiveness would avoid the emotional and financial burden of ineffective medical intervention . Eighty patients with chronic anemia of cancer undergoing treatment with rHuEPO ( 150 U/kg , 3 times per week by subcutaneous injection ; after 6 weeks without response , 300 U/kg ) participated in this study . Response was defined as a gain of at least 2 g/dL hemoglobin ( Hb ) within 12 weeks . Multivariate discriminant analysis and logistic regression analysis of response were performed on routine blood tests ; serum levels of EPO , iron , ferritin , transferrin , and its receptor ; World Health Organization ( WHO ) performance status ; various cytokines ; neopterin ; stem cell factor ; C-reactive protein ; and alpha 1-antitrypsin . At baseline , none of these factors showed sufficient prognostic power . The following predictive algorithm was developed : ( 1 ) If after 2 weeks of therapy both the serum EPO level is > or = 100 mU/mL and Hb concentration has not increased by at least 0.5 g/dL , unresponsiveness of the patient is very likely ( predictive power , 93 % ) ; otherwise , response may be predicted with an accuracy of 80 % . ( 2 ) If both the serum level of EPO is less than 100 mU/mL and Hb concentration has increased by > or = 0.5 g/dL , response is highly probable ( predictive power , 95 % ) . ( 3 ) Alternatively , a serum ferritin level of > or = 400 ng/mL after 2 weeks of rHuEPO therapy strongly indicates unresponsiveness ( predictive power , 88 % ) , whereas a level less than 400 ng/mL suggests response in 3 of 4 patients", "Inflammatory cytokines are important predictors of cardiovascular mortality especially in patients with chronic kidney disease . Here we explored the relationship of anemia and epoetin treatment to inflammatory cytokine levels in patients with chronic kidney disease . One hundred non-dialysis patients with chronic kidney disease over 18 years of age were evenly split into anemic and non-anemic cohorts . Of the 50 anemic patients , 23 were receiving erythropoiesis stimulating agents treatments . Levels of tumor necrosis factor (TNF)-alpha were found to be significantly higher and serum albumin was significantly lower with trends towards higher interleukin (IL)-6 and IL-8 in anemic compared to non-anemic patients . Further analysis by multiple logistic regression found that anemic patients treated with erythropoiesis stimulating agents had significantly higher odds for the upper two quartiles for IL-6 , IL-8 and TNF-alpha compared to non-anemic patients . Our study found that the anemia of chronic kidney disease was associated with up regulation of TNF-alpha , and possibly IL-6 and IL-8 along with increased levels of these proinflammatory cytokines in patients treated with epoetin", "Previous phase I-II clinical trials have shown that recombinant human erythropoietin ( rHuEpo ) can ameliorate anemia in a portion of patients with multiple myeloma ( MM ) and non-Hodgkin 's lymphoma ( NHL ) . Therefore , we performed a r and omized controlled multicenter study to define the optimal initial dosage and to identify predictors of response to rHuEpo . A total of 146 patients who had hemoglobin ( Hb ) levels entered this trial . Patients were r and omized to receive 1,000 U ( n = 31 ) , 2,000 U ( n = 29 ) , 5,000 U ( n = 31 ) , or 10,000 U ( n = 26 ) of rHuEpo daily subcutaneously for 8 weeks or to receive no therapy ( n = 29 ) . Of the patients , 84 suffered from MM and 62 from low- to intermediate- grade NHL , including chronic lymphocytic leukemia ; 116 of 146 ( 79 % ) received chemotherapy during the study . The mean baseline Hb level was 9.4 + /- 1.0 g/dL. The median serum Epo level was 32 mU/mL , and endogenous Epo production was found to be defective in 77 % of the patients , as judged by a value for the ratio of observed-to-predicted serum Epo levels ( O/P ratio ) of efficacy . The median average increase in Hb levels per week was 0.04 g/dL in the control group and -0.04 ( P = .57 ) , 0.22 ( P = .05 ) , 0.43 ( P = .01 ) , and 0.58 ( P = .0001 ) g/dL in the 1,000 U , 2,000 U , 5,000 U , and 10,000 U groups , respectively ( P values versus control ) . The probability of response ( delta Hb > or = 2 g/dL ) increased steadily and , after 8 weeks , reached 31 % ( 2,000 U ) , 61 % ( 5,000 U ) , and 62 % ( 10,000 U ) , respectively . Regression analysis using Cox 's proportional hazard model and classification and regression tree analysis showed that serum Epo levels and the O/P ratio were the most important factors predicting response in patients receiving 5,000 or 10,000 U. Approximately three quarters of patients presenting with Epo levels inappropriately low for the degree of anemia responded to rHuEpo , whereas only one quarter of those with adequate Epo levels did so . Classification and regression tree analysis also showed that doses of 2,000 U daily were effective in patients with an average platelet count greater than 150 x 10(9)/L. About 50 % of these patients are expected to respond to rHuEpo . Thus , rHuEpo was safe and effective in ameliorating the anemia of MM and NHL patients who showed defective endogenous Epo production . From a practical point of view , we conclude that the decision to use rHuEpo in an individual anemic patient with MM or NHL should be based on serum Epo levels , whereas the choice of the initial dosage should be based on residual marrow function", "This phase 3 prospect i ve r and omized trial evaluated the efficacy and long-term safety of erythropoietin ( EPO ) with or without granulocyte colony-stimulating factor plus supportive care ( SC ; n = 53 ) versus SC alone ( n = 57 ) for the treatment of anemic patients with lower-risk myelodysplastic syndromes . The response rates in the EPO versus SC alone arms were 36 % versus 9.6 % , respectively , at the initial treatment step , 47 % in the EPO arm , including subsequent steps . Responding patients had significantly lower serum EPO levels ( 45 % vs 5 % responses for levels or = 200 mU/mL ) and improvement in multiple quality -of-life domains . With prolonged follow-up ( median , 5.8 years ) , no differences were found in overall survival of patients in the EPO versus SC arms ( median , 3.1 vs 2.6 years ) or in the incidence of transformation to acute myeloid leukemia ( 7.5 % and 10.5 % patients , respectively ) . Increased survival was demonstrated for erythroid responders versus nonresponders ( median , 5.5 vs 2.3 years ) . Flow cytometric analysis showed that the percentage of P-glycoprotein(+ ) CD34(+ ) marrow blasts was positively correlated with longer overall survival . In comparison with SC alone , patients receiving EPO with or without granulocyte colony-stimulating factor plus SC had improved erythroid responses , similar survival , and incidence of acute myeloid leukemia transformation", "Health-related quality of life ( HrQOL ) assessment s are gaining importance as outcome measures in cancer clinical trials . A recently published clinical trial reported statistically significant ( P HrQOL scores following the administration of recombinant human erythropoietin ( r-HuEPO , epoetin alfa ) versus placebo to anaemic cancer patients who received non-platinum chemotherapy . This study employed five cancer-specific HrQOL instruments . Hb and HrQOL data from this trial were analysed to estimate the minimally important difference ( MID ) in HrQOL measures that could be interpreted as clinical ly meaningful , with Hb level selected as the best external st and ard . Patients were assigned to two groups : improved ( Hb increases of > /=1 g/dL ) or stable ( change in Hb of-1 g/dL to HrQOL in the improved group versus the stable group . By this analysis , the differences in HrQOL scores between the epoetin alfa group and the placebo group were clinical ly important for all Hb-sensitive , cancer-specific HrQOL evaluations . Linear regression analyses performed to provide estimates of the MID for specific values of Hb change confirmed that the differences in HrQOL scores between patient groups were clinical ly significant . These analyses were repeated using a data set from a separate clinical trial , which further supported the conclusion that observed HrQOL changes demonstrated in the multicentre , double-blind study were clinical ly important . These methods provide one means for interpreting the clinical relevance of changes in HrQOL evaluated in clinical trials", "PURPOSE To exp and on our experience with the combination of paclitaxel , fluorouracil , hydroxyurea , and twice daily irradiation ( T-FHX ) and to assess the impact of weekly administration of erythropoietin ( r-HuEpo ) on transfusion requirements , we conducted a Phase II multi-institutional trial with a simplified 1-h paclitaxel infusion schedule and r and omized patients to receive weekly doses of r-HuEpo . PATIENTS AND METHODS A total of 90 patients with locally advanced head and neck cancers ( stage IV , 96 % ; N(2)/N(3 ) , 66 % ) were treated on a regimen of 1-h infusion of paclitaxel ( 100 mg/m(2)/day , day 1 ) , 120-h infusion of 5-fluorouracil ( 600 mg/m(2)/day , days 0 - 5 ) ; hydroxyurea 500 mg p.o . every 12 h for 11 doses ; and radiation 150cGy bid , days 1 - 5 of each 14-day cycle repeated for five cycles over 10 weeks ( 7200 - 7500 cGy ) . Before initiating therapy , patients were r and omized to receive r-HuEpo 40,000 IU s.c . once weekly . RESULTS At median follow-up of 40 months , 3-year progression-free survival is 62 % , locoregional control is 84 % , and systemic control is 79 % . Overall survival is 59 % . Anemia , leucopenia , dermatitis , and mucositis were the most frequent grade 3 or 4 toxicities . Patients r and omized to erythropoietin experienced less grade 2/3 anemia ( 52 versus 77 % ; P = 0.02 ) , but transfusion requirements were not significantly different . CONCLUSIONS T-FHX is an active and tolerable regimen inducing local tumor control and promising survival with organ preservation in high-risk patients . One h infusion of paclitaxel simplified the regimen without compromising efficacy . Addition of erythropoietin does not reduce the need for transfusion with this nonplatinum-containing regimen . T-FHX should be advanced to a r and omized trial and compared with a cisplatin-based concomitant regimen", "Despite the prevalence of anemia in cancer , recombinant erythropoietin ( Epo ) has declined in use because of recent Phase III trials showing more rapid cancer progression and reduced survival in subjects r and omized to Epo . Since Epo receptor ( EpoR ) , Jak2 , and Hsp70 are well-characterized mediators of Epo signaling in erythroid cells , we hypothesized that Epo might be especially harmful in patients whose tumors express high levels of these effectors . Because of the insensitivity of immunohistochemistry for detecting low level EpoR protein , we developed assays to measure levels of EpoR , Jak2 and Hsp70 mRNA in formalin-fixed paraffin-embedded ( FFPE ) tumors . We tested 23 archival breast tumors as well as 136 archival head and neck cancers from ENHANCE , a Phase III trial of 351 patients r and omized to Epo versus placebo concomitant with radiotherapy following complete resection , partial resection , or no resection of tumor . EpoR , Jak2 , and Hsp70 mRNA levels varied > 30-fold , > 12-fold , and > 13-fold across the breast cancers , and > 30-fold , > 40-fold , and > 30-fold across the head and neck cancers , respectively . Locoregional progression-free survival ( LPFS ) did not differ among patients whose head and neck cancers expressed above- versus below-median levels of EpoR , Jak2 or Hsp70 , except in the subgroup of patients with unresected tumors ( n = 28 ) , where above-median EpoR , above-median Jak2 , and below-median Hsp70 mRNA levels were all associated with significantly poorer LPFS . Our results provide a framework for exploring the relationship between Epo , cancer progression , and survival using archival tumors from other Phase III clinical trials", "Background Several studies have shown that darbepoetin alfa , an erythropoiesis-stimulating agent ( ESA ) , can reduce transfusions and increase hemoglobin ( Hb ) levels in patients with chemotherapy-induced anemia ( CIA ) . Recent safety concerns , however , have prompted changes to ESA product information . In the European Union and United States , ESA therapy initiation for CIA is now recommended at a Hb level ≤10 g/dL. The present exploratory analysis examined how ESA initiation at this Hb level may impact patient care . Methods Data from a phase 3 r and omized trial were retrospectively reanalyzed . CIA patients with nonmyeloid malignancies were r and omized 1:1 to 500 mcg darbepoetin alfa every three weeks ( Q3W ) or 2.25 mcg/kg darbepoetin alfa weekly ( QW ) for 15 weeks . A previously published report from this trial showed Q3W dosing was non-inferior to QW dosing for reducing transfusions from week 5 to end-of-the-treatment period ( EOTP ) . In the present analysis , outcomes were reanalyzed by baseline Hb included transfusion rates , Hb outcomes , and safety profiles . Results This study reanalyzed 351 and 354 patients who initiated ESA therapy at a baseline Hb of 10 g/dL or ≥10 g/dL , respectively . From week 5 to EOTP , the estimated Kaplan-Meier transfusion incidence ( Q3W vs QW ) was lower in the ≥10 g/dL baseline-Hb group ( 14 % vs 21 % ) compared with the a mean Hb ≥11 g/dL. The Kaplan-Meier estimate of percentage of patients ( Q3W vs QW ) who achieved Hb ≥11 g/dL from week 1 to EOTP was 90 % vs 85 % in the ≥10 g/dL baseline-Hb group and 54 % vs 57 % in the maintained mean Hb levels and had similar safety profiles , though more patients in the ≥10 g/dL baseline-Hb group reached the threshold Hb of ≥13 g/dL. Conclusion In this exploratory analysis , darbepoetin alfa Q3W and QW raised Hb levels and maintained mean Hb at transfusions and faster anemia correction . Additional studies should prospect ively evaluate the relationship between Hb levels at ESA initiation and outcomes .Trial Registration Clinical Trials.gov Identifier NCT00118638", "Anemia result ing from cancer or its treatment is an important clinical problem increasingly treated with the recombinant hematopoietic growth factor erythropoietin . To address uncertainties regarding indications and efficacy , the American Society of Clinical Oncology and the American Society of Hematology developed an evidence -based clinical practice guideline for the use of epoetin in patients with cancer . The guideline panel found good evidence to recommend use of epoetin as a treatment option for patients with chemotherapy-associated anemia with a hemoglobin ( Hgb ) concentration below 10 g/dL. Use of epoetin for patients with less severe anemia ( Hgb level below 12 g/dL but never below 10 g/dL ) should be determined by clinical circumstances . Good evidence from clinical trials supports the use of subcutaneous epoetin thrice weekly ( 150 U/kg ) for a minimum of 4 weeks . Less strong evidence supports an alternative weekly ( 40 000 U/wk ) dosing regimen , based on common clinical practice . With either administration schedule , dose escalation should be considered for those not responding to the initial dose . In the absence of response , continuing epoetin beyond 6 - 8 weeks does not appear to be beneficial . Epoetin should be titrated once the hemoglobin concentration reaches 12 g/dL. Evidence from one r and omized controlled trial supports use of epoetin for patients with anemia associated with low-risk myelodysplasia not receiving chemotherapy ; however , there are no published high- quality studies to support its use for anemia in other hematologic malignancies in the absence of chemotherapy . Therefore , for anemic patients with hematologic malignancies it is recommended that physicians initiate conventional therapy and observe hematologic response before considering use of epoetin", "PURPOSE To investigate the effect of recombinant human erythropoietin ( epoetin beta ) on anemia , transfusion need , and quality of life ( QOL ) in severely anemic patients with low- grade non-Hodgkin 's lymphoma ( NHL ) , chronic lymphocytic leukemia ( CLL ) , or multiple myeloma ( MM ) . PATIENTS AND METHODS Transfusion-dependent patients with NHL ( n = 106 ) , CLL ( n = 126 ) , or MM ( n = 117 ) and a low serum erythropoietin concentration were r and omized to receive epoetin beta 150 IU/kg or placebo subcutaneously three times a week for 16 weeks . Primary efficacy criteria were transfusion-free and transfusion- and severe anemia-free survival ( hemoglobin [ Hb ] > 8.5 g/dL ) between weeks 5 to 16 . Response was defined as an increase in Hb > or = 2 g/dL with elimination of transfusion need . QOL was assessed by the Functional Assessment of Cancer Therapy scale . RESULTS Transfusion-free ( P = .0012 ) survival and transfusion- and severe anemia-free survival ( P = .0001 ) were significantly greater in the epoetin beta group versus placebo ( Wald chi(2 ) test ) , giving a relative risk reduction of 43 % and 51 % , respectively . The response rate was 67 % and 27 % in the epoetin beta versus the placebo group , respectively ( P QOL significantly improved in the epoetin beta group compared with placebo ( P Hb concentration ( > or = 2 g/dL ) . A target Hb that could be generally recommended could not be identified . CONCLUSION Many severely anemic and transfusion-dependent patients with advanced MM , NHL , and CLL and a low performance status benefited from epoetin therapy , with elimination of severe anemia and transfusion need , and improvement in QOL", "BACKGROUND In the United States , darbepoetin alfa ( Aranesp ) is often used to treat patients with chemotherapy-induced anemia using weekly or every-2-week administration schedules . In Europe , darbepoetin alfa is used either weekly or in every-3-week dosing . The every-3-week schedule can be synchronized with many chemotherapy regimens , result ing in fewer visits and reducing burden to patients , but the safety and efficacy of this regimen have not been clear . METHODS A r and omized , double-blind , double-dummy , active-controlled phase 3 trial was performed in 110 European centers . Eligible patients ( age > or = 18 years ) were anemic ( hemoglobin level Patients were r and omly assigned 1:1 to darbepoetin alfa treatment every 3 weeks ( 500-microg dose ) or weekly ( 2.25-microg/kg ) for 15 weeks . We compared red blood cell transfusion incidence among the two arms from week 5 to the end of the treatment phase using a noninferiority study design . Noninferiority was determined if the upper limit of the 95 % confidence interval ( CI ) for the difference in blood transfusions between groups , calculated using Kaplan-Meier methods , did not exceed 12.5 % , a margin based on previous placebo-controlled studies . RESULTS A total of 705 patients were r and omly assigned , and 672 remained in the study at week 5 . Fewer patients in the every-3-week arm than in the weekly arm received blood transfusions from week 5 to the end of the treatment phase ( unadjusted Kaplan-Meier estimates = 23 % versus 30 % , difference = -6.8 % ; 95 % CI = -13.6 to 0.1 ) . Percentages of patients achieving the target hemoglobin level ( > or = 11 g/dL , consistent with evidence -based practice guidelines ) were 84 % ( every 3 weeks ) and 77 % ( weekly ) . The frequency of cardiovascular/thromboembolic adverse events was 8 % in both groups , and safety was comparable . CONCLUSIONS Patients with chemotherapy-induced anemia can safely and effectively be treated with 500 microg of darbepoetin alfa every 3 weeks", "PURPOSE To determine whether weekly epoetin alfa could improve hemoglobin ( HgB ) levels , reduce RBC transfusions , and improve quality of life ( QOL ) in patients with advanced cancer and with anemia after receiving myelosuppressive chemotherapy . PATIENTS AND METHODS This double-blind , placebo-controlled study r and omly assigned patients to placebo or epoetin alfa ( Ortho Biotech , Bridgewater , NJ ) 40,000 U subcutaneous weekly for 16 weeks . QOL , HgB , and RBC transfusions were measured pretreatment and monthly . RESULTS The study accrued 344 patients ; 330 were assessable for efficacy and 305 were assessable for QOL . Placebo-treated patients had a mean increase in HgB of 0.9 g/dL ( range , -3.8 to + 5.3 ) compared with 2.8 g/dL ( range , -2.2 to + 7.5 ) for epoetin-treated patients ( P placebo-treated patients achieved a > or = 2 g/dL HgB increase compared with 72.7 % of epoetin-treated patients ( P incidence of RBC transfusion for placebo and epoetin treatment arms was 39.6 % and 25.3 % ( P = .005 ) , respectively . The placebo group received 256 units of RBCs compared with 127 units in the epoetin group ( P incidence of toxicity in the groups was similar . Changes in the average QOL scores from baseline to the end of the study were similar in the two groups ( P = not significant ) . The HgB responders ( irrespective of treatment arm ) had a mean change in Functional Assessment of Cancer Therapy ( FACT ) fatigue score from a baseline of + 5.1 compared with -2.1 for the nonresponders ( P = .006 ) . CONCLUSION Epoetin alfa significantly improved HgB and reduced transfusions in this patient population . These results support the use of weekly epoetin alfa as an ameliorative agent for cancer-related anemia", "PURPOSE The efficacy and safety of darbepoetin alpha ( DA ) for treating patients with active cancer and anemia not receiving or planning to receive cytotoxic chemotherapy or myelosuppressive radiotherapy was evaluated . PATIENTS AND METHODS Patients with active cancer and anemia not receiving or planning to receive chemotherapy or radiotherapy were enrolled onto a phase III , multicenter , r and omized , placebo-controlled study and administered placebo or DA 6.75 microg/kg every 4 weeks ( Q4W ) for up to 16 weeks with a 2-year follow-up for survival . Patients who completed 16 weeks of treatment could receive the same treatment as r and omized Q4W for an additional 16 weeks . The primary end point was all occurrences of transfusions from weeks 5 through 17 ; safety end points included incidence of adverse events and survival . RESULTS The incidence of transfusions between weeks 5 and 17 was lower in the DA group but was not statistically significantly different from that of placebo . DA was associated with an increased incidence of cardiovascular and thromboembolic events and more deaths during the initial 16-week treatment period . Long-term survival data demonstrated statistically significantly poorer survival in patients treated with DA versus placebo ( P = .022 ) . This effect varied by baseline covariates including , sex , tumor type , and geographic region ; statistical significance diminished ( P = .12 ) when the analysis was adjusted for baseline imbalances or known prognostic factors . CONCLUSION DA was not associated with a statistically significant reduction in transfusions . Shorter survival was observed in the DA arm ; thus , this study does not support the use of erythropoiesis-stimulating agents in this subset of patients with anemia of cancer", "The myelodysplastic syndromes ( MDSs ) are heterogeneous with respect to clinical characteristics , pathologic features , and cytogenetic abnormalities . This heterogeneity is a challenge for evaluating response to treatment . Therapeutic trials in MDS have used various criteria to assess results , making cross- study comparisons problematic . In 2000 , an International Working Group ( IWG ) proposed st and ardized response criteria for evaluating clinical ly significant responses in MDS . These criteria included measures of alteration in the natural history of disease , hematologic improvement , cytogenetic response , and improvement in health-related quality of life . The relevance of the response criteria has now been vali date d prospect ively in MDS clinical trials , and they have gained acceptance in research studies and in clinical practice . Because limitations of the IWG criteria have surfaced , based on practical and reported experience , some modifications were warranted . In this report , we present recommendations for revisions of some of the initial criteria", "PURPOSE To determine whether maintaining HGB levels > or = 12.0 g/dL with recombinant human erythropoietin ( R-HUEPO ) compared to \" st and ard \" treatment ( transfusion for HGB progression-free survival ( PFS ) , overall survival ( OS ) and local control ( LC ) in women receiving concurrent weekly cisplatin and radiation ( CT/RT ) for carcinoma of the cervix . In addition , to determine whether platinum-DNA adducts were associated with clinical characteristics or outcome . METHODS Patients with stage IIB-IVA cervical cancer and HGB were r and omly assigned to CT/RT+/-R-HUEPO ( 40,000 units s.c . weekly ) . R-HUEPO was stopped if HGB > 14.0 g/dL. Endpoints were PFS , OS and LC . Platinum-DNA adducts were quantified using immunocytochemistry assay in buccal cells . RESULTS Between 08/01 and 09/03 , 109 of 114 patients accrued were eligible . Fifty-two received CT/RT and 57 CT/RT+R-HUEPO . The study closed prematurely , with less than 25 % of the planned accrual , due to potential concerns for thromboembolic event ( TE ) with R-HUEPO . Median follow-up was 37 months ( range 9.8 - 50.4 months ) . PFS and OS at 3 years should be 65 % and 75 % for CT/RT and 58 % and 61 % for CT/RT+R-HUEPO , respectively . TE occurred in 4/52 receiving CT/RT and 11/57 with CT/RT+R-HUEPO , not all considered treatment related . No deaths occurred from TE . High-platinum adducts were associated with inferior PFS and LC . CONCLUSION TE is common in cervical cancer patients receiving CT/RT . Difference in TE rate between the two treatments was not statistically significant . The impact of maintaining HGB level > 12.0 g/dL on PFS , OS and LC remains undetermined", "OBJECTIVE The efficacy and safety of weekly administration of epoetin beta ( EPO ) for chemotherapy-induced anemia ( CIA ) patients was evaluated . METHODS One hundred and twenty-two patients with lung cancer or malignant lymphoma undergoing chemotherapy were r and omized to the EPO 36 000 IU group or the placebo group . Hematological response and red blood cell ( RBC ) transfusion requirement were assessed . Quality of life ( QOL ) was assessed using the Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) question naire . RESULTS Mean change in hemoglobin level with EPO increased significantly over placebo ( 1.4 + /- 1.9 g/dl versus -0.8 + /- 1.5 g/dl ; P change in hemoglobin level > or = 2.0 g/dl was higher for EPO than those for placebo ( P proportion of RBC transfusion or hemoglobin level EPO than those for placebo ( P = 0.046 ) . The changes in the FACT-An total Fatigue Subscale Score ( FSS ) were less deteriorated with EPO than those with placebo . Progressive disease ( PD ) did not influence the change in hemoglobin level but there was less decrease in FSS in non-PD patients . No significant differences in adverse events were observed . Thrombovascular events and pure red cell aplasia related to EPO were not observed . Retrospective analysis of survival showing the hazard ratio of EPO to placebo was 0.94 . CONCLUSION Weekly administration of EPO 36 000 IU significantly increased hemoglobin level and ameliorated the decline of QOL in CIA patients over the 8-week administration period", "In myelodysplastic syndromes ( MDS ) , anemia responds to recombinant human erythropoietin ( rHuEPO ) alone and in combination with recombinant human granulocyte-colony-stimulating factor ( rHuGCSF ) in 10 % to 20 % and in 35 % to 40 % of patients , respectively . We r and omly divided 60 patients with low- grade anemic MDS and serum EPO levels lower than 500 IU/L ( 500 mU/mL ) into 2 groups : rHuEPO + rHuG-CSF ( arm A ) and supportive care ( arm B ) . After 12 weeks , those who had erythroid responses were given rHuEPO alone for 40 additional weeks . They were also given rHuG-CSF if they had relapses . A response was considered major if the hemoglobin ( Hb ) level was 115 g/L ( 11.5 g/dL ) or higher and minor Hb increase was 15 g/L ( 1.5 g/dL ) or more or if it remained stable without transfusion . Ten of 24 patients responded in arm A , and 0 of 26 responded in arm B ( P = .01 ) . Eight patients in arm A continued rHuEPO therapy alone , and 6 had relapses . Responses were always restored when rHuG-CSF was reintroduced . Mean direct costs per patient were 26,723 euros ( arm A ) and 8,746 euros ( arm B ) . Quality of life was assessed with a Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) scale . Similar percentages of patients from both arms showed significant clinical improvement . rHuEPO plus rHuG-CSF led to responses in 41.7 % of MDS patients . This treatment was expensive . No effect on quality of life was demonstrated", "A recent study in dogs suggested that erythropoietin ( EPO ) not only promotes the synthesis of increased numbers of reticulated platelets but that these newly produced platelets are hyperreactive compared with controls . Because of the increasing use of EPO in the perioperative setting , we characterized the effects of EPO on platelet reactivity in healthy human volunteers . In a r and omized , controlled trial , we studied the effects of EPO on platelet reactivity , thrombopoiesis , and endothelial activation in circumstances similar to those of autologous blood donation . Thirty healthy male volunteers received placebo or EPO ( 100 or 500 U/kg of body weight given intravenously ) three times a week for 2 weeks and underwent phlebotomy on days 8 and 15 . Thrombin receptor-activating peptide induced expression of P-selectin , and CD63 increased 2- to 3-fold during EPO treatment . The enhanced platelet reactivity was also reflected by a 50 % increase in soluble P-selectin in plasma . Plasma E-selectin levels increased in a dose-dependent fashion by more than 100 % during EPO treatment , indicating substantial activation of endothelial cells . A 10 % to 20 % increase in platelet counts was observed in both EPO groups on day 5 . In the placebo group , platelets increased only several days after the first phlebotomy . The increase in platelet counts was not reflected by changes in the amounts of reticulated platelets or circulating progenitor cells . In summary , we found that EPO markedly enhances endothelial activation and platelet reactivity , which may adversely affect patients at cardiovascular risk . However , the increased platelet reactivity could be exploited in patients with platelet dysfunction . ( Blood . 2000;95:2983 - 2989", "Background : Cervical cancer , in women , is the second most common cancer world wide , next to breast cancer . During the treatment of carcinoma cervix , anemia is selectively frequent and its origin is complex combining hemorrhage , iron deprivation , inflammatory reactions and infection . The objective of this study is to evaluate the role of epoetin in correction of anemia and on treatment outcomes in patients with advanced cervical cancer receiving concurrent chemoradiotherapy . Results : A total of 120 patients were enrolled in the study of which 60 patients were r and omized to receive epoetin beta in the treatment arm and 60 patients were in control arm where epoetin beta was not given . Total two and three patients absconded during treatment from treatment and control arm respectively ; therefore total evaluable patients were 115 . Mean Hb at baseline in the control arm was 10.70 + /- 0.62 g/dl and 10.45 + /- 0.43 g/dl in the treatment arm ( p = NS ) . At the end of treatment mean Hb increased by 1.55 g/dl in patients receiving epoetin beta ( p blood transfusion in patients receiving epoetin beta ( p energy level , activity level and overall quality of life in the treatment arm ( p overall survival ( p > 0.05 ) , or disease free survival ( p > 0.05 ) between the two study arms . Adverse events were well matched between the two study arms . No Thromboembolic events associated with epoetin beta was observed in our study . Material and methods : Total 120 , stage IIB to IIIB cervical cancer patients , aged 18 - 70 years with 9.50 - 12.50 g/dl baseline Hb value who were to receive radiotherapy together with cisplatin were r and omized to receive either epoetin beta 10,000 IU thrice weekly and oral iron starting 10 - 15 days before their 5-week course of whole pelvic irradiation and weekly cisplatin ( treatment arm ) or st and ard supportive care ( control arm ) , where epoetin beta was not given . Blood transfusion was given in patients of both the arms if hemoglobin was = 10 g/dl . Conclusions : Treatment with epoetin beta safely and effectively corrects anemia in patients with advanced cervical cancer receiving chemoradiotherapy and is not associated with adverse effects on response rate , overall survival , disease free survival and chemoradiotherapy related acute and late toxicities", "Summary . This phase 3 , r and omized , double‐blind , placebo‐controlled study was design ed to evaluate the efficacy and safety of darbepoetin alfa in anaemic patients with lymphoproliferative malignancies . Patients ( n = 344 ) with lymphoma or myeloma received darbepoetin alfa 2·25 μg/kg or placebo s.c . , once weekly for 12 weeks . The percentage of patients achieving a haemoglobin response was significantly higher in the darbepoetin alfa group ( 60 % ) than in the placebo group ( 18 % ) ( P increased responsiveness was observed in patients with lower baseline erythropoietin levels . Darbepoetin alfa also result ed in higher mean changes in haemoglobin than placebo from baseline to the last value during the treatment phase ( 1·80 g/dl vs 0·19 g/dl ) and after 12 weeks of treatment ( 2·66 g/dl vs 0·69 g/dl ) . A significantly lower percentage of patients in the darbepoetin alfa group received red blood cell transfusions than in the placebo group ( P efficacy of darbepoetin alfa was consistent for patients with lymphoma or myeloma . Improvements in quality of life were also observed with darbepoetin alfa . The overall safety profile of darbepoetin alfa was consistent with that expected for this patient population . Darbepoetin alfa significantly increased haemoglobin and reduced red blood cell transfusions in patients with lymphoproliferative malignancies receiving chemotherapy ", "Trials of anemia correction in chronic kidney disease have found either no benefit or detrimental outcomes of higher targets . We did a secondary analysis of patients with chronic kidney disease enrolled in the Correction of Hemoglobin in the Outcomes in Renal Insufficiency trial to measure the potential for competing benefit and harm from achieved hemoglobin and epoetin dose trials . In the 4 month analysis , significantly more patients in the high-hemoglobin compared to the low-hemoglobin arm were unable to achieve target hemoglobin and required high-dose epoetin-alpha . In unadjusted analyses , the inability to achieve a target hemoglobin and high-dose epoetin-alpha were each significantly associated with increased risk of a primary endpoint ( death , myocardial infa rct ion , congestive heart failure or stroke ) . In adjusted models , high-dose epoetin-alpha was associated with a significant increased hazard of a primary endpoint but the risk associated with r and omization to the high hemoglobin arm did not suggest a possible mediating effect of higher target via dose . Similar results were seen in the 9 month analysis . Our study demonstrates that patients achieving their target had better outcomes than those who did not ; and among subjects who achieved their r and omized target , no increased risk associated with the higher hemoglobin goal was detected . Prospect i ve studies are needed to confirm this relationship and determine safe dosing algorithms for patients unable to achieve target hemoglobin", "BACKGROUND Anaemia is associated with poor cancer control , particularly in patients undergoing radiotherapy . We investigated whether anaemia correction with epoetin beta could improve outcome of curative radiotherapy among patients with head and neck cancer . METHODS We did a multicentre , double-blind , r and omised , placebo-controlled trial in 351 patients ( haemoglobin curative radiotherapy at 60 Gy for completely ( R0 ) and histologically incomplete ( R1 ) resected disease , or 70 Gy for macroscopically incompletely resected ( R2 ) advanced disease ( T3 , T4 , or nodal involvement ) or for primary definitive treatment . All patients were assigned to subcutaneous placebo ( n=171 ) or epoetin beta 300 IU/kg ( n=180 ) three times weekly , from 10 - 14 days before and continuing throughout radiotherapy . The primary endpoint was locoregional progression-free survival . We assessed also time to locoregional progression and survival . Analysis was by intention to treat . FINDINGS 148 ( 82 % ) patients given epoetin beta achieved haemoglobin concentrations higher than 140 g/L ( women ) or 150 g/L ( men ) compared with 26 ( 15 % ) given placebo . However , locoregional progression-free survival was poorer with epoetin beta than with placebo ( adjusted relative risk 1.62 [ 95 % CI 1.22 - 2.14 ] ; p=0.0008 ) . For locoregional progression the relative risk was 1.69 ( 1.16 - 2.47 , p=0.007 ) and for survival was 1.39 ( 1.05 - 1.84 , p=0.02 ) . INTERPRETATION Epoetin beta corrects anaemia but does not improve cancer control or survival . Disease control might even be impaired . Patients receiving curative cancer treatment and given erythropoietin should be studied in carefully controlled trials", "Anaemia is common in patients receiving chemotherapy , causing symptoms that have a major impact on quality of life ( QoL ) . Epoetin beta rapidly increases haemoglobin ( Hb ) levels and improves QoL in anaemic patients with a variety of tumours . This was a r and omized , double-blind , parallel-group , dose-finding study assessing the efficacy and safety of once-weekly epoetin beta in patients with solid tumours receiving chemotherapy . Adult patients with anaemia ( Hb to receive epoetin beta 30,000 IU or 20,000 IU once weekly for 12 weeks . All patients received oral iron supplementation . Haemoglobin levels , transfusion need and QoL [ Functional Assessment of Cancer Therapy-fatigue ( FACT-F ) subscale score ] were assessed at regular intervals . Fifty patients were r and omized ; 30 patients received epoetin beta 30,000 IU once weekly and 20 received 20,000 IU once weekly . Mean ( + /- SD ) increase in Hb from baseline to week 12 was 1.75 + /- 2.15 g/dL in the 30,000 IU group ( P = 0.008 vs. baseline ) and 1.04 + /- 1.75 g/dL in the 20,000 IU group ( non-significant ) . Haemoglobin response ( increase in Hb > or=2 g/dL from baseline ) was observed in 78.3 % of patients receiving epoetin beta 30,000 IU and 66.7 % receiving epoetin beta 20,000 IU . Improvements in FACT-F subscale score were significantly ( P Hb level . Transfusion use was low during the study in both groups . Both epoetin beta regiments were well tolerated and there were no dose-dependent adverse events . Epoetin beta 30,000 IU once weekly is an effective and well-tolerated treatment of anaemia in patients with solid tumours", "Introduction : This study evaluated the safety/efficacy of once-weekly ( QW ) epoetin alfa measured by quality of life ( QOL ) , hemoglobin ( Hb ) , transfusion incidence , tumor response , and survival in patients with chemotherapy-naïve , advanced non-small cell lung cancer ( NSCLC ) . Methods : Stage IIIB/IV NSCLC patients with Hb ≥11 to to subcutaneously receive 40,000 U of epoetin alfa QW at chemotherapy initiation ( immediate ) or no epoetin alfa unless Hb decreased to ≤10 g/dl ( delayed ) . The primary efficacy variable was change in QOL for immediate versus delayed intervention . Target accrual was 320 patients . Results : The study was terminated early because of slow accrual ; of 216 patients enrolled , 211 were evaluable for efficacy . Hb was maintained in the immediate group , but it decreased in the delayed group ( 12.9 versus 11.6 g/dl final values , respectively ) . Numerically , fewer immediate patients required transfusions versus delayed patients . Mean QOL scores , modestly declining in both groups from baseline to final measurement , were not significantly different between groups . Tumor response and median overall survival were similar between groups . Epoetin alfa was well tolerated , with a similar thrombovascular event rate between groups . Conclusion : Epoetin alfa in subcutaneous doses of 40,000 U QW , given immediately at chemotherapy initiation for advanced NSCLC , was well tolerated , and it effectively maintained Hb , leading to a reduced transfusion incidence versus delayed epoetin alfa . Overall QOL scores were higher than typical in this population , decreasing slightly during treatment in both groups . Overall survival was similar between groups , with no evidence of a negative effect by early epoetin alfa intervention", "This r and omized , controlled trial evaluated the effect of darbepoetin alfa on hospitalization days , transfusion requirements , hemoglobin levels , and fatigue in patients with anemia of cancer ( AOC ) . Eligible patients were anemic ( hemoglobin or=18 years old , and had not received chemotherapy or radiotherapy within 4 weeks of study screening . Patients were r and omized 4:1 to receive darbepoetin alfa , 3.0 microg/kg every 2 weeks ( Q2W ) ( n = 226 ) , or observation only for 12 weeks ( n = 59 ) , followed by an optional 9 weeks of darbepoetin alfa , 3.0 microg/kg Q2W . Endpoints were compared between the two treatment arms at week 13 . A planned interim analysis indicated that assumptions regarding hospitalization in the study design were incorrect , so the study was terminated early . Therefore , results for the primary endpoint should be interpreted cautiously . The hospitalization rate was similar ( 0.5 days ) for both the darbepoetin alfa and observation groups ( p = .73 ) . Transfusion incidence ( weeks 5 - 12 ) was significantly lower for darbepoetin alfa patients ( 8 % ) than for observation patients ( 22 % ) ( p = .0092 ) . By week 13 , hemoglobin increased by 2.1 g/dl in patients receiving darbepoetin alfa , compared with 0.1 g/dl in the observation group p Hemoglobin improvements were paralleled by an increase in Functional Assessment of Cancer Therapy-Fatigue score ( mean change in score at week 13 : darbepoetin alfa , 6.0 ; observation , 2.2 ; p Darbepoetin alfa Q2W can significantly improve hemoglobin levels and reduce transfusion requirements in patients with AOC , result ing in significant improvements in health-related quality of life", "8064 Background : Darbepoetin alfa ( DA , Aranesp ® ) administered Q3W is effective for the treatment of CIA ( Kotasek et al , 2003 ) . NCCN guidelines recommend initiating erythropoietic therapy when hemoglobin ( Hb ) is DA to maintain Hb ≥ 10 g/dL in mildly anemic pts ( early intervention ) and pts who become moderately to severely anemic before treatment ( late intervention ) . METHODS Pts with baseline Hb ≥ 10.5 and ≤ 12 g/dL were r and omized 1:1 to early ( DA 300 mcg Q3W ) or late intervention ( treated if Hb ≤ 10 g/dL with DA 300 mcg Q3W ) groups for up to 23 weeks . The primary endpoint was the percentage of pts in each group with a Hb drop below 10 g/dL. Patient-reported outcomes included the FACT-Fatigue subscale . Proportion endpoints were calculated using Kaplan-Meier ( KM ) methods . RESULTS The study is fully enrolled with 204 pts . Data through week 17 for 201 evaluable pts ( 99 early and 102 late ) were analyzed . Mean ( SD ) baseline Hb for early pts was 11.1 ( 0.7 ) g/dL and 11.2 ( 0.6 ) g/dL for late pts . There was a significant ( P the K-M proportion ( 95 % CL ) of pts with a Hb drop maintained average Hb within the NCCN target range while late pts required DA after a median ( 95 % CL ) of 4.5 ( 3 , 6 ) weeks after r and omization . Thus , late pts achieved the NCCN target range after an average of 2 DA doses . The KM proportion ( 95 % CL ) for transfusions was lower for early pts ( 14 % ; 7 , 20 ) compared with late pts ( 22 % ; 13 , 30 ) . Early pts also performed better on the FACT-Fatigue . CONCLUSIONS These results suggest that DA 300 mcg Q3W is well tolerated and effective in achieving and maintaining Hb levels at a target level of 11 - 12 g/dL. In addition , early intervention results in fewer transfusions and greater symptom improvement compared with late intervention . The availability of a Q3W schedule for erythropoietic therapy can simplify the management of anemia and provide benefits for CIA pts and their caregivers . [ Table : see text ]", "PURPOSE This r and omized , double-blind , placebo-controlled clinical trial assessed the effects of epoetin alfa on transfusion requirements , hematopoietic parameters , quality of life ( QOL ) , and safety in anemic cancer patients receiving nonplatinum chemotherapy . The study also explored a possible relationship between increased hemoglobin and survival . PATIENTS AND METHODS Three hundred seventy-five patients with solid or nonmyeloid hematologic malignancies and hemoglobin levels or = 1.5 g/dL per cycle since starting chemotherapy , were r and omized 2:1 to epoetin alfa 150 to 300 IU/kg ( n = 251 ) or placebo ( n = 124 ) three times per week subcutaneously for 12 to 24 weeks . The primary end point was proportion of patients transfused ; secondary end points were change in hemoglobin and QOL . The protocol was amended before unblinding to prospect ively collect and assess survival data 12 months after the last patient completed the study . RESULTS Epoetin alfa , compared with placebo , significantly decreased transfusion requirements ( P = .0057 ) and increased hemoglobin ( P cancer- and anemia-specific QOL domains , including energy level , ability to do daily activities , and fatigue , was significantly ( P survival as an end point , Kaplan-Meier estimates showed a trend in overall survival favoring epoetin alfa ( P = .13 , log-rank test ) , and Cox regression analysis showed an estimated hazards ratio of 1.309 ( P = .052 ) favoring epoetin alfa . Adverse events were comparable between groups . CONCLUSION Epoetin alfa safely and effectively ameliorates anemia and significantly improves QOL in cancer patients receiving nonplatinum chemotherapy . Encouraging results regarding increased survival warrant another trial design ed to confirm these findings", "PURPOSE A placebo-controlled , double-blind , r and omized , phase III study was conducted in patients with extensive-stage small-cell lung cancer receiving first-line platinum-containing chemotherapy to determine if increasing or maintaining hemoglobin concentration with darbepoetin alpha could increase patient survival . PATIENTS AND METHODS Darbepoetin alpha ( 300 microg ) or placebo was administered once per week for 4 weeks then every 3 weeks for up to six cycles of chemotherapy ( carboplatin plus etoposide or cisplatin plus etoposide ) plus 3 weeks after the last dose of chemotherapy . Patients with disease progression were observed until death or until all patients completed their end-of- study visit and 496 deaths had occurred . The two co primary end points were change in hemoglobin concentration from baseline to the end of the chemotherapy period and overall survival ; statistical testing of survival was done if change in hemoglobin was significant at P The study enrolled 600 patients . Patients ' hemoglobin levels dropped due to the myelosuppressive chemotherapy ; however , treatment with darbepoetin alpha maintained hemoglobin levels significantly higher than placebo ( P overall survival between the treatment groups ( hazard ratio [ HR ] , 0.93 ; 95 % CI , 0.78 to 1.11 ; P = .431 ) . As expected , darbepoetin alpha was associated with a higher incidence of thromboembolic events ( darbepoetin alpha , 9 % ; placebo , 5 % ) . The transfusion risk was lower in the darbepoetin versus placebo group ( HR , 0.40 ; 95 % CI , 0.29 to 0.55 ) . CONCLUSION The results of this study did not demonstrate improved survival after treatment with darbepoetin alpha ; however , they reinforce the benefit of erythropoiesis-stimulating agents in reducing transfusions and their neutral impact on survival in patients with chemotherapy-induced anemia", "ABSTRACT Objective : Darbepoetin alfa is effective in treating chemotherapy-induced anemia ( CIA ) . Administration of subcutaneous darbepoetin alfa every 3 weeks ( Q3W ) could simplify treatment through synchronization with common Q3W chemotherapy regimens . We report results from a multicenter , r and omized , double-blind , placebo-controlled , phase 3 trial evaluating the efficacy and safety of fixed-dose Q3W darbepoetin alfa in patients with a wide variety of tumor types who experienced CIA . Research design and methods : Patients aged ≥ 18 years with anemia ( hemoglobin to receive darbepoetin alfa 300 μg ( n = 193 ) or placebo ( n = 193 ) subcutaneously Q3W from weeks 1 to 13 in this 16-week study . Doses could be adjusted per prespecified rules . Main outcome measures : The primary endpoint was the proportion of patients who received ≥1 red blood cell ( RBC ) transfusion between week 5 and the end of the treatment period ( EOTP ) . The study also analyzed the proportions of patients achieving a hemoglobin concentration ≥11 g/dL and subsequently maintaining hemoglobin levels above 11 g/dL , and the change in hemoglobin concentration over time . Results : The proportion of patients requiring RBC transfusions between week 5 and EOTP was significantly lower in the darbepoetin alfa-treated group than in the placebo-treated group ( 24 vs. 41 % of patients , a 16.3 % difference , p arms in quality -of-life measures . Cardiovascular/thromboembolic adverse events were uncommon and were not associated with increases in hemoglobin levels . Study limitations suggest caution in the interpretation of these results : transfusions , the primary endpoint , were recommended but not required if hemoglobin concentrations were ≤8.0 g/dL , and protocol deviations ( primarily dosing errors ) occurred in approximately one-half of the patients in both treatment groups . Conclusions : In this study , fixed-dose Q3W darbepoetin alfa appeared to be well-tolerated and effective for the treatment of CIA . Trial registration : Clinical Trials.gov identifier : NCT00110955", "PURPOSE To determine whether the addition of recombinant human erythropoietin ( Epo ) could improve the outcomes of anemic patients receiving definitive radiotherapy for squamous cell carcinoma of the head and neck ( SCCHN ) . METHODS AND MATERIAL S Eligible patients had SCCHN , with a plan for continuous-course definitive radiotherapy ( 66 - 72 Gy ) with or without chemotherapy . Patients with Stage III or IV SCCHN were required to undergo concurrent chemoradiotherapy and /or accelerated fractionation radiotherapy . Preradiotherapy hemoglobin was required to be between 9.0 g/dL and 13.5 g/dL ( 12.5 g/dL for women ) . Patients r and omized to Epo received 40,000 U once weekly , starting 7 - 10 days before start of radiotherapy . RESULTS A total of 148 patients were enrolled ; 141 were evaluable . Median pretreatment hemoglobin was 12.1 g/dL. Hemoglobin levels at 4 weeks rose by an average of 1.66 g/dL in the Epo arm , compared with an average 0.24 g/dL decrease in the control arm ( p = 0.0001 ) . Median follow-up was 2.5 years ( 3.1 years for surviving patients ) . There was no statistically significant difference in the primary endpoint of local-regional failure ( LRF ) rate between the treatment arms . The 3-year LRF rate was 36 % for control and 44 % for Epo ( p = 0.56 ) . There were also no significant differences in local-regional progression-free survival ( LRPFS ) , patterns of failure , overall survival , or toxicity . The 3-year LRPFS rate was 52 % for control and 47 % for Epo . The overall survival rate was 57 % and 56 % , respectively . CONCLUSIONS The addition of Epo to definitive radiotherapy for SCCHN did not improve outcomes . The study was not specifically design ed to detect a potential negative association between Epo and tumor progression/survival", "The optimal hemoglobin concentration at which to initiate erythropoietic therapy for chemotherapy-induced anemia ( CIA ) is not well defined . This r and omized , open-label , multicenter study evaluated the ability of darbepoetin alfa ( 300 microg every 3 weeks ) to maintain hemoglobin levels > or = 10 g/dl in patients with CIA ( hemoglobin > or = 10.5 g/dl and to an immediate-intervention group ( received darbepoetin alfa immediately ) or observation group ( received darbepoetin alfa if hemoglobin fell to 201 evaluable patients , there was a significant difference between the two groups in the Kaplan-Meier proportion of patients with a hemoglobin decrease to Sixty-four patients in the observation group received darbepoetin alfa ( delayed-intervention subgroup ) . The Kaplan-Meier proportion of patients who received transfusions was lower in the immediate-intervention group than in the delayed-intervention subgroup ( 14 % versus 31 % for the test period ; 17 % versus 36 % over the whole study ) . The target hemoglobin level ( > or = 11 g/dl ) was achieved by a higher percentage of patients ( crude percentage ) in less time in the immediate-intervention group ( 94 % in 2 weeks ) than in the delayed-intervention subgroup ( 73 % in 6 weeks ) ; hemoglobin endpoints for the delayed-intervention subgroup were calculated from recalibrated study week 1 ( the date patients first received darbepoetin alfa ) . For both groups , a higher mean change in hemoglobin from baseline led to a greater improvement in Functional Assessment of Cancer Therapy-Fatigue scores . In conclusion , immediate intervention result ed in a significantly lower proportion of patients who experienced a decline in hemoglobin , lower requirement for transfusions , and greater proportion of patients achieving and maintaining the target hemoglobin level", "Abstract . Objective : To compare the pharmacokinetics , pharmacodynamics , and tolerance of epoetin alfa administered subcutaneously ( s.c . ) once weekly ( q.w . ) and three times weekly ( t.i.w . ) . Methods : An open-label , r and omized , parallel- design study was conducted in 36 healthy adults with hemoglobin ( Hb ) levels of 11.7–14.0 g/dl for women and 13.0–14.8 g/dl for men . Subjects were r and omized to epoetin alfa 150 IU/kg s.c . t.i.w . or 40,000 IU s.c . q.w . for 4 weeks . Serum erythropoietin concentrations were measured using a vali date d enzyme-linked immunosorbent assay ( ELISA ) . Pharmacokinetic parameters [ peak serum concentration ( Cmax ) , mean predose trough concentration ( Cmin ) , time to Cmax ( tmax ) , clearance after s.c . administration ( CL/F ) , area under the plasma concentration – time curve ( AUC ) , and terminal elimination half-life ( t1/2 ) ] were calculated using model-independent methods . Mean changes from baseline and AUC of percentage reticulocytes , Hb , and total red blood cell ( RBC ) concentrations over the 1-month study period were calculated . Results : The Cmax values for serum epoetin alfa q.w . were six times and AUC(0–168 ) values three times that of the t.i.w . regimen . Time profiles of changes in percentage reticulocytes , Hb , and total RBC over 1 month were similar between regimens . The rate of increase in Hb was similar for the two groups , and both groups exhibited a 3.1-g/dl increase in mean Hb levels from baseline through day 29 . Changes in ferritin levels were generally similar between groups and reflected expected use of iron stores for Hb production . Epoetin alfa administered t.i.w . or q.w . was well tolerated and no serious adverse events occurred . Conclusion : The pharmacodynamic responses were equivalent between groups despite expected differences in total erythropoietin exposure . These results indicate that the epoetin alfa 150 IU/kg t.i.w . and 40,000 IU q.w . regimens can be considered clinical ly equivalent", "BACKGROUND Erythropoietin corrects and prevents anemia and decreases the need for red blood cell ( RBC ) transfusions ; its impact on quality of life ( QOL ) of cancer patients receiving chemotherapy is not clear . PATIENTS AND METHODS 399 patients with solid tumors and Hb level of to receive or not 10,000 IU epoetin-alpha thrice weekly . QOL was measured by the Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) scale and various subscales at baseline , at two months and at the end of the study . RESULTS Changes in the average QOL scores were similar in the two groups . The improvement in Hb levels was significantly higher for the epoetin-alpha group , with a decrease in transfusion requirements compared to the control group . CONCLUSION Epoetin-alpha does not improve QOL of patients with solid tumors receiving chemotherapy as assessed using FACT-An scale and various subscales , despite improving Hb levels and reducing transfusion requirements", "Recombinant human erythropoietin ( r-HuEPO ) was administered in two phases to 12 patients with chronic renal insufficiency ( creatinine clearances of 0.17–0.51 ml/second [ 10–30 ml/minute ] ) and uremic anemia . In addition to the routine tests done as part of a multicenter clinical trial , our patients had serial red cell mass measurements , quantitation of bone marrow stem cells , and marrow cytogenetic analysis . During the first eight weeks ( acute phase ) , an equal number of patients was r and omized to placebo or one of three doses of r-HuEPO ( 50 , 100 or 150 unit/kg intravenously three times weekly ) . All three patients receiving 150 unit/kg responded by increasing their packed cell volume ( PCV ) to the normal range within eight weeks . There were lesser responses in PCV at the two lower doses of r-HuEPO and no response in the placebo group . The 51Cr red cell mass also increased significantly in a dose-related manner in patients receiving r-HuEPO but did not change in the placebo group . Marrow studies revealed increases in erythroid , megakaryocyte , and granulocyte-monocyte progenitor cells in those patients on r-HuEPO , but no mutagenic effects were seen . Subsequently , ten patients received open label r-HuEPO . During this maintenance phase , all ten achieved or maintained a normal PCV . Several adverse events occurred , but none were definitely linked to r-HuEPO . Recombinant human erythropoietin is an effective and potent treatment of anemia caused by renal failure", "PURPOSE This r and omized , double-blind , placebo-controlled trial ( N93 - 004 ) evaluated the effects of epoetin alfa on tumor response to chemotherapy and survival in patients with small-cell lung cancer ( SCLC ) . PATIENTS AND METHODS Adult patients with hemoglobin received epoetin alfa 150 U/kg or placebo subcutaneously 3 times weekly until 3 weeks after completion of chemotherapy . Survival was assessed for 3 years . The primary end point was the proportion of patients with complete or partial response after three chemotherapy cycles . RESULTS The trial was terminated prematurely after 224 of a projected 400 patients were accrued . Baseline characteristics were similar between groups . Epoetin alfa and placebo patients ( n = 109 and n = 115 , respectively ) had mean baseline hemoglobin of 12.8 g/dL and 13.0 g/dL , respectively . Overall tumor response was similar between the epoetin alfa and placebo groups after three chemotherapy cycles ( 72 % and 67 % , respectively ; 95 % CI of difference , -6 % to 18 % ) and after completion of chemotherapy ( 60 % and 56 % , respectively ; 95 % CI of difference , -9 % to 17 % ) . Epoetin alfa and placebo groups had similar median overall survival ( 10.5 and 10.4 months , respectively ) and overall mortality ( 91.7 % and 87.8 % , respectively ; hazard ratio , 1.172 ; 95 % CI , 0.887 to 1.549 ; P = .264 ) . Hemoglobin was maintained in the prechemotherapy range in epoetin alfa patients , but decreased substantially in placebo patients . Fewer epoetin alfa patients than placebo patients required transfusion . CONCLUSION These results suggest that in newly diagnosed patients with SCLC epoetin alfa does not affect tumor response to chemotherapy or survival . However , the early trial closure makes these conclusions preliminary", " Chemotherapy‐related anemia is prevalent among patients with hematologic malignancies . A r and omized , open‐label , multicenter trial of early versus late epoetin alfa in this population was conducted , focusing on quality of life ( QOL ) ", "One hundred twenty-one anemic , transfusion-dependent patients with multiple myeloma ( MM ) or low- grade non-Hodgkin 's lymphoma ( NHL ) were r and omly allocated to receive ( a ) recombinant human erythropoietin ( rhEPO ) 10,000 U/d subcutaneously 7 days a week ( fixed dose group ) ( n = 38 ) , or ( b ) rhEPO 2,000 U/d subcutaneously for 8 weeks followed by step-wise escalation of the rhEPO dose ( titration group ) ( n = 44 ) , or ( c ) no rhEPO therapy ( control group ) ( n = 39 ) . The total treatment period was 24 weeks . There were no differences between the three groups with regard to baseline clinical , demographic , or health status measures . The cumulative response frequency , defined as elimination of the transfusion need in combination with an increase in the hemoglobin concentration by > 20 g/L , was 60 % in both rhEPO treatment groups and 24 % in the control group ( P = .01 and .02 , respectively , log rank test ) . For patients in the titration group the response rate on the first dose level ( 2,000 U/d ) was only 14 % . Cox 's univariate regression analysis revealed that an inadequately low endogenous erythropoietin concentration in relation to the degree of anemia and a baseline platelet concentration > or = 100 x 10(9)/L were significant predictors for response to rhEPO therapy ( P Multivariate regression analysis showed that relative erythropoietin concentration was the most important factor and the platelet count had no additional influence on response . Treatment with rhEPO was well tolerated . We conclude that treatment with rhEPO may be indicated in anemic MM and NHL patients with a relative erythropoietin deficiency . An initial dose of 5,000 U/d subcutaneously may be recommended", "PURPOSE Previous trials have suggested a quality -of-life ( QOL ) improvement for anemic cancer patients treated with erythropoietin , but few used QOL as the primary outcome . We design ed a trial to investigate the effects of epoetin alfa therapy on the QOL of anemic patients with advanced non-small-cell carcinoma of the lung ( NSCLC ) . PATIENTS AND METHODS A multicenter , r and omized , double-blind , placebo-controlled trial was conducted . The proposed sample size was 300 patients . Eligible patients were required to have NSCLC unsuitable for curative therapy and baseline hemoglobin ( Hgb ) levels less than 121 g/L. Patients were assigned to 12 weekly injections of subcutaneous epoetin alpha or placebo , targeting Hgb levels between 120 and 140 g/L. The primary outcome was the difference in the change in Functional Assessment of Cancer Therapy-Anemia scores between baseline and 12 weeks . RESULTS Reports of thrombotic events in other epoetin trials prompted an unplanned safety analysis after 70 patients had been r and omly assigned ( 33 to the active arm and 37 to the placebo arm ) . This revealed a significant difference in the median survival in favor of the patients on the placebo arm of the trial ( 63 v 129 days ; hazard ratio , 1.84 ; P = .04 ) . The Steering Committee closed the trial . Patient numbers compromised the interpretation of the QOL analysis , but a positive Hgb response was noted with epoetin alfa treatment . CONCLUSION An unplanned safety analysis suggested decreased overall survival in patients with advanced NSCLC treated with epoetin alfa . Although infrequent , other similar reports highlight the need for ongoing trials evaluating erythropoietin receptor agonists to ensure that overall survival is monitored closely", "INTRODUCTION ADVANCED CANCER is frequently associated with significant anaemia which may be worsened by the administration of chemotherapy with myelotoxic agents such as methotrexate or nephrotoxic agents such as cisplatin . Although anaemia in cancer patients may be multifactorial in origin , it is often categorised as the anaemia of chronic disease ( ACD ) [ 1,2 ] . ACD is characterised by erythroid hypoplasia of the bone marrow , a modest decrease in red cell survival , decreased bone marrow reutilization of iron , and inappropriately low erythropoietin levels for the degree of anaemia [ 2 ] . Consistent with this A C D model , i napp rop r i a t e ly low se rum erythropoietin levels for the degree of anaemia have recently been documented in cancer patients [ 3 ] . The symptomato logy of anaemia may con t r ibu t e substantially to the overall lack of well-being that cancer patients frequently experience during their disease process . The t ransfusions often required for pal l ia t ion of these symptoms carry significant risks . There is an estimated 20 % probability of some associated adverse effect including fever , chills , rash , urticaria and exposure to hepatitis [ 4 ] . The scope of this problem is substantial when one considers that the annual transfusion estimate for this patient group in the U.S.A. alone is one million units of red blood cells/whole blood [ 5 ] . The observation that , at any given haemoglobin level , serum erythropoiet in levels tend to be lower in cancer patients than in iron deficiency patients [ 3 ] suggests that anaemia in cancer is at least partially due to a relative deficiency of e ry thropoie t in . In c o n j u n c t i o n with this observation , recent work demonstrating both the eft]caw and safety of recombinant human erythropoietin ( r-HuEPO ) in increasing haematocrit in anaemic patients with chronic renal failure [ 6,7 ] and in anaemic , zidovudine (AZT)-treated HIVinfected patients [ 8 ] offers the possibility that exogenous erythropoietin may also be an effective treatment for anaemia in cancer patients . To test this possibility , we conducted a series of double-blind , placebo-controlled trials using r-HuEPO in anaemic cancer patients in three different patient population s to examine the safety of r-HuEPO treatment , and its impact on haematocrit , t ransfusion requi rements and quality of life . The three populat ions were : pat ients receiving no chemotherapy , pa t i en t s rece iv ing cyclic n o n c i s p l a t i n c o n t a i n i n g chemothe rapy and pa t ients receiving cyclic c isp la t incontaining chemotherapy", "BACKGROUND The influence of two regimens of erythropoetin beta on haemoglobin level , quality of life ( QoL ) and side-effects in patients with gynaecological malignancies was assessed . PATIENTS AND METHODS A total of 119 patients during chemotherapy were r and omised to either st and ard therapy with 10,000 IU erythropoetin beta three times a week ( group A ) or 20,000 IU twice a week ( group B ) . Haemoglobin level and QoL were measured . Characteristics of the study population were analysed with descriptive statistical methods . Analysis of variance for repeated measurements was performed with haemoglobin level as dependent variable , and time and study arms as factors . RESULTS The rise in haemoglobin levels and QoL improvement were significant , without any difference between study arms . Adverse events were similar , except significantly more thromboembolic events in group B ( 0 vs. 8 events ; p = 0.003 ) . CONCLUSION Our results show similar improvements in haemoglobin level and QoL , but raise the question whether less frequent dosing regimes may result in increased rates of thromboembolic events", "BACKGROUND High doses of human recombinant erythropoietin ( rHuEPO ) to achieve hemoglobin levels greater than 13 g/dL in patients with chronic kidney disease appear to be associated with increased mortality . STUDY DESIGN We conducted logistic regression and survival analyses in a retrospective cohort of long-term hemodialysis patients to examine the hypothesis that the induced iron depletion with result ant relative thrombocytosis may be a possible contributor to the link between the high rHuEPO dose-associated hemoglobin level of 13 g/dL or greater and mortality . SETTING & PARTICIPANTS The national data base of a large dialysis organization ( DaVita ) with 40,787 long-term hemodialysis patients during July to December 2001 and their survival up to July 2004 were examined . PREDICTORS Hemoglobin level , platelet count , and administered rHuEPO dose during each calendar quarter . OUTCOMES & OTHER MEASUREMENTS Case-mix-adjusted 3-year all-cause mortality and measures of iron stores , including serum ferritin and iron saturation ratio . RESULTS Higher platelet count was associated with lower iron stores and greater prescribed rHuEPO dose . Compared with a hemoglobin level of 12 to 13 g/dL , a hemoglobin level of 13 g/dL or greater was associated with increased mortality in the presence of relative thrombocytosis , ie , platelet count of 300,000/microL or greater ( case-mix-adjusted death-rate ratio , 1.21 ; 95 % confidence limits , 1.02 to 1.44 ; P = 0.03 ) as opposed to the absence of relative thrombocytosis ( death-rate ratio , 1.04 ; 95 % confidence limits , 0.98 to 1.08 ; P = 0.1 ) . A prescribed rHuEPO dose greater than 20,000 U/wk was associated with a greater likelihood of iron depletion ( iron saturation ratio relative thrombocytosis ( case-mix-adjusted odds ratio , 2.53 ; 95 % confidence limits , 2.37 to 2.69 ; and 1.36 ; 95 % confidence limits , 1.30 to 1.42 , respectively ; P mortality during 3 years ( death-rate ratio , 1.59 ; 95 % confidence limits , 1.54 to 1.65 ; P rHuEPO doses to achieve hemoglobin levels of 13 g/dL or greater in long-term hemodialysis patients . R and omized trials are needed to test these observational associations", "BACKGROUND Patients with advanced cancer frequently experience clinical ly significant anemia , which is often exacerbated by myelosuppressive chemotherapy . Consistent with the anemia of chronic disease , studies have documented serum erythropoietin levels that are inappropriately low for the degree of anemia in cancer patients . Myelosuppressive chemotherapy impairs erythropoiesis , which may not fully recover between treatment cycles . Recombinant human erythropoietin ( rHuEPO ) has been used safely and effectively to treat anemia in AIDS patients receiving zidovudine ( AZT ) and in patients with chronic renal failure . PURPOSE This study was design ed to evaluate the clinical role of rHuEPO in reducing symptomatic anemia in patients with advanced cancer who were receiving myelosuppressive chemotherapy ( excluding cisplatin ) . METHODS We studied 153 anemic cancer patients receiving cyclic combination chemotherapy in a prospect i ve multicenter , double-blind , placebo-controlled trial . The patients were r and omly assigned to receive either rHuEPO ( 150 U/kg ) or placebo subcutaneously three times a week for a maximum of 12 weeks or until the hematocrit level increased to 38%-40 % . If the hematocrit reached this target level before 12 weeks , the rHuEPO dose could be reduced to maintain the hematocrit at that level for the duration of the study . Response to rHuEPO therapy was assessed by measuring changes in hematocrit level , transfusion requirements , and quality of life . Quality -of-life assessment was based on patients ' responses to question naires before and after the courses of therapy . RESULTS The increase in hematocrit in the rHuEPO-treated group compared with hematocrit in the placebo-treated group was statistically significant ( P = .0001 ) as measured by percentage point of change from baseline to final evaluation , by an increase in hematocrit level of six percentage points or more unrelated to transfusion , and by a rise in hematocrit level to 38 % or more unrelated to transfusion . There was a trend toward the reduction in mean units of blood transfused per patient during months 2 and 3 of therapy combined in rHuEPO-treated patients compared with placebo-treated patients ( 0.91 U versus 1.65 U ; P = .056 ) . In addition , rHuEPO-treated patients experienced a statistically significant improvement in energy level and ability to perform daily activities ( P toxic effects except for increased incidence of diaphoresis ( P diarrhea ( P = .05 ) in the rHuEPO-treated group . CONCLUSIONS We conclude that rHuEPO is safe and effective for reversing anemia related to advanced cancer or to chemotherapy for cancer", "PURPOSE To evaluate the effect of epoetin alfa on local disease-free survival ( DFS ) , overall survival ( OS ) , and cancer treatment-related anemia and fatigue in patients with head and neck cancer receiving radical radiotherapy with curative intent . PATIENTS AND METHODS Patients ( N = 301 ) with hemoglobin ( Hb ) less than 15 g/dL were r and omly assigned in a ratio of 1:1 to receive radiotherapy plus epoetin alfa ( 10,000 U subcutaneously [ SC ] three times weekly if baseline Hb was or = 12.5 g/dL ) or radiotherapy alone . Hb levels were monitored weekly . The primary end point was local DFS , defined as the time from r and om assignment to local disease recurrence or death . Secondary efficacy end points included OS , local tumor response , and local tumor control . Patients were followed at 1 , 4 , 8 , and 12 weeks postradiotherapy and annually for 5 years . Cancer treatment-related anemia and fatigue were evaluated with the Functional Assessment of Cancer Therapy-Anemia and Functional Assessment of Cancer Therapy-Head and Neck . Adverse events were recorded up to 12 weeks postradiotherapy . RESULTS Hb levels increased from baseline with epoetin alfa . The median duration of local DFS was not statistically different between groups ( observation , 35.42 months ; epoetin alfa , 31.47 months ; hazard ratio , 1.04 ; 95 % CI , 0.77 to 1.41 ) . Groups did not significantly differ in DFS , OS , tumor outcomes , or cancer treatment-related anemia or fatigue . No new or unexpected adverse events were observed . CONCLUSION Addition of epoetin alfa to radical radiotherapy did not affect survival , tumor outcomes , anemia , or fatigue positively or negatively in patients with head and neck cancer", "This study compared the effects of early intervention with st and ard use of epoetin alfa on haemoglobin ( Hb ) levels and transfusion requirements in cancer patients receiving chemotherapy . Patients with Hb>10 and were r and omised 1:1 to epoetin alfa ( 40,000 IU , subcutaneously , once weekly ) , initiated within 7d of the start of the first on- study chemotherapy cycle ( defined as early intervention ) versus epoetin alfa when Hb Increases in Hb values were significantly higher with early intervention compared to st and ard therapy from week 6 to 10 ( P percentage of patients receiving blood transfusions was similar in both groups , the amount of blood transfused was almost twice as high in the st and ard epoetin alfa group ( n.s . ) . Early intervention with epoetin alfa was well tolerated and overall survival did not differ significantly between groups . Initiation of epoetin alfa at the onset of chemotherapy and Hb Hb levels significantly versus st and ard therapy", "PURPOSE Recent reports suggest that cancer control may worsen if erythropoietin is administered . We investigated whether erythropoietin receptor expression on cancer cells may correlate with this unexpected finding . PATIENTS AND METHODS Cancer tissue from patients with advanced carcinoma of the head and neck ( T3 , T4 , or nodal involvement ) and scheduled for radiotherapy was assayed retrospectively for erythropoietin receptor expression by immunohistochemistry . Patients were anemic and r and omized to receive epoetin beta ( 300 U/kg ) or placebo under double-blind conditions , given three times weekly starting 10 to 14 days before and continuing throughout radiotherapy . We administered 60 Gy following complete resection or 64 Gy subsequent to microscopically incomplete resection ; 70 Gy were given following macroscopically incomplete resection or for definitive radiotherapy alone . We determined if the effect of epoetin beta on locoregional progression-free survival was correlated with the expression of erythropoietin receptors on cancer cells using a Cox proportional hazards regression model . RESULTS We studied 154 of 157 r and omly assigned patients ; 104 sample s were positive , and 50 were negative for receptor expression . Locoregional progression-free survival was substantially poorer if epoetin beta was administered to patients positive for receptor expression compared with placebo ( adjusted relative risk , 2.07 ; 95 % CI , 1.27 to 3.36 ; P outcome in receptor-negative patients ( adjusted relative risk , 0.94 ; 95 % CI , 0.47 to 1.90 ; P = .86 ) . The difference in treatment associated relative risks ( 2.07 v 0.94 ) was borderline statistically significant ( P = .08 ) . CONCLUSION Erythropoietin might adversely affect prognosis of head and neck cancer patients if cancer cells express erythropoietin receptors", "BACKGROUND Epoetin-alpha initiated once weekly , followed by once-every-3-weeks maintenance , was effective and well tolerated for chemotherapy-induced anemia . This study evaluated a starting dose of epoetin-alpha 120,000 U once every 3 weeks for chemotherapy-induced anemia using early and late initiation regimens . METHODS Patients with baseline hemoglobin 11.0 - 12.0 g/dL were r and omly assigned to early intervention with immediate epoetin-alpha ( n = 68 ) or to st and ard intervention with epoetin-alpha when hemoglobin decreased to A third group of patients with baseline hemoglobin epoetin-alpha was initiated immediately . The primary endpoint was mean proportion of hemoglobin values within the target range ( 11.0 - 13.0 g/dL ) among r and omized patients . RESULTS The mean proportion of hemoglobin values in range through week 16 was 60 % in each r and omized group . Mean hemoglobin by week showed similar increases over the study . Blood transfusions were administered in 9 % , 8 % , and 24 % of patients in the early , st and ard , and nonr and omized groups . Mean epoetin-alpha doses were similar between treatment groups . Dose reductions and withholds were more common in the early intervention group . Adverse events ( eg , diarrhea , fatigue , nausea ) were consistent with the safety profile for epoetin-alpha . Clinical ly relevant thrombotic vascular events ( regardless of relationship to study treatment ) were reported for 9 % , 12 % , and 12 % of patients in the early , st and ard , and nonr and omized groups . CONCLUSIONS Early and st and ard intervention with epoetin-alpha , administered once every 3 weeks , increased and maintained hemoglobin levels within 11.0 - 13.0 g/dL in patients with chemotherapy-induced anemia", "BACKGROUND Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease . Although darbepoetin alfa can effectively increase hemoglobin levels , its effect on clinical outcomes in these patients has not been adequately tested . METHODS In this study involving 4038 patients with diabetes , chronic kidney disease , and anemia , we r and omly assigned 2012 patients to darbepoetin alfa to achieve a hemoglobin level of approximately 13 g per deciliter and 2026 patients to placebo , with rescue darbepoetin alfa when the hemoglobin level was less than 9.0 g per deciliter . The primary end points were the composite outcomes of death or a cardiovascular event ( nonfatal myocardial infa rct ion , congestive heart failure , stroke , or hospitalization for myocardial ischemia ) and of death or end-stage renal disease . RESULTS Death or a cardiovascular event occurred in 632 patients assigned to darbepoetin alfa and 602 patients assigned to placebo ( hazard ratio for darbepoetin alfa vs. placebo , 1.05 ; 95 % confidence interval [ CI ] , 0.94 to 1.17 ; P=0.41 ) . Death or end-stage renal disease occurred in 652 patients assigned to darbepoetin alfa and 618 patients assigned to placebo ( hazard ratio , 1.06 ; 95 % CI , 0.95 to 1.19 ; P=0.29 ) . Fatal or nonfatal stroke occurred in 101 patients assigned to darbepoetin alfa and 53 patients assigned to placebo ( hazard ratio , 1.92 ; 95 % CI , 1.38 to 2.68 ; P patient-reported fatigue in the darbepoetin alfa group as compared with the placebo group . CONCLUSIONS The use of darbepoetin alfa in patients with diabetes , chronic kidney disease , and moderate anemia who were not undergoing dialysis did not reduce the risk of either of the two primary composite outcomes ( either death or a cardiovascular event or death or a renal event ) and was associated with an increased risk of stroke . For many persons involved in clinical decision making , this risk will outweigh the potential benefits . ( Clinical Trials.gov number , NCT00093015 .", "PURPOSE The concomitant use of intravenous ( IV ) iron as a supplement to erythropoiesis-stimulating agents in patients with chemotherapy-induced anemia is controversial . This study was design ed to evaluate the efficacy and safety of darbepoetin alpha given with IV iron versus with local st and ard practice ( oral iron or no iron ) . PATIENTS AND METHODS In this multicenter , r and omized , open-label , phase III study , 396 patients with nonmyeloid malignancies and hemoglobin ( Hb ) less than 11 g/dL received darbepoetin alpha 500 microg with ( n = 200 ) or without ( n = 196 ) IV iron once every 3 weeks ( Q3W ) for 16 weeks . RESULTS The hematopoietic response rate ( proportion of patients achieving Hb > or= 12 g/dL or Hb increase of > or= 2 g/dL from baseline ) was significantly higher in the IV iron group : 86 % versus 73 % in the st and ard practice group ( difference of 13 % [ 95 % CI , 3 % to 23 % ] ; P = .011 ) . Fewer RBC transfusions ( week 5 to the end of the treatment period ) occurred in the IV iron group : 9 % versus 20 % in the st and ard practice group ( difference of -11 % [ 95 % CI , -18 % to -3 % ] ; P = .005 ) . Both treatments were well tolerated with no notable differences in adverse events . Serious adverse events related to iron occurred in 3 % of patients in the IV iron group and were mostly gastrointestinal in nature . CONCLUSION Addition of IV iron to darbepoetin alpha Q3W in patients with chemotherapy-induced anemia was well tolerated , result ing in an improved hematopoietic response rate and lower incidence of transfusions compared with darbepoetin alpha alone", "PURPOSE Unresponsiveness to erythropoiesis-stimulating agents , occurring in 30 % to 50 % of patients , is a major limitation to the treatment of chemotherapy-related anemia . We have prospect ively evaluated whether intravenous iron can increase the proportion of patients with chemotherapy-related anemia who respond to darbepoetin . PATIENTS AND METHODS Between December 2004 and February 2006 , 149 patients with lung , gynecologic , breast , and colorectal cancers and > or= 12 weeks of planned chemotherapy were enrolled from 33 institutions . Patients were required to have hemoglobin All patients received darbepoetin 150 microg subcutaneously once weekly for 12 weeks and were r and omly assigned to sodium ferric gluconate 125 mg intravenously ( IV ) weekly for the first 6 weeks ( n = 73 ) or no iron ( n = 76 ) . Primary end point of the study was the percentage of patients achieving hematopoietic response ( hemoglobin > or= 12 g/dL or > or= 2 g/dL increase ) . RESULTS Hematopoietic response by intention-to-treat analysis was 76.7 % ( 95%CI , 65.4 % to 85.8 % ) in the darbepoetin/iron group and 61.8 % ( 95%CI , 50.0 % to 72.7 % ) in the darbepoetin group ( P = .0495 ) . Among patients fulfilling eligibility criteria and having received at least four darbepoetin administrations , hematopoietic responses in the darbepoetin/iron group ( n = 53 ) and in the darbepoetin-only group ( n = 50 ) were 92.5 % ( 95 % CI , 81.8 % to 97.9 % ) and 70 % ( 95 % CI , 55.4 % to 82.1 % ) , respectively ( P = .0033 ) . Increase of hemoglobin during treatment period showed a time profile favoring darbepoetin/iron with statistically significant effect from week 5 on . The safety profile was comparable in the two arms . CONCLUSION In patients with chemotherapy-related anemia and no iron deficiency , IV iron supplementation significantly reduces treatment failures to darbepoetin without additional toxicity" ]	41188a1a-06ff-11f0-808a-c43d1ab1c353
Objectives To evaluate whether the application of mechanical bowel preparation ( MBP ) before colorectal surgery reduces the risk of developing infectious complications in children . Study design In this systematic review and meta‐ analysis , PubMed , Embase , and the Cochrane Library were systematic ally search ed to identify all articles comparing pediatric patients receiving MBP with pediatric patients not receiving MBP before colorectal surgery . Results are presented with weighted risk differences based on the number of events and sample size per study . Results Six original studies were included comparing MBP ( n = 810 ) and no MBP ( n = 1167 ) . The overall risk of developing infectious complications was 10.1 % in patients with MBP , compared with 9.1 % in patients without MBP , result ing in a nonsignificant risk difference of −0.03 % ( 95 % CI , −0.09 % to 0.03 % ) . Concerning the number of wound infections and anastomotic leaks , we found nonsignificant risk differences of −0.03 % ( 95 % CI , −0.08 % to 0.02 % ) and 0.01 % ( 95 % CI , −0.01 % to 0.02 % ) , respectively . Conclusion Based on the current literature , there is insufficient evidence to indicate that the use of MBP leads to a significant difference in the risk of developing infectious complications in pediatric colorectal surgery	[ "Objectives : Adult literature supports the elimination of mechanical bowel preparation ( MBP ) for elective colorectal surgical procedures . Prospect i ve data for the pediatric population regarding the utility of MBP are lacking . The primary aim of this study was to compare infectious complications , specifically anastomotic leak , intraabdominal abscess , and wound infection in patients who received MBP with those who did not . Methods : A r and omized pilot study comparing MBP with polyethylene glycol with no MBP was performed . Patients , 0 to 21 years old , undergoing elective colorectal surgery were eligible and r and omized within 4 age strata . Statistical analyses were performed using & khgr;2 or Fisher exact test for categorical data and t test or Wilcoxon 2- sample test for continuous data . Results : Forty-four patients were enrolled in the study from December 2010 to February 2013 , of which 24 ( 55 % ) received MBP and 20 ( 45 % ) did not . Two patients ( 5 % ) had anastomotic leak , 4 ( 9 % ) had intraabdominal infection , and 7 ( 16 % ) had wound infections . The rate of anastomotic leak , intraabdominal abscess , and wound infection did not differ between the 2 groups . Conclusions : MBP for elective colorectal surgery in children does not affect the incidence of infectious complications . A larger multiinstitutional study is necessary to vali date the results of this single-institution pilot study", "BACKGROUND Surgical site infections ( SSI ) are a common complication after colorectal surgery . An infection prevention bundle ( IPB ) was implemented to improve outcomes . STUDY DESIGN A st and ardized IPB that included the administration of oral antibiotics with a mechanical bowel preparation , preoperative shower with chlorhexidine , hair removal and skin preparation in holding , antibiotic wound irrigation , and a \" clean-closure \" protocol was implemented in January 2013 . Data from the American College of Surgeons NSQIP were analyzed at a single academic institution to compare pre-IPB and post-IPB SSI rates . In January 2014 , a prospect i ve data base was implemented to determine compliance with individual IPB elements and their effect on outcomes . RESULTS For the 24 months pre-IPB , the overall SSI rate was 19.7 % . During the 30 months after IPB implementation , the SSI rate decreased to 8.2 % ( p A subset of 307 patients was identified in both NSQIP and our prospect i ve compliance data bases . Elements of IPB associated with decreased SSI rates included preoperative shower with chlorhexidine ( 4.6 % vs 16.2 % ; p = 0.005 ) , oral antibiotics ( 3.4 % vs 15.4 % ; p full bowel preparation of both oral antibiotics and a mechanical bowel preparation had a 2.7 % SSI rate compared with 15.8 % for all others ( p fewer SSI ( adjusted odds ratio 0.2 ; 95 % CI 0.1 to 0.9 ; p = 0.006 ) . CONCLUSIONS Implementation of an IPB was successful in decreasing SSI rates in colorectal surgery patients . The combination of oral antibiotics with a mechanical bowel preparation was the strongest predictor of decreased SSI", "The role of preoperative bowel prep in the pediatric surgical population is uncertain . We performed a r and omized prospect i ve study to evaluate noninferiority between the presence or absence of a preoperative bowel prep in elective pediatric bowel surgery on postoperative outcomes . Patients aged three months to 18 years were recruited and r and omized to the bowel prep group or the no bowel prep group . Patients were evaluated in-hospital and at postoperative clinic visits . Thirty-two patients were recruited ; 18 in the bowel prep group and 14 in the no bowel prep group . There was no statistical difference ( P > 0.05 ) in complications between the groups . Complications were observed in five patients in each group ( 27.8 % and 35.7 % , respectively ) . In the bowel prep group , two ( 11.1 % ) had wound infection ( vs three , 21.4 % ) , 0 had an intra-abdominal abscess ( vs one , 7.1 % ) , one ( 5.6 % ) had sepsis ( vs one , 7.1 % ) , one ( 5.6 % ) had an anastomotic leak ( vs 0 ) , and three ( 16.7 % ) had a bowel obstruction ( vs one , 7.1 % ) . There were no extra-abdominal complications . There were no significant differences in complications between the two groups . Further research is warranted , but may require a multi-institutional trial to recruit sufficient numbers to make conclusions about the significance of the need for bowel prep", "PURPOSE It is well established through r and omized trials that oral antibiotics given with or without a mechanical bowel preparation ( MBP ) prior to colorectal procedures reduce complications , while MBP given alone provides no benefit . We aim ed to characterize trends surrounding bowel preparation in children and determine whether contemporary practice is evidence -based . METHODS Retrospective analysis of patients undergoing colorectal procedures at 42 children 's hospitals ( 1/2/2007 - 12/31/2011 ) was performed . Patients were analyzed for diagnosis , pre-admission status , and inpatient bowel preparation . Bowel preparation was considered evidence -based if oral antibiotics were utilized with or without a MBP . RESULTS 49 % of all patients were pre-admitted ( n=5,473 ) , and the most common diagnoses were anorectal malformations ( 55 % ) , inflammatory bowel disease ( 26 % ) , and Hirschsprung 's Disease ( 19 % ) . The most common preparation approaches were MBP alone ( 54.3 % ) , MBP+oral antibiotics ( 18.8 % ) , and oral antibiotics alone ( 4.2 % ) , although significant variation was found in hospital-specific rates for each approach ( MBP alone : 0 - 96.1 % , MBP+oral antibiotics : 0 - 83.6 % , orals alone : 0 - 91.6 % , p an evidence -based preparation ( range by hospital : 0 - 92.3 % , p children pre-admitted for elective colorectal procedures receive a bowel preparation proven to reduce infectious complications", "PURPOSE Despite rigorous data from adult literature demonstrating that oral antibiotics ( OA ) reduce infectious complications and mechanical bowel preparation ( MBP ) alone does not , MBP alone remains the preferred approach among pediatric surgeons . We aim ed to explore the nature of this discrepancy through a survey of the American Pediatric Surgical Association membership . METHODS Surgeons were queried for their choice of bowel preparation , factors influencing their practice , and their impression of the strength and relevance of the adult literature to pediatric practice . RESULTS Surgeons who used MBP alone ( 31 % ) cited a reduction in stool burden and infectious complications as important factors , whereas surgeons choosing not to use OA ( 70 % ) reported a lack of benefit in reducing infectious complications as the primary reason . Although 53 % of surgeons reported that evidence from adult literature was the most important influence , 73 % of surgeons reported there was poor evidence supporting the use of OA ( ±MBP ) , and only 25 % used a preparation supported by adult r and omized data . CONCLUSIONS Wide variation exists among pediatric surgeons in the perceived utility of MBP and OA . Although the majority of pediatric surgeons cited the adult literature as the strongest influence on their practice , this is not consistent with stated perceptions or practice", "BACKGROUND / PURPOSE Preoperative mechanical bowel preparation ( MBP ) for elective intestinal operations has been a long accepted practice . However , MBP is often unpleasant and time-consuming for patients , and clinical trials in adults have not shown improved outcomes . We conducted this pilot study to test whether omitting MBP before elective intestinal operations in infants and children would increase the risk of infectious or anastomotic complications . METHODS Retrospective review was performed of 143 patients who had an elective colon or distal small bowel procedure performed at our children 's hospital between 1990 and 2003 . RESULTS Thirty-three patients ( No PREP ) were managed by a single surgeon who routinely omitted MBP , whereas another 110 patients ( PREP ) were prepared with enemas , laxatives , or both . Both groups received 24 hours of preoperative dietary restriction to clear liquids and perioperative parenteral antibiotics . The No PREP group had one anastomotic leak and no wound infections , whereas the PREP group had 2 anastomotic leaks and 1 wound infection ( P = .58 ) . These results occurred despite greater duration of antibiotic therapy and incidence of delayed wound closures in the PREP group . CONCLUSION The results of this pilot study suggest that omitting MBP before elective intestinal operations in infants and children carries no increased risk of infectious or anastomotic complications . Eliminating MBP may reduce health care costs and inconvenience to patients . These findings warrant a large , prospect i ve , r and omized clinical trial to vali date our findings and to investigate further the necessity of MBP in the pediatric population", "BACKGROUND Guidelines regarding bowel preparation exist for the adult but not the pediatric population . Our aim was to evaluate the bowel preparation practice s , including antibiotic usage for elective colorectal operations in children . METHODS A survey was design ed and administered to a nationwide group of pediatric surgeons to ascertain current practice s of bowel preparation . RESULTS Four hundred ninety-three surveys were administered , and 136 physicians responded ( 28 % ) . Mechanical bowel preparation was used by 96 % of the respondents . Preoperative intravenous antibiotics were used by 99 % of respondents . The number of years in practice did not significantly affect the use of oral antibiotics ( P = .62 ) or the duration of intravenous antibiotics ( P = .78 ) . CONCLUSIONS There is a wide variation in bowel preparation practice s in children . A prospect i ve , r and omized trial would be helpful to identify the role of oral antibiotics and optimal duration of intravenous antibiotics in this population", "Introduction : Surgical site infection ( SSI ) is a potentially morbid and costly complication following major colorectal resection . In recent years , there has been growing attention placed on the accurate identification and monitoring of such surgical complications and their costs , measured in terms of increased morbidity to patients and increased financial costs to society . We hypothesize that incisional SSIs following elective colorectal resection are more frequent than is generally reported in the literature , that they can be predicated by measurable perioperative factors , and that they carry substantial morbidity and cost . Methods : Over a 2-year period at a university hospital , data on all elective colorectal resections performed by a single surgeon were retrospectively collected . The outcome of interest was a diagnosis of incisional SSI as defined by the Center of Disease Control and Prevention . Variables associated with infection , as identified in the literature or by experts , were collected and analyzed for their association with incisional SSI development in this patient cohort . Multivariate analysis by stepwise logistic regression was then performed on those variables associated with incisional SSI by univariate analysis to determine their prognostic significance . The incidence of SSI in this study was compared with the rates of incisional SSI in this patient population reported in the literature , predicted by a nationally based system monitoring nosocomial infection , and described in a prospect ively acquired intradepartmental surgical infection data base at our institution . Results : One hundred seventy-six patients undergoing elective colorectal resection were identified for evaluation . The mean patient age was 62 ± 1.2 years , and 54 % were men . Preoperative diagnoses included colorectal cancer ( 57 % ) , inflammatory bowel disease ( 20 % ) , diverticulitis ( 10 % ) , and benign polyp disease ( 5 % ) . SSIs were identified in 45 patients ( 26 % ) . Twenty-two ( 49 % ) SSIs were detected in the outpatient setting following discharge . Of all preoperative and perioperative variables measured , increasing patient body mass index and intraoperative hypotension independently predicted incisional SSI . Although we could not measure statistically increased length of hospital stay associated with SSI , a representative population of patients with SSI accumulated a mean of $ 6200/patient of home health expenses related to wound care . Our rates of SSI were substantially higher than that reported generally in the literature , predicted by the National Nosocomial Infection System , or described by our own institutional surgical infection data base . Conclusions : The incidence of incisional SSI in patients undergoing elective colorectal resection in our cohort was substantially higher than generally reported in the literature , the NNIS or predicted by an institutional surgical infection complication registry . Although some of these differences may be attributable to patient population differences , we believe these discrepancies highlight the potential limitations of systematic outcomes measurement tools which are independent of the primary clinical care team . Accurate surgical complication documentation by the primary clinical team is critical to identify the true frequency and etiology of surgical complications such as incisional SSI , to rationally approach their reduction and decrease their associated costs to patients and the health care system", "BACKGROUND The utility of mechanical bowel preparation ( MBP ) to minimize infectious complications in elective colorectal surgery is contentious . Though data is scarce in children , adult studies suggest a benefit to MBP when administered with oral antibiotics ( OAB ) . METHODS After IRB approval , the Pediatric Health Information System ( PHIS ) was queried for young children undergoing elective colon surgery from 2011 to 2014 . Patients were divided into : no bowel preparation ( Group 1 ) , MBP ( Group 2 ) , and MBP plus OAB ( Group 3 ) . Statistical significance was determined using univariate and multivariate analysis with GEE models accounting for clustering by hospital . RESULTS One thous and five hundred eighty-one patients met study criteria : 63.7 % in Group 1 , 27.1 % in Group 2 , and 9.2 % in Group 3 . Surgical complication rate was higher in Group 1 ( 23.3 % ) compared to Groups 2 and 3 ( 14.2 % and 15.5 % ; P However , median length of stay was shorter in Group 1 ( 4 , IQR 4days ) compared to Group 2 ( 5 , IQR 3 ) and Group 3 ( 6 , IQR 3 ) ( P 30-day readmission rates were similar . In multivariate analysis compared to patients in Group 1 , the odds of surgical complications were 0.72 ( 95 % CI 0.40 - 1.29 , P=0.28 ) with MBP alone ( Group 2 ) , 1.79 ( 95 % CI 1.28 - 2.52 , P=0.0008 ) with MBP+OAB ( Group 3 ) , and 1.13 ( 95 % CI 0.81 - 1.58 , P=0.46 ) for the aggregate Group 2 plus 3 . CONCLUSION Utilization of bowel preparation in children is variable across children 's hospitals nationally , and the benefit is unclear . Given the discrepancy with adult literature , a three-armed pediatric-specific r and omized controlled trial is warranted . LEVEL OF EVIDENCE Level III treatment study - retrospective comparative study" ]	41188a56-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Antibiotic prophylaxis is recommended in cardiac surgery . Current debate concerns the type of antibiotic(s ) , dosing and the duration of prophylaxis . METHODS Systematic review of r and omized controlled trials comparing one antibiotic regimen versus another in cardiac surgery . We search ed The Cochrane Library , PubMed , LILACS , conference proceedings and bibliographies . Two review ers independently extracted the data . The primary outcome was deep sternal wound infections ( DSWIs ) . Meta- analysis was performed using the Mantel-Haenszel fixed-effect method . Risk ratios ( RRs ) with 95 % confidence intervals ( 95 % CIs ) are reported . RESULTS Fifty-nine trials were included . There were no significant differences in DSWI or all other categories of surgical site infections ( SSIs ) for antibiotic prophylaxis with β-lactams comprising a Gram-negative spectrum of coverage versus prophylaxis targeting Gram-positive bacteria , but the former led to a significantly lower rate of post-operative pneumonia ( RR 0.68 , 95 % CI 0.51 - 0.90 ) and all-cause mortality ( RR 0.66 , 95 % CI 0.47 - 0.92 ) . In trials comparing different antibiotic regimens for different duration s , prophylaxis duration of ≤24 h post-operation led to higher rates of DSWI ( RR 1.83 , 95 % CI 1.25 - 2.66 ) , any sternal SSI , surgical interventions for SSI and endocarditis compared with longer duration prophylaxis . There was no advantage of regimens lasting > 48 h post-operation . In the comparison of glycopeptides versus β-lactams , an advantage of glycopeptides was observed when comparators were given for similar duration and for β-lactams when given for a longer duration than the glycopeptides . There was no significant advantage of high antibiotic dosing . CONCLUSIONS Evidence supports second- or third-generation cephalosporins for cardiac surgery prophylaxis and points at a possible advantage of prophylaxis prolongation up to 48 h post-operatively	[ "BACKGROUND Antimicrobial prophylaxis in cardiac surgery has been demonstrated to lower the incidence of surgical site infection ( SSI ) . Inappropriate antimicrobial prophylaxis , such as inappropriate selection of the antimicrobial agent or inappropriate dosing regimen , can increase the prevalence of antibiotic resistant strains , prolong hospital stay , cause adverse reactions , and negatively affect an institution 's pharmacy budget for antibiotics . In developing countries such as Jordan , where the role of clinical pharmacists is still in its primary stages , the first step in establishing an organized clinical pharmacy service is the evaluation of current practice to determine the need for improvement . OBJECTIVE To assess the degree of adherence to international guidelines for antimicrobial prophylaxis practice in cardiac surgery performed at Queen Alia Heart Institute ( QAHI ) in Amman , Jordan , as part of an attempt to determine opportunities for clinical pharmacist intervention . METHODS For a total of 236 patients who were admitted for cardiac surgery to QAHI - the only official referral hospital for cardiac patients in Jordan - between November 19 , 2006 , and January 22 , 2007 , the antimicrobial prophylaxis indication , choice , duration , dose , dosing interval , and timing appropriateness were assessed against 3 international guidelines using a pre-tested , structured clinical data collection form that was completed by 2 of the authors who work at QAHI . The study design was prospect i ve . All patients who were scheduled for surgery were monitored daily during their inpatient stay until discharge and then were tracked in the outpatient clinic for 2 months following surgery . Data regarding antimicrobial prophylaxis indication , choice , duration , dose , dosing interval , and timing appropriateness were collected during the patient 's inpatient stay ; data collection was performed periodically thereafter as data became available until the end of the 2-month follow-up . The 3 guidelines agreed that ( a ) antimicrobial prophylaxis should be given to all patients undergoing cardiac surgeries ; ( b ) the first- or second-generation cephalosporins ( cefazolin or cefuroxime ) are the antibiotics of choice , and vancomycin use is reserved for cases of allergy to beta-lactams or if presumed or known methicillin-resistant Staphylococcus aureus ( MRSA ) colonization is present ; ( c ) the timing of the first dose should be within 60 minutes prior to the skin incision ; and ( d ) the duration of antimicrobial prophylaxis should not be longer than 48 hours . RESULTS Adherence to all antimicrobial prophylaxis guidelines was not achieved for any study patients . For the 6 evaluated criteria , ( 1 ) indication : in 100 % of patients the appropriate decision was made to use antimicrobial prophylaxis in concordance with guidelines ; ( 2 ) choice : only 1.7 % of patients received the antibiotic of choice ; ( 3 ) duration : 39.4 % of patents received antimicrobial prophylaxis for a total duration of 48 hours or less in concordance with guidelines , and for 58.9 % of patients , duration was longer than recommended ; ( 4 ) dose : 27.9 % of patients received an appropriate dose ; ( 5 ) dosing interval : only 13.0 % of patients received an appropriate dosing interval , and none of the doses of antimicrobial prophylaxis used at induction of anesthesia was repeated in operations that lasted longer than the half-life of the antibiotic used ; and ( 6 ) timing : 99.1 % of patients received antimicrobial prophylaxis dose within 60 minutes prior to skin incision as recommended by guidelines , but 97.0 % of patients received an unnecessary midnight dose of intravenous antibiotic the night before surgery . CONCLUSION Study findings indicate that adherence to international guidelines for antimicrobial prophylaxis is far from optimal in QAHI , leading to the inappropriate administration of many antibiotics . Developing local hospital guidelines , as well as giving the clinical pharmacist a central role in the administration , monitoring , and intervention of antimicrobial prophylaxis may improve the current practice", "BACKGROUND Despite evidence supporting short antibiotic prophylaxis ( ABP ) , it is still common practice to continue ABP for more than 48 hours after coronary artery bypass graft ( CABG ) surgery . METHODS AND RESULTS To compare the effect of short ( prolonged ( > 48 hours ) ABP on surgical site infections ( SSIs ) and acquired antimicrobial resistance , we conducted an observational 4-year cohort study at a tertiary-care center . An experienced infection control nurse performed prospect i ve surveillance of 2641 patients undergoing CABG surgery . The main exposure was the duration of ABP , and main outcomes were the adjusted rate of SSI and the isolation of cephalosporin-resistant enterobacteriaceae and vancomycin-resistant enterococci ( acquired antibiotic resistance ) . Adjustment for confounding was performed by multivariable modeling . A total of 231 SSIs ( 8.7 % ) occurred after a median of 16 days , including 93 chest-wound infections ( 3.5 % ) and 13 deep-organ-space infections ( 0 . 5 % ) . After 1502 procedures using short ABP , 131 SSIs were recorded , compared with 100 SSIs after 1139 operations with prolonged ABP ( crude OR , 1.0 ; CI , 0.8 to 1.3 ) . After adjustment for possible confounding , prolonged ABP was not associated with a decreased risk of SSI ( adjusted OR , 1.2 ; CI , 0.8 to 1.6 ) and was correlated with an increased risk of acquired antibiotic resistance ( adjusted OR , 1.6 ; CI , 1.1 to 2.6 ) . CONCLUSIONS Our findings confirm that continuing ABP beyond 48 hours after CABG surgery is still widespread ; however , this practice is ineffective in reducing SSI , increases antimicrobial resistance , and should therefore be avoided", "A r and omized , prospect i ve study of the relative effectiveness of clindamycin versus cephalothin was performed in 263 adult patients having cardiac surgery from September , 1977 , to August , 1978 . There were no statistically significant differences in frequency of postoperative infections in these two antibiotic groups . Wound infection developed in 6.5 percent of the cephalothin group and 3.2 percent of the clindamycin group . Urinary tract infection developed in 5.6 percent of the clindamycin group and 2.1 percent of the cephalothin group . Four bacteremic episodes occurred in the clindamycin-treated patients , and one episode of bacteremia occurred in a cephalothin-treated patient . No cases of endocarditis occurred during the study . Clindamycin deserved consideration as an alternative prophylactic agent to cephalothin for cardiac surgery", "BACKGROUND The purpose of this study was to assess the value of tracheal aspirate as a predictor of pneumonia after coronary artery bypass grafting and to evaluate the efficacy of prolonged perioperative antibiotic prophylaxis . METHODS Tracheal aspirates of 500 patients undergoing coronary artery bypass grafting were taken immediately after intubation and analyzed for microorganisms by Gram stain and semiquantitative microbiologic cultures . All patients received 2 g ceftriaxone as a single-dose perioperative antibiotic prophylaxis before operation . Results of Gram stains were available before the patients were transferred to the intensive care unit . After the results were known , both groups of patients ( positive Gram stain , group 1 ; negative Gram stain , group 2 ) were r and omly assigned to either conventional antibiotic prophylaxis ( A ) , consisting of ceftriaxone 2 g on postoperative day 1 , or prolonged antibiotic prophylaxis ( B ) , with ticarcillin + clavulanic acid 3 x 5.2 g during 72 hours . RESULTS From 500 patients , 91 had a positive Gram stain whereas 409 had a negative one . The incidence of pneumonia was significantly higher in patients with preoperative positive tracheal aspirates ( 15.3 % ) than in patients with a negative one ( 3.6 % ; p rate of postoperative pneumonia , which was as high as 13 % in untreated positive patients versus 17 % in treated positive patients , and 2 % in untreated negative patients versus 4 % in treated patients . In patients who had pneumonia , there was a high correlation between the microorganisms found in preoperative aspirates and those observed when aspirates were repeated ( 100 % correlation in patients with conventional antibiotic prophylaxis and 87 % in those with prolonged prophylaxis ) . CONCLUSIONS Early postoperative pneumonia ( perioperative antibiotic prophylaxis has no efficacy in reducing the incidence of pulmonary infections", "OBJECTIVE To evaluate national practice for antibiotic prophylaxis in cardiac surgery with respect to the use of protocol s , agent selection and duration of administration . DESIGN , SETTING AND PARTICIPANTS Two point-prevalence surveys of intensive care units in 24 public and 27 private hospitals performing cardiac surgery in Australia , conducted in 2004 and 2008 , using a structured telephone question naire of the attending senior intensive care clinician in each unit . MAIN OUTCOME MEASURES Existence of a protocol in the unit for antibiotic prophylaxis , specific antibiotic agents used and their duration of administration . RESULTS Between 2004 and 2008 , reported protocol use increased from 58 % to 80 % ( P = 0.02 ) , while concordance with version 13 of the Australian Therapeutic guidelines : antibiotic for both choice of agent and timing ( duration of administration ) remained around 10 % . Use of multiple agents was common , as was continued antibiotic administration after completion of surgery . Over 4 years , the proportion of cardiac surgical units reporting vancomycin administration for routine valve surgery prophylaxis doubled to 62 % ( P duration of antibiotic administration deviating most from recommendations . Prophylactic vancomycin use appears to have increased substantially in recent years . Clinical implementation of recommended perioperative cardiac surgical antibiotic prophylaxis may not occur until supported by evidence from either a large prospect i ve r and omised study or st and ardised national surveillance of cardiac surgical site infection rates", "OBJECTIVE Cephalosporins , especially cefazolin , are widely used in the prevention of postoperative wound infections after cardiac operations . As more and more Staphylococcus aureus and Staphylococcus epidermidis strains are becoming resistant to cephalosporins and other antibiotics , alternative agents , such as glycopeptides , are often used as prophylaxis . We performed a multicenter double-blind r and omized controlled trial comparing teicoplanin , a glycopeptide antibiotic , with cefazolin . METHODS A total of 3027 adult patients undergoing elective coronary artery bypass grafting , valve operations , or both were r and omized to a single dose of teicoplanin ( 15 mg/kg ) or a 2-day course of cefazolin ( 2 g initial dose , followed by 1 g every 8 hours for 6 more doses ) . Patients were followed up for a total of 6 months postoperatively . The primary objective was to compare , between groups , the incidence of surgical infections up to 30 days postoperatively . Secondary objectives were incidence of other infections , other complications , and death . RESULTS A total of 3027 patients were r and omized to receive either teicoplanin ( n = 1518 ) or cefazolin ( n = 1509 ) . Thirty days postoperatively , there was a trend to more deep sternotomy wound infections in the teicoplanin group ( 31 vs 18 , P = . 087 ) , which became significant by 6 months ( 36 vs 19 , P = .032 ) . One hundred percent of the gram-positive strains infecting patients were susceptible to teicoplanin , whereas 8.3 % were resistant to cefazolin . Pneumonia and urinary tract infections were more common in the teicoplanin group . Deep wound infections of the leg were more common in the cefazolin group . CONCLUSIONS Cefazolin was more effective prophylaxis than teicoplanin against postoperative wound infections after elective cardiac operations . Infection rates were low with either treatment", "Purpose Major heart surgery ( MHS ) patients are a particularly high-risk population for nosocomial infections . Our objective was to identify risk factors for ventilator-associated pneumonia ( VAP ) in patients undergoing MHS . Methods Prospect i ve study including 1,844 patients operated from 2003 to 2006 . Results Overall 106 patients ( 140 episodes ) developed one or more episodes of VAP ( 5.7 % , 22.2 episodes per 1,000 days of mechanical ventilation ) . VAP incidence was 45.9 % in those patients requiring more than 48 h of MV . Enterobacteriaceae ( 32.8 ) , Pseudomonas aeruginosa ( 28.6 % ) and Staphylococcus aureus ( 27.1 % , of which 65.8 % were methicillin resistant ) were the principal microorganisms causing VAP . The independent risk factors for VAP were : age > 70 , perioperative transfusions , days of mechanical ventilation , reintubation , previous cardiac surgery , emergent surgery and intraoperative inotropic support . Median length of stay in the ICU for patients who developed VAP or not was , respectively , 25.5 versus 3 days ( P mortality was , respectively , 45.7 versus 2.8 % in both population s ( P predictive preoperative score with a sensitivity of 93 % and a specificity of 40 % . Conclusions VAP is common in patients undergoing MHS that require more than 48 h of MV . In that “ high-risk ” population , innovative preventive measures should be developed and applied", "AIM Nosocomial pneumonia ( NP ) and tracheobronchitis after cardiac surgery are associated with worse outcomes . The aim of this study was to identify risk factors associated with NP and tracheobronchitis after cardiac surgery and to determine the impact of these infections on hospital morbidity and mortality . METHODS We evaluated 1600 adult patients undergoing cardiac surgery under st and ard cardiopulmonary bypass . Data were collected prospect ively . All NP and tracheobronchitis episodes were confirmed by a semiquantitative culture of endotracheal aspirate . Logistic regression analysis was done to identify risk factors for respiratory tract infection and mortality . RESULTS The rate of NP was 1.2 % ( 15.6 episodes per 1000 days of mechanical ventilation ) and that of tracheobronchitis was 1.6 % ( 21 episodes per 1000 days of mechanical ventilation ) . Significant independent risk factors for respiratory tract infection ( pneumonia or tracheobronchitis ) were : left ventricular ejection fraction Patients with NP had significantly higher mortality ( 42 % versus 0.9 % , P median hospital length of stay was significantly longer in patients with pneumonia ( 42 days ) and tracheobronchitis ( 28 days ) than in patients without any respiratory tract infection ( 11 days , P < 0.0001 ) . CONCLUSION NP after cardiac surgery is associated with severe outcomes . Independent risk markers for respiratory tract infection were left ventricular ejection fraction < 30 % , chronic renal failure and urgent surgery", "BACKGROUND R and omized , controlled trials have shown that prophylactic antibiotics are effective in preventing surgical-wound infections . However , it is uncertain how the timing of antibiotic administration affects the risk of surgical-wound infection in actual clinical practice . METHODS We prospect ively monitored the timing of antibiotic prophylaxis and studied the occurrence of surgical-wound infections in 2847 patients undergoing elective clean or \" clean-contaminated \" surgical procedures at a large community hospital . The administration of antibiotics 2 to 24 hours before the surgical incision was defined as early ; that during the 2 hours before the incision , as preoperative ; that during the 3 hours after the incision , as perioperative ; and that more than 3 but less than 24 hours after the incision , as postoperative . RESULTS Of the 1708 patients who received the prophylactic antibiotics preoperatively , 10 ( 0.6 percent ) subsequently had surgical-wound infections . Of the 282 patients who received the antibiotics perioperatively , 4 ( 1.4 percent ) had such infections ( P = 0.12 ; relative risk as compared with the preoperatively treated group , 2.4 ; 95 percent confidence interval , 0.9 to 7.9 ) . Of 488 patients who received the antibiotics postoperatively , 16 ( 3.3 percent ) had wound infections ( P less than 0.0001 ; relative risk , 5.8 ; 95 percent confidence interval , 2.6 to 12.3 ) . Finally , of 369 patients who had antibiotics administered early , 14 ( 3.8 percent ) had wound infections ( P less than 0.0001 ; relative risk , 6.7 ; 95 percent confidence interval , 2.9 to 14.7 ) . Stepwise logistic-regression analysis confirmed that the administration of antibiotics in the preoperative period was associated with the lowest risk of surgical-wound infection . CONCLUSIONS We conclude that in surgical practice there is considerable variation in the timing of prophylactic administration of antibiotics and that administration in the two hours before surgery reduces the risk of wound infection", "This clinical trial , which was composed of 1,031 adults undergoing cardiac operations , compared the efficacy of a single dose of 1 g of ceftriaxone with a 48-our regimen consisting of flucloxacillin and gentamicin . There was no significant difference ( p = 0.89 ) in the overall incidence of major infections : 30 of 515 patients ( 5.8 % ; 95 % confidence interval , 5.4 % to 6.2 % ) taking ceftriaxone and 29 of 516 patients ( 5.6 % ; 95 % confidence interval , 5.2 % to 6.0 % ) taking flucloxacillin and gentamicin . Subgroup analyses , with a lower statistical power , failed to show a significant difference between patients who received ceftriaxone and those who received flucloxacillin/gentamicin : major sternal wound infections arose in 2.7 % of the patients taking ceftriaxone versus 1.6 % in those on the 48-hour regimen ( p = 0.20 ) and major limb wound infections arose in 4.2 % and 5.4 % , respectively ( p = 0.44 ) . Single-dose prophylaxis was associated with fewer intravenous administrations ( 864 doses versus 9,570 doses ) and cost less ( A$ 17,248 versus A$ 78,510 ) . Although the regimen that included gentamicin was associated with the greatest biochemical impairment of renal function , the overall toxicity for both groups was low . We conclude that a single dose of ceftriaxone provided cost-efficient prophylaxis for adults undergoing cardiac operations when compared with a 48-hour regimen of gentamicin and flucloxacillin . The general principle revealed by our data is that the short-term administration of an appropriate antibiotic regimen represents optimal prophylaxis for patients undergoing cardiac procedures", "OBJECTIVE In a prospect i ve , r and omized study , postoperatively prolonged antibiotic prophylaxis is evaluated in a high-risk group of patients undergoing cardiac operations . These patients had postoperative low cardiac output necessitating inotropic support and intraaortic balloon pumping . METHODS Between January 1991 and 1994 , 53 patients were enrolled in the study ( 42 men , mean age 65 years ) . All patients received the usual perioperative ( 24 hours ) cefazolin prophylaxis . In the study group ( n = 28 ) a prolonged regimen of prophylaxis with ticarcillin/clavulanate was performed for 2 days and vancomycin was added in a low dose until removal of the intraaortic balloon pump . The control group ( n = 25 ) did not receive a prolonged regimen of prophylaxis . Follow-up ended at hospital discharge . RESULTS Early mortality was 7 of 28 patients ( 25 % ) in the prophylaxis group and 8 of 25 patients ( 32 % ) in the control group ( p = 0.397 ) . Defined infections ( pneumonia , n = 22 ; sepsis , n = 8 ; deep sternal wound infection , n = 2 ) occurred in 50 % of the study group and 68 % of the control group ( p = 0.265 ) . In all patients with septicemia , only coagulase-negative staphylococci could be isolated from the bloodstream ( 5 patients in the prophylaxis group vs 3 in the control group ) . Infectious parameters were controlled daily and did not differ significantly between groups . A total of 1158 bacteriologic tests were performed ( blood cultures , n = 389 ; intravascular catheters , n = 208 ; bronchial aspirates , n = 411 ; intraaortic balloon pumps , n = 42 ; wound secretions , n = 108 ) showing bacterial growth in 322 ( 28 % ) without a significant difference between the groups . In the prophylaxis group , 13 intravascular catheters and intraaortic balloon pumps showed bacterial growth versus 11 in the control group . No side effects were seen . CONCLUSIONS In a high-risk group of patients undergoing cardiac operations , infectious outcome could not be effectively influenced by an additional and prolonged postoperative prophylaxis regimen with low-dose vancomycin and ticarcillin/clavulanate . Low-dose vancomycin did not reduce the rate of infections or colonizations of intravascular catheters with gram-positive organisms", " We r and omized 400 patients who were scheduled for an elective cardiovascular operation involving median sternotomy to receive cefam and ole nafate or cefonicid in a prospect i ve double-blind study . Three hundred fifty-seven patients were evaluable for prophylactic efficacy . Chest wound and donor site infections and early prosthetic valve endocarditis occurred more frequently with cefonicid ( 11 patients , 6.3 % ) than with cefam and ole ( 4 patients , 2.2 % ) ( p = 0.05 ) . Three patients , all in the cefonicid group , required sternal debridement to control postoperative deep wound infections . Twenty-five miscellaneous postoperative infections ( urinary tract infection , pneumonia , intravenous site infection , bacteremia , sepsis , Clostridium difficile diarrhea ) occurred in 16 patients ( 9.19 % ) in the cefonicid group and four in 4 patients ( 2.19 % ) in the cefam and ole group ( p = 0.003 ) . These data indicate that cefam and ole is superior to cefonicid in preventing both surgical wound infections and miscellaneous nonsurgical infections after cardiovascular operations" ]	41188a92-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Hypertension is an important risk factor for adverse cardiovascular events including stroke , myocardial infa rct ion , heart failure and renal failure . The main goal of treatment is to reduce these events . Systematic review s have shown proven benefit of antihypertensive drug therapy in reducing cardiovascular morbidity and mortality but most of the evidence is in people 60 years of age and older . We wanted to know what the effects of therapy are in people 18 to 59 years of age . OBJECTIVES To quantify antihypertensive drug effects on all-cause mortality in adults aged 18 to 59 years with mild to moderate primary hypertension . To quantify effects on cardiovascular mortality plus morbidity ( including cerebrovascular and coronary heart disease mortality plus morbidity ) , withdrawal due adverse events and estimate magnitude of systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) lowering at one year . SEARCH METHODS The Cochrane Hypertension Information Specialist search ed the following data bases for r and omized controlled trials up to January 2017 : the Cochrane Hypertension Specialised Register , the Cochrane Central Register of Controlled Trials ( CENTRAL ) , MEDLINE ( from 1946 ) , Embase ( from 1974 ) , the World Health Organization International Clinical Trials Registry Platform , and Clinical Trials.gov . We contacted authors of relevant papers regarding further published and unpublished work . SELECTION CRITERIA R and omized trials of at least one year ' duration comparing antihypertensive pharmacotherapy with a placebo or no treatment in adults aged 18 to 59 years with mild to moderate primary hypertension defined as SBP 140 mmHg or greater or DBP 90 mmHg or greater at baseline , or both . DATA COLLECTION AND ANALYSIS The outcomes assessed were all-cause mortality , total cardiovascular ( CVS ) mortality plus morbidity , withdrawals due to adverse events , and decrease in SBP and DBP . For dichotomous outcomes , we used risk ratio ( RR ) with 95 % confidence interval ( CI ) and a fixed-effect model to combine outcomes across trials . For continuous outcomes , we used mean difference ( MD ) with 95 % CI and a r and om-effects model as there was significant heterogeneity . MAIN RESULTS The population in the seven included studies ( 17,327 participants ) were predominantly healthy adults with mild to moderate primary hypertension . The Medical Research Council Trial of Mild Hypertension contributed 14,541 ( 84 % ) of total r and omized participants , with mean age of 50 years and mean baseline blood pressure of 160/98 mmHg and a mean duration of follow-up of five years . Treatments used in this study were bendrofluazide 10 mg daily or propranolol 80 mg to 240 mg daily with addition of methyldopa if required . The risk of bias in the studies was high or unclear for a number of domains and led us to down grade the quality of evidence for all outcomes .Based on five studies , antihypertensive drug therapy as compared to placebo or untreated control may have little or no effect on all-cause mortality ( 2.4 % with control vs 2.3 % with treatment ; low quality evidence ; RR 0.94 , 95 % CI 0.77 to 1.13 ) . Based on 4 studies , the effects on coronary heart disease were uncertain due to low quality evidence ( RR 0.99 , 95 % CI 0.82 to 1.19 ) . Low quality evidence from six studies showed that drug therapy may reduce total cardiovascular mortality and morbidity from 4.1 % to 3.2 % over five years ( RR 0.78 , 95 % CI 0.67 to 0.91 ) due to reduction in cerebrovascular mortality and morbidity ( 1.3 % with control vs 0.6 % with treatment ; RR 0.46 , 95 % CI 0.34 to 0.64 ) . Very low quality evidence from three studies showed that withdrawals due to adverse events were higher with drug therapy from 0.7 % to 3.0 % ( RR 4.82 , 95 % CI 1.67 to 13.92 ) . The effects on blood pressure varied between the studies and we are uncertain as to how much of a difference treatment makes on average . AUTHORS ' CONCLUSIONS Antihypertensive drugs used to treat predominantly healthy adults aged 18 to 59 years with mild to moderate primary hypertension have a small absolute effect to reduce cardiovascular mortality and morbidity primarily due to reduction in cerebrovascular mortality and morbidity . All-cause mortality and coronary heart disease were not reduced . There is lack of good evidence on withdrawal due to adverse events . Future trials in this age group should be at least 10 years in duration and should compare different first-line drug classes and strategies	[ "The mechanism of risk reduction obtained by blood pressure-lowering pharmacological treatment remains unclear . We explored the amount of risk reduction attributable to the apparent effect of antihypertensive medicines on blood pressure by using the capture approach . Five r and omized , placebo or nil controlled trials with a total of 28,997 subjects and 1,935 cardiovascular fatal or non-fatal events from the INDANA data base met the eligibility criteria . Computations were performed on the original individual records using multiple Cox 's proportional hazard regression models design ed for meeting the assumed treatment mode of action and comparing relevant assumptions . For coronary event , the results are inconclusive essentially because the risk reduction is mild . However , for stroke the risk reduction adjusted for baseline risk factors is 34 % ( P systolic blood pressure is 49 % of this reduction , with 95 % confidence interval not including 100 % . This result suggests that the apparent effect on blood pressure is not the only cause of stroke risk reduction in hypertensive subjects su bmi tted to an antihypertensive medicine", "Although the benefits of antihypertensive treatment in \" young \" elderly ( under 70 years ) hypertensive patients are well established , the value of treatment in older patients ( 70 - 84 years ) is less clear . The Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension ) was a prospect i ve , r and omised , double-blind , intervention study set up to compare the effects of active antihypertensive therapy ( three beta-blockers and one diuretic ) and placebo on the frequency of fatal and non-fatal stroke and myocardial infa rct ion and other cardiovascular death in hypertensive Swedish men and women aged 70 - 84 years . We recruited 1627 patients at 116 health centres throughout Sweden , who were willing to participate , and who met the entry criteria of three separate recordings during a 1-month placebo run-in period of systolic blood pressure between 180 and 230 mm Hg with a diastolic pressure of at least 90 mm Hg , or a diastolic pressure between 105 and 120 mm Hg irrespective of the systolic pressure . The total duration of the study was 65 months and the average time in the study was 25 months . 812 patients were r and omly allocated active treatment and 815 placebo . The mean difference in supine blood pressure between the active treatment and placebo groups at the last follow-up before an endpoint , death , or study termination was 19.5/8.1 mm Hg . Compared with placebo , active treatment significantly reduced the number of primary endpoints ( 94 vs 58 ; p = 0.0031 ) and stroke morbidity and mortality ( 53 vs 29 ; p = 0.0081 ) . Although we did not set out to study an effect on total mortality , we also noted a significantly reduced number of deaths in the active treatment group ( 63 vs 36 ; p = 0.0079 ) . The benefits of treatment were discernible up to age 84 years . We conclude that antihypertensive treatment in hypertensive men and women aged 70 - 84 confers highly significant and clinical ly relevant reductions in cardiovascular morbidity and mortality as well as in total mortality", "BACKGROUND Questions regarding the efficacy of nonpharmacologic approaches for the treatment of stage 1 hypertension were addressed as part of the Treatment of Mild Hypertension Study ( TOMHS ) , a 4-year , r and omized clinical trial ( N = 902 ) . This report describes the lifestyle intervention program used in TOMHS , presents data on the lifestyle changes observed , and focuses on the effect of weight loss on blood pressure and blood lipid levels . METHODS Participants were r and omly assigned to receive either placebo or one of five different antihypertensive medications . All took part in a lifestyle intervention program to reduce weight and sodium and alcohol intake and to increase physical activity . RESULTS Substantial changes from baseline levels were achieved for all lifestyle intervention variables . Mean weight change was -10.5 lb ( -5.6 % ) at 1 year , -8.5 lb ( -4.5 % ) at 2 years , -7.4 lb ( -4.0 % ) at 3 years , and -5.7 lb ( -3.0 % ) at 4 years . At 4 years , 70 % of participants remained below baseline weight and 34 % maintained a weight loss of 10 lb or greater . Mean change in urinary sodium excretion was -12.5 mmol/8 hr ( -23 % ) at 1 year , -10.7 mmol/8 hr ( -20 % ) at 2 years , -8.4 mmol/8 hr ( -16 % ) at 3 years , and -4.6 mmol/8 hr ( -9 % ) at 4 years . Alcohol intake declined by 1.6 drinks/week among drinkers at 4 years . Reported leisure physical activity increased by 86 % at 1 year and remained 50 % above baseline at 4 years . Beneficial changes in blood pressure and serum lipids were associated with these changes . CONCLUSIONS These results support a role for lifestyle interventions as the initial treatment for stage 1 hypertension and demonstrate that such interventions can be successfully implemented in the clinical setting", "Background — Diuretics are recommended as first-line agents for the treatment of hypertension . This r and omized , double-blind , multicenter study assessed the long-term efficacy and safety of the direct renin inhibitor aliskiren in comparison with the diuretic hydrochlorothiazide in patients with essential hypertension . Methods and Results — After a 2- to 4-week placebo run-in , 1124 patients ( mean sitting diastolic blood pressure [ BP ] 95 to 109 mm Hg ) were r and omized to aliskiren 150 mg ( n=459 ) , hydrochlorothiazide 12.5 mg ( n=444 ) , or placebo ( n=221 ) once daily . Forced titration ( to aliskiren 300 mg or hydrochlorothiazide 25 mg ) occurred at week 3 ; at week 6 , patients receiving placebo were reassigned ( 1:1 ratio ) to aliskiren 300 mg or hydrochlorothiazide 25 mg . From week 12 , amlodipine 5 mg was added and titrated to 10 mg from week 18 for patients whose BP remained uncontrolled . Efficacy variables were analyzed for the intent-to-treat population with the use of the last observation carried forward method . BP reductions ( mean sitting systolic BP/mean sitting diastolic BP ) were significantly greater with aliskiren- versus hydrochlorothiazide-based treatment at week 26 ( −20.3/−14.2 versus −18.6/−13.0 mm Hg ; P for mean sitting diastolic BP ) . At the end of the monotherapy period ( week 12 ) , aliskiren 300 mg was superior to hydrochlorothiazide 25 mg in reducing BP ( −17.4/−12.2 versus −14.7/−10.3 mm H ; P rates were similar with aliskiren- ( 65.2 % ) and hydrochlorothiazide-based therapy ( 61.5 % ) . Hypokalemia was more frequent with hydrochlorothiazide-based therapy than aliskiren-based therapy ( 17.9 % versus 0.9 % ; P Aliskiren treatment , both as monotherapy and with optional addition of amlodipine , provided significantly greater BP reductions than the respective hydrochlorothiazide regimens . Aliskiren-based therapy was well tolerated . Direct renin inhibition with aliskiren therefore represents an effective option for the long-term treatment of essential hypertension", "Background The risks and benefits of treating hypertension in individuals older than 80 years are uncertain . A meta- analysis has suggested that a reduction in stroke events of 36 % may have to be balanced against a 14 % increase in total mortality . Objectives To report the results of the pilot study of the Hypertension in the Very Elderly Trial ( HYVET ) , which is in progress to address these issues . Methods The HYVET-Pilot was a multicentre international open pilot trial . In 10 European countries , 1283 patients older than 80 years and with a sustained blood pressure of 160–219/90–109 mmHg were allocated r and omly to one of three treatments : a diuretic-based regimen ( usually bendroflumethiazide ; n = 426 ) , an angiotensin-converting enzyme inhibitor regimen ( usually lisinopril ; n = 431 ) or no treatment ( n = 426 ) . The procedure permitted doses of the drug to be titrated and diltiazem slow-release to be added to active treatment . Target blood pressure was the reduction in stroke events relative hazard rate ( RHR ) was 0.47 [ 95 % confidence interval ( CI ) 0.24 to 0.93 ] and the reduction in stroke mortality RHR was 0.57 ( 95 % CI 0.25 to 1.32 ) . However , the estimate of total mortality supported the possibility of excess deaths with active treatment ( RHR 1.23 , 95 % CI 0.75 to 2.01 ) . Conclusions The preliminary results support the need for the continuing main HYVET trial . It is possible that treatment of 1000 patients for 1 year may reduce stroke events by 19 ( nine non-fatal ) , but may be associated with 20 extra non-stroke deaths ", "Patients with mild to moderate essential hypertension were treated mainly with an ACE inhibitor ( delapril , n = 980 ) or a Ca antagonist ( n = 956 ) for 12 months , and the incidence of cerebrovascular and cardiovascular events as well as drug-related side effects were compared between the two groups . There were no significant differences between the clinical background s of the two groups . In both groups , the blood pressure was decreased significantly from 1 month of treatment onwards , with the degree of reduction being greater in the Ca antagonist group throughout the study period ( p Cerebrovascular or cardiovascular events occurred in 11 out of 980 patients in the delapril group and 18 out of 956 patients in the Ca antagonist group ( p = NS ) . Cerebrovascular disease developed in 5 delapril-treated patients and 11 Ca antagonist-treated patients , and heart disease developed in 5 and 7 patients , respectively ( both p = NS ) . Discontinuation of treatment due to side effects was significantly more common in the delapril group than in the Ca antagonist group ( p incidence of cerebrovascular and cardiovascular events between the two groups , and the results suggested that blood pressure reduction per se did not necessarily lead to a parallel decrease in cerebrovascular and cardiovascular complications", "BACKGROUND Calcium antagonists are a first-line treatment for hypertension . The effectiveness of diltiazem , a non-dihydropyridine calcium antagonist , in reducing cardiovascular morbidity or mortality is unclear . We compared the effects of diltiazem with that of diuretics , beta-blockers , or both on cardiovascular morbidity and mortality in hypertensive patients . METHODS In a prospect i ve , r and omised , open , blinded endpoint study , we enrolled 10,881 patients , aged 50 - 74 years , at health centres in Norway and Sweden , who had diastolic blood pressure of 100 mm Hg or more . We r and omly assigned patients diltiazem , or diuretics , beta-blockers , or both . The combined primary endpoint was fatal and non-fatal stroke , myocardial infa rct ion , and other cardiovascular death . Analysis was done by intention to treat . FINDINGS Systolic and diastolic blood pressure were lowered effectively in the diltiazem and diuretic and beta-blocker groups ( reduction 20.3/18.7 vs 23.3/18.7 mm Hg ; difference in systolic reduction p Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 in the diuretic and beta-blocker group ( 6.4 vs 7.9 events per 1000 patient-years ; 0.80 [ 0.65 - 0.99 ] , p=0.04 ) and fatal and non-fatal myocardial infa rct ion in 183 and 157 patients ( 7.4 vs 6.3 events per 1000 patient-years ; 1.16 [ 0.94 - 1.44 ] , p=0.17 ) . INTERPRETATION Diltiazem was as effective as treatment based on diuretics , beta-blockers , or both in preventing the combined primary endpoint of all stroke , myocardial infa rct ion , and other cardiovascular death", "BACKGROUND It is unknown whether either the angiotensin-II-receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure . METHODS We r and omly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan ( 300 mg daily ) , amlodipine ( 10 mg daily ) , or placebo . The target blood pressure was 135/85 mm Hg or less in all groups . We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line serum creatinine concentration , the development of end-stage renal disease , or death from any cause . We also compared them with regard to the time to a secondary , cardiovascular composite end point . RESULTS The mean duration of follow-up was 2.6 years . Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo group ( P=0.02 ) and 23 percent lower than that in the amlodipine group ( P=0.006 ) . The risk of a doubling of the serum creatinine concentration was 33 percent lower in the irbesartan group than in the placebo group ( P=0.003 ) and 37 percent lower in the irbesartan group than in the amlodipine group ( P irbesartan was associated with a relative risk of end-stage renal disease that was 23 percent lower than that in both other groups ( P=0.07 for both comparisons ) . These differences were not explained by differences in the blood pressures that were achieved . The serum creatinine concentration increased 24 percent more slowly in the irbesartan group than in the placebo group ( P=0.008 ) and 21 percent more slowly than in the amlodipine group ( P=0.02 ) . There were no significant differences in the rates of death from any cause or in the cardiovascular composite end point . CONCLUSIONS The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes . This protection is independent of the reduction in blood pressure it causes", "Summary The Syst-Eur Trial is a concerted action of the European Community ’s Medical and Health Research Programme . The trial is carried out in consultation with the World Health Organization , the International Society of Hypertension , the European Society of Hypertension and the World Hypertension League . This article describes the objectives and the protocol of Syst-Eur , a multicentre trial design ed by the European Working Party on High Blood . Pressure in the Elderly ( EWPHE ) , to test the hypothesis that antihypertensive treatment of elderly patients with isolated systolic hypertension results in a significant change in stroke morbidity and mortality . Secondary endpoints include cardiovascular events , such as myocardial infa rct ion and congestive heart failure . To be eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160–219 mmHg with a diastolic pressure less than 95 mmHg . Patients must give their informed consent and be free of major cardiovascular and non-cardiovascular diseases at entry . The patients are r and omized to active treatment or placebo . Active treatment consists of nitrendipine ( 10–40 mg/day ) , combined with enalapril ( 5–20 mg/day ) and hydrochlorothiazide ( 12.5–25 mg/day ) , as necessary . The patients of the control group receive matching placebos . The drugs ( or matching placebos ) are stepwise titrated and combined in order to reduce systolic blood pressure by 20 mmHg at least to a level below 150 mmHg . Morbidity and mortality are monitored to enable an intention-to-treat and per protocol comparison of the outcome in the 2 treatment groups . A one-year pilot trial ( 1989 ) showed that the protocol is practicable . The Ethics Committee therefore decided to start the definite study ( 1990 ) , in which r and omized patients will be followed for 5 years . Recruitment of new centres and of the required 3,000 patients will last 3 years ( until 1993 )", "Abstract A prospect i ve r and omised controlled trial of hypotensive therapy in 97 hypertensive patients surviving an ischaemic-type stroke was started in 1964 and terminated 4 years later . The patients were under 80 years of age , consecutively admitted to one hospital and the control and treated groups compared well for age , sex , and severity of hypertension . The drugs used were methyldopa , bethanidine or debrisoquine combined with restriction of salt intake , weight reduction , and thiazide diuretics , and the results were analysed with regard to survival and recurrence rates . Hypertension was defined as diastolic if this pressure was 110 mm . Hg or above , and as systolic if this pressure was over 160 mm . Hg with the diastolic below 110 mm . Hg . The mortality-rate at the end of a 2 to 5 year followup was 26 % in the treated group and 46 % in the untreated , and the non-fatal recurrence-rate 14 % in the treated and 23 % in the controls . Good smooth control was essential to success , untreated patients doing better than those whose control was unsatisfactory . In patients aged over 65 treatment of systolic hypertension was of no benefit , although the diastolic hypertensives improved marginally with treatment . As age increased this effect was progressively less apparent but the figures are probably too small to mean anything . In this series significant improvement occurred in treated hypertensive patients who had survived a stroke if they were aged 65 or below , but not if they were older", " A total of 123 out of 549 elderly residents of local authority welfare homes in Nottinghamshire were found at screening to have a st and ing or lying diastolic blood pressure of 100 mm Hg or more . These 123 subjects were r and omly allocated to simple observation or to treatment with methyldopa . The cumulative mortality was similar in the observed and treated groups and in the normotensive group from which the subjects had been separated . Thus moderate hypertension , whether treated or not , was not a major risk predictor in the elderly population studied", "The Hypertension Detection and Follow-up Program screened 34,012 individuals aged 60 - 69 years old in their homes in 14 communities around the United States during 1972 and 1973 . The prevalence of hypertension , defined as diastolic blood pressure greater than or equal to 90 mmHg or on antihypertensive medication , was 42.1 % . After a second clinic screen , 2,376 hypertensives were identified and r and omized into Stepped Care , a special intensive treatment group , or Referred Care , a group referred to their usual medical care sources . These individuals were followed for five years ( until they reached the ages of 65 - 74 years ) . Over the five years , 79.4 % of older individuals remained under active care and 81.4 % of those were at their goal diastolic blood pressure . Side-effects tended to be less frequent in older individuals than in younger ones . Older Stepped Care participants with mild hypertension ( diastolic blood pressure 90 - 104 mmHg ) had a 17.2 % reduction in all-cause mortality over five years compared to Referred Care , which was primarily due to a reduction in deaths attributed to cardiovascular causes . Thus , antihypertensive treatment can be safely and beneficially administered to individuals in this age range with diastolic hypertension , including those with mild hypertension", "Background Blood pressure ( BP ) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension , which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age . Non-drug interventions to prevent hypertension have had low effectiveness . In individuals with previous cardiovascular disease or diabetes , the use of BP-lowering agents reduces the incidence of major cardiovascular events . In the absence of higher baseline risk , the use of BP agents reduces the incidence of hypertension . The PREVER-prevention trial aims to investigate the efficacy , safety and feasibility of a population -based intervention to prevent the incidence of hypertension and the development of target-organ damage . Methods This is a r and omized , double-blind , placebo-controlled clinical trial , with participants aged 30 to 70 years , with pre-hypertension . The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo . The primary outcomes will be the incidence of hypertension , adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG . The secondary outcomes will be fatal or non-fatal cardiovascular events : myocardial infa rct ion , stroke , heart failure , evidence of new sub- clinical atherosclerosis , and sudden death . The study will last 18 months . The sample size was calculated on the basis of an incidence of hypertension of 14 % in the control group , a size effect of 40 % , power of 85 % and P alpha of 5 % , result ing in 625 participants per group . The project was approved by the Ethics committee of each participating institution . Discussion The early use of blood pressure-lowering drugs , particularly diuretics , which act on the main mechanism of blood pressure rising with age , may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension . If this intervention shows to be effective and safe in a population -based perspective , it could be the basis for an innovative public health program to prevent hypertension in Brazil . Trial Registration Clinical Trials NCT00970931", "Abstract Objective : To determine whether tight control of blood pressure with either a β blocker or an angiotensin converting enzyme inhibitor has a specific advantage or disadvantage in preventing the macrovascular and microvascular complications of type 2 diabetes . Design : R and omised controlled trial comparing an angiotensin converting enzyme inhibitor ( captopril ) with a β blocker ( atenolol ) in patients with type 2 diabetes aim ing at a blood pressure of Setting : 20 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Subjects : 1148 hypertensive patients with type 2 diabetes ( mean age 56 years , mean blood pressure 160/94 mm Hg ) . Of the 758 patients allocated to tight control of blood pressure , 400 were allocated to captopril and 358 to atenolol . 390 patients were allocated to less tight control of blood pressure . Main outcome measures : Predefined clinical end points , fatal and non-fatal , related to diabetes , death related to diabetes , and all cause mortality . Surrogate measures of microvascular and macrovascular disease included urinary albumin excretion and retinopathy assessed by retinal photography . Results : Captopril and atenolol were equally effective in reducing blood pressure to a mean of 144/83 mm Hg and 143/81 mm Hg respectively , with a similar proportion of patients ( 27 % and 31 % ) requiring three or more antihypertensive treatments . More patients in the captopril group than the atenolol group took the allocated treatment : at their last clinic visit , 78 % of those allocated captopril and 65 % of those allocated atenolol were taking the drug ( P Captopril and atenolol were equally effective in reducing the risk of macrovascular end points . Similar proportions of patients in the two groups showed deterioration in retinopathy by two grade s after nine years ( 31 % in the captopril group and 37 % in the atenolol group ) and developed clinical grade albuminuria ≥300 mg/l ( 5 % and 9 % ) . The proportion of patients with hypoglycaemic attacks was not different between groups , but mean weight gain in the atenolol group was greater ( 3.4 kg v 1.6 kg ) . Conclusion : Blood pressure lowering with captopril or atenolol was similarly effective in reducing the incidence of diabetic complications . This study provided no evidence that either drug has any specific beneficial or deleterious effect , suggesting that blood pressure reduction in itself may be more important than the treatment used", "BACKGROUND Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear . It has been suggested that antihypertensive therapy may reduce the risk of stroke , despite possibly increasing the risk of death . METHODS We r and omly assigned 3845 patients from Europe , China , Australasia , and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide ( sustained release , 1.5 mg ) or matching placebo . The angiotensin-converting-enzyme inhibitor perindopril ( 2 or 4 mg ) , or matching placebo , was added if necessary to achieve the target blood pressure of 150/80 mm Hg . The primary end point was fatal or nonfatal stroke . RESULTS The active-treatment group ( 1933 patients ) and the placebo group ( 1912 patients ) were well matched ( mean age , 83.6 years ; mean blood pressure while sitting , 173.0/90.8 mm Hg ) ; 11.8 % had a history of cardiovascular disease . Median follow-up was 1.8 years . At 2 years , the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group . In an intention-to-treat analysis , active treatment was associated with a 30 % reduction in the rate of fatal or nonfatal stroke ( 95 % confidence interval [ CI ] , -1 to 51 ; P=0.06 ) , a 39 % reduction in the rate of death from stroke ( 95 % CI , 1 to 62 ; P=0.05 ) , a 21 % reduction in the rate of death from any cause ( 95 % CI , 4 to 35 ; P=0.02 ) , a 23 % reduction in the rate of death from cardiovascular causes ( 95 % CI , -1 to 40 ; P=0.06 ) , and a 64 % reduction in the rate of heart failure ( 95 % CI , 42 to 78 ; P serious adverse events were reported in the active-treatment group ( 358 , vs. 448 in the placebo group ; P=0.001 ) . CONCLUSIONS The results provide evidence that antihypertensive treatment with indapamide ( sustained release ) , with or without perindopril , in persons 80 years of age or older is beneficial . ( Clinical Trials.gov number , NCT00122811 [ Clinical Trials.gov ] . )", "The pilot study of the Systolic Hypertension in the Elderly Program was a r and omized , double-blind , placebo-controlled trial of drug therapy for isolated systolic hypertension . It followed 551 elderly participants with untreated blood pressures of greater than 160/less than 90 mm Hg for an average of 34 months . Mean age of the participants was 72 years ; 63 % were women , and 82 % were white . Pretreatment blood pressures averaged 172/75 mm Hg . Participants were r and omly assigned to treatment with chlorthalidone or placebo as Step I medication . Blood pressures at annual visits averaged 141/68 and 157/73 mm Hg for the drug-treated and placebo-treated groups , respectively , with 60 % and 33 % of the survivors on blinded medication having systolic blood pressures of less than 160 mm Hg at their last annual visit . All-cause mortality rates for the drug-treated and placebo-treated groups were 25.4 and 22.7 deaths per 1,000 participant-years of risk , and rates for definite \" first stroke \" were 8.3 and 12.8 per 1,000 years of risk . Differences between groups were significant for systolic and diastolic blood pressure but not for death or stroke rates . A full-scale study has begun to determine the effects of drug therapy for isolated systolic hypertension on stroke and mortality rates", "BACKGROUND Observational epidemiological studies have shown a positive association between hypertension and risk of incident dementia ; however , the effects of antihypertensive therapy on cognitive function in controlled trials have been conflicting , and meta-analyses of the trials have not provided clear evidence of whether antihypertensive treatment reduces dementia incidence . The Hypertension in the Very Elderly trial ( HYVET ) was design ed to assess the risks and benefits of treatment of hypertension in elderly patients and included an assessment of cognitive function . METHODS Patients with hypertension ( systolic pressure 160 - 200 mm Hg ; diastolic pressure in this double-blind , placebo-controlled trial . Participants were r and omly assigned to receive 1.5 mg slow release indapamide , with the option of 2 - 4 mg perindopril , or placebo . The target systolic blood pressure was 150 mm Hg ; the target diastolic blood pressure was 80 mm Hg . Participants had no clinical diagnosis of dementia at baseline , and cognitive function was assessed at baseline and annually with the mini-mental state examination ( MMSE ) . Possible cases of incident dementia ( a fall in the MMSE score to stroke and total mortality . Analysis was by intention to treat . The trial is registered with Clinical Trials.gov , number NCT00122811 . FINDINGS 3336 HYVET participants had at least one follow-up assessment ( mean 2.2 years ) and were included : 1687 participants were r and omly assigned to the treatment group and 1649 to the placebo group . Only five reports of adverse effects were attributed to the medication : three in the placebo group and two in the treatment group . The mean decrease in systolic blood pressure between the treatment and placebo groups at 2 years was systolic -15 mm Hg , p dementia . The rates of incident dementia were 38 per 1000 patient-years in the placebo group and 33 per 1000 patient-years in the treatment group . There was no significant difference between treatment and placebo groups ( hazard ratio [ HR ] 0.86 , 95 % CI 0.67 - 1.09 ) ; however , when these data were combined in a meta- analysis with other placebo-controlled trials of antihypertensive treatment , the combined risk ratio favoured treatment ( HR 0.87 , 0.76 - 1.00 , p=0.045 ) . INTERPRETATION Antihypertensive treatment in elderly patients does not statistically reduce incidence of dementia . This negative finding might have been due to the short follow-up , owing to the early termination of the trial , or the modest effect of treatment . Nevertheless , the HYVET findings , when included in a meta- analysis , might support antihypertensive treatment to reduce incident dementia", "Direct evidence about the effects of antihypertensive treatment on vascular disease in older patients is available from five r and omized trials conducted exclusively in patients over the age of 60 years . These trials involved a total of 12,483 individuals with systolic or diastolic hypertension ( mean age = 72 years , mean entry blood pressure = 181/88 mmHg ) . Over an average follow-up period of 4.7 years , a 15/6 mmHg difference in blood pressure between study and control groups was achieved . Among those patients assigned active treatment , stroke incidence was reduced by 34 % SD6 and coronary heart disease incidence was reduced by 19 % SD7 . These proportional reductions were of similar size to those observed in trials in predominantly younger patients . However , the absolute benefits observed in older patients were more than twice as great as those observed in younger patients . The results suggest that over 10 years , treatment would prevent at least one major vascular event among every 10 elderly patients at similar risk to those enrolled in the trials", "The pilot phase of the British multicentre r and omized controlled trial of treatment for mild hypertension has shown : ( 1 ) that unselected subjects , aged 35 - 64 years , with mild hypertension are willing to enter and remain in a long-term trial even though asymptomatic ; ( 2 ) that the differences of mean systolic and mean diastolic pressure achieved between treated and control subjects is sufficient to produce the expected difference in terminating events with the 18000 patients calculated as needed for the full-scale trial ; ( 3 ) that side effects with the two selected active primary regimens ( bendrofluazide and propranolol ) are common but mild ( no serious side effects or toxic reactions have been reported ) ; ( 4 ) that the work load imposed by the trial , though considerable during screening and the initiation of patients into the trial , can largely be taken by specially trained nursing staff , and when screening is completed the trial does not impose a heavy burden of follow-up examinations ; ( 5 ) that there are no adverse psychological effects caused by alerting asymptomatic people to their raised pressure and enrolling them into a prolonged programme of clinical attendance ; ( 6 ) that the total costs of carrying out a full-scale trial -- estimated at about lb.2 m ( $ U.S. 4m)--are commensurate with the potential annual savings in health service expenditure whether the trial shows treatment to be effective or unwarranted", "As sub studies of the Medical Research Council 's trials of treatment of mild hypertension and of hypertension in the elderly , two studies were carried out comparing the effects of different doses of two diuretics on blood pressure , concentrations of some biochemical variables , and the incidence of subjective adverse reactions . In one study , in which 484 patients with mild hypertension participated , daily doses of bendrofluazide 5 mg and 10 mg , with and without oral potassium supplements , were compared . In the second , involving 701 elderly patients with hypertension , daily doses of hydrochlorothiazide 25 mg together with amiloride 2.5 mg were compared with hydrochlorothiazide 50 mg together with amiloride 5 mg . The mean ( + /- SD ) duration s of treatment were 35 + /- 17 months in the first study and 10 + /- 7 months in the second . Neither study showed any significant difference in blood pressure response to the two doses of diuretic , whereas biochemical changes and the reported incidence of subjective adverse reactions were dose-related . In the first study , potassium supplementation with potassium chloride 16.8 or 33.6 mmol did not have a significant effect on the fall in serum potassium level , which was only slightly reduced , and did not have any significant effect on the antihypertensive effect of either dose of bendrofluazide", "BACKGROUND Blood pressure is an important determinant of the risks of macrovascular and microvascular complications of type 2 diabetes , and guidelines recommend intensive lowering of blood pressure for diabetic patients with hypertension . We assessed the effects of the routine administration of an angiotensin converting enzyme ( ACE ) inhibitor-diuretic combination on serious vascular events in patients with diabetes , irrespective of initial blood pressure levels or the use of other blood pressure lowering drugs . METHODS The trial was done by 215 collaborating centres in 20 countries . After a 6-week active run-in period , 11 140 patients with type 2 diabetes were r and omised to treatment with a fixed combination of perindopril and indapamide or matching placebo , in addition to current therapy . The primary endpoints were composites of major macrovascular and microvascular events , defined as death from cardiovascular disease , non-fatal stroke or non-fatal myocardial infa rct ion , and new or worsening renal or diabetic eye disease , and analysis was by intention-to-treat . The macrovascular and microvascular composites were analysed jointly and separately . This trial is registered with Clinical Trials.gov , number NCT00145925 . FINDINGS After a mean of 4.3 years of follow-up , 73 % of those assigned active treatment and 74 % of those assigned control remained on r and omised treatment . Compared with patients assigned placebo , those assigned active therapy had a mean reduction in systolic blood pressure of 5.6 mm Hg and diastolic blood pressure of 2.2 mm Hg . The relative risk of a major macrovascular or microvascular event was reduced by 9 % ( 861 [ 15.5 % ] active vs 938 [ 16.8 % ] placebo ; hazard ratio 0.91 , 95 % CI 0.83 - 1.00 , p=0.04 ) . The separate reductions in macrovascular and microvascular events were similar but were not independently significant ( macrovascular 0.92 ; 0.81 - 1.04 , p=0.16 ; microvascular 0.91 ; 0.80 - 1.04 , p=0.16 ) . The relative risk of death from cardiovascular disease was reduced by 18 % ( 211 [ 3.8 % ] active vs 257 [ 4.6 % ] placebo ; 0.82 , 0.68 - 0.98 , p=0.03 ) and death from any cause was reduced by 14 % ( 408 [ 7.3 % ] active vs 471 [ 8.5 % ] placebo ; 0.86 , 0.75 - 0.98 , p=0.03 ) . There was no evidence that the effects of the study treatment differed by initial blood pressure level or concomitant use of other treatments at baseline . INTERPRETATION Routine administration of a fixed combination of perindopril and indapamide to patients with type 2 diabetes was well tolerated and reduced the risks of major vascular events , including death . Although the confidence limits were wide , the results suggest that over 5 years , one death due to any cause would be averted among every 79 patients assigned active therapy", "Abstract Objective : To determine whether tight control of blood pressure prevents macrovascular and microvascular complications in patients with type 2 diabetes . Design : R and omised controlled trial comparing tight control of blood pressure aim ing at a blood pressure of angiotensin converting enzyme inhibitor captopril or a β blocker atenolol as main treatment ) with less tight control aim ing at a blood pressure of 20 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Subjects : 1148 hypertensive patients with type 2 diabetes ( mean age 56 , mean blood pressure at entry 160/94 mm Hg ) ; 758 patients were allocated to tight control of blood pressure and 390 patients to less tight control with a median follow up of 8.4 years . Main outcome measures : Predefined clinical end points , fatal and non-fatal , related to diabetes , deaths related to diabetes , and all cause mortality . Surrogate measures of microvascular disease included urinary albumin excretion and retinal photography . Results : Mean blood pressure during follow up was significantly reduced in the group assigned tight blood pressure control ( 144/82 mm Hg ) compared with the group assigned to less tight control ( 154/87 mm Hg ) ( P Reductions in risk in the group assigned to tight control compared with that assigned to less tight control were 24 % in diabetes related end points ( 95 % confidence interval 8 % to 38 % ) ( P=0.0046 ) , 32 % in deaths related to diabetes ( 6 % to 51 % ) ( P=0.019 ) , 44 % in strokes ( 11 % to 65 % ) ( P=0.013 ) , and 37 % in microvascular end points ( 11 % to 56 % ) ( P=0.0092 ) , predominantly owing to a reduced risk of retinal photocoagulation . There was a non-significant reduction in all cause mortality . After nine years of follow up the group assigned to tight blood pressure control also had a 34 % reduction in risk in the proportion of patients with deterioration of retinopathy by two steps ( 99 % confidence interval 11 % to 50 % ) ( P=0.0004 ) and a 47 % reduced risk ( 7 % to 70 % ) ( P=0.004 ) of deterioration in visual acuity by three lines of the early treatment of diabetic retinopathy study ( ETDRS ) chart . After nine years of follow up 29 % of patients in the group assigned to tight control required three or more treatments to lower blood pressure to achieve target blood pressures . Conclusion : Tight blood pressure control in patients with hypertension and type 2 diabetes achieves a clinical ly important reduction in the risk of deaths related to diabetes , complications related to diabetes , progression of diabetic retinopathy , and deterioration in visual acuity", "It is well established that hypertensive patients benefit from drug treatment of their disorder . In recent years three major out-come studies of antihypertensive treatment in elderly hypertensives have shown substantial benefits , i.e. a reduction in the risk of stroke and other cardiovascular mortality and morbidity . In all these studies beta-blockers and /or diuretics were used in comparison with placebo . Newer therapeutic alternatives have , however , at least theoretically , many advantages which could result in further improvements in prognosis . The initial Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension 1 ) was conducted in men and women aged 70 - 84 years . STOP-Hypertension 2 will evaluate the therapy used in STOP-Hypertension 1 against therapy based on either ACE-inhibitors ( enalapril and lisinopril ) or on calcium antagonists ( isradipine and felodipine ) , using the PROBE design ( Prospect i ve , R and omised , Open , Blinded Endpoint evaluation ) . The primary aim will be to assess the effect on cardiovascular mortality . Statistical calculations indicate that 6,600 patients , followed for four years will be needed ( 2p or = 180/105 mmHg ( and /or ) . Recruitment of patients started in September 1992 and so far more than 100 patients /week have been included", "The never-treated control group in the Oslo Study hypertension trial of middle-aged men 40 - 49 years old at entry ( n = 379 ) was studied with respect to five-year change in blood pressure and its correlates . The study began in 1972 and ended in 1979 , and each patient was followed for five years . Both baseline and rate of change of correlates were analyzed as independent variables versus rate of change in blood pressure as the dependent variable . Rate of change in serum triglycerides were found to be the strongest correlate of rate of change in blood pressure in this population of healthy mild hypertensives . In addition , rate of change in serum cholesterol and body weight made significant contributions in some analyses , but to a lower degree than did rate of change in triglycerides . The model predicts a substantial decrease in blood pressure if lipids and body weight are reduced . Rate of change in sodium , uric acid , and chloride concentrations were also associated with blood pressure change , but total degree of explanation of all explaining variables only accounted for 11 - 15 % of total variation in annual blood pressure change", "Background The prognostic benefits of blood pressure lowering treatment in elderly hypertensive patients were established more than a decade ago , but are less clear in those with mildly to moderately elevated blood pressure . Objective To assess whether c and esartan-based antihypertensive treatment in elderly patients with mildly to moderately elevated blood pressure confers a reduction in cardiovascular events , cognitive decline and dementia . Design Prospect i ve , double-blind , r and omized , parallel-group study conducted in 1997–2002 . Setting and participants The study was of 4964 patients aged 70–89 years , with systolic blood pressure 160–179 mmHg , and /or diastolic blood pressure 90–99 mmHg , and a Mini Mental State Examination ( MMSE ) test score ⩾ 24 . A total of 527 centres in 15 countries participated in the study . Intervention Patients were assigned r and omly to receive the angiotensin receptor blocker c and esartan or placebo , with open-label active antihypertensive therapy added as needed . As a consequence , active antihypertensive therapy was extensively used in the control group ( 84 % of patients ) . Mean follow-up was 3.7 years . Main outcome measures The primary outcome measure was major cardiovascular events , a composite of cardiovascular death , non-fatal stroke and non-fatal myocardial infa rct ion . Secondary outcome measures included cardiovascular death , non-fatal and fatal stroke and myocardial infa rct ion , cognitive function measured by the MMSE and dementia . Results Blood pressure fell by 21.7/10.8 mmHg in the c and esartan group and by 18.5/9.2 mmHg in the control group . A first major cardiovascular event occurred in 242 c and esartan patients and in 268 control patients ; risk reduction with c and esartan was 10.9 % [ 95 % confidence interval ( CI ) , −6.0 to 25.1 , P = 0.19 ] . C and esartan-based treatment reduced non-fatal stroke by 27.8 % ( 95 % CI , 1.3 to 47.2 , P = 0.04 ) , and all stroke by 23.6 % ( 95 % CI , −0.7 to 42.1 , P = 0.056 ) . There were no significant differences in myocardial infa rct ion and cardiovascular mortality . Mean MMSE score fell from 28.5 to 28.0 in the c and esartan group and from 28.5 to 27.9 in the control group ( P = 0.20 ) . The proportions of patients who had a significant cognitive decline or developed dementia were not different in the two treatment groups . Conclusions In elderly hypertensive patients , a slightly more effective blood pressure reduction during c and esartan-based therapy , compared with control therapy , was associated with a modest , statistically non-significant , reduction in major cardiovascular events and with a marked reduction in non-fatal stroke . Cognitive function was well maintained in both treatment groups in the presence of substantial blood pressure reductions . Both treatment regimens were generally well tolerated", "Summary The Oslo Hypertension Study started in 1972 and lasted for 66 ( range 60–78 ) months . A total of 785 healthy men , aged 40 to 49 years , with mild hypertension were r and omised to a drug-treated group and to an untreated , control group . The drugs used for treatment were hydrochlorothiazide alone in 36 % , hydrochlorothiazide and propranolol in 26 % , hydrochlorothiazide and methyldopa in 20 % , and other drugs in 18%.A total of 95 % in the drug-treated group received hydrochlorothiazide . Pressure complications , such as stroke and aneurysms , only occurred in the control group . Coronary events were more numerous in the drug-treated group , so that the total incidence of cardiovascular complications did not significantly differ between the treated and untreated groups . After 5 and 10 years , total mortality was found to be the same in both groups . However , the 10-year coronary heart disease mortality was significantly higher in the drug-treated group than in the untreated controls ( 14 vs 3 , p of hypertension on coronary heart disease is discussed , and attention is drawn to the adverse effect of diuretics and β-adrenergic blockers , both on lipid and carbohydrate metabolism . This is in contrast to the α-adrenergic blocker , prazosin , which has been shown to improve the blood lipid profile ", "The European Working Party on High Blood Pressure in the Elderly study ( EWPHE ) was a placebo-controlled , double-blind , inter-patient assessment of diuretic treatment in hypertensive patients aged 60 years or more . Of the 840 patients included in the study 247 had isolated systolic hypertension ( systolic blood pressure greater than or equal to 160 and diastolic blood pressure less than or equal to 95 mmHg ) . In those ( n = 120 ) r and omized to active treatment ( diazide-hydrochlorothiazide with triamterene + /- methyldopa ) blood pressure after 3 years was , on average , 19/8 mmHg lower than in the placebo group ( n = 119 ) and after 5 years the difference was 9/7 mmHg . Data on mortality and morbidity were insufficient for firm conclusions to be drawn . The data are presented here only to communicate the trends observed and to provide information that may be useful in the design of future trials . The trends observed for cardiac mortality , terminating non-fatal events ( including severe heart failure ) and combined fatal and non-fatal cardiovascular events follow a similar pattern to that observed in the trial overall , in that active treatment appeared to confer benefit . However , in the case of isolated systolic hypertension none of these differences between active and placebo treatment achieved statistical significance . We conclude that , given the epidemiological data incriminating systolic hypertension as a risk factor and the data presented here , a rigorous assessment of the value of treating isolated systolic hypertension is justified", "BACKGROUND Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction , whether or not they have heart failure . We assessed the role of an angiotensin-converting-enzyme inhibitor , ramipril , in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure . METHODS A total of 9297 high-risk patients ( 55 years of age or older ) who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were r and omly assigned to receive ramipril ( 10 mg once per day orally ) or matching placebo for a mean of five years . The primary outcome was a composite of myocardial infa rct ion , stroke , or death from cardiovascular causes . The trial was a two-by-two factorial study evaluating both ramipril and vitamin E. The effects of vitamin E are reported in a companion paper . RESULTS A total of 651 patients who were assigned to receive ramipril ( 14.0 percent ) reached the primary end point , as compared with 826 patients who were assigned to receive placebo ( 17.8 percent ) ( relative risk , 0.78 ; 95 percent confidence interval , 0.70 to 0.86 ; P rates of death from cardiovascular causes ( 6.1 percent , as compared with 8.1 percent in the placebo group ; relative risk , 0.74 ; P myocardial infa rct ion ( 9.9 percent vs. 12.3 percent ; relative risk , 0.80 ; P stroke ( 3.4 percent vs. 4.9 percent ; relative risk , 0.68 ; P death from any cause ( 10.4 percent vs. 12.2 percent ; relative risk , 0.84 ; P=0.005 ) , revascularization procedures ( 16.3 percent vs. 18.8 percent ; relative risk , 0.85 ; P cardiac arrest ( 0.8 percent vs. 1.3 percent ; relative risk , 0.62 ; P=0.02 ) , [ corrected ] heart failure ( 9.1 percent vs. 11.6 percent ; relative risk , 0.77 ; P complications related to diabetes ( 6.4 percent vs. 7.6 percent ; relative risk , 0.84 ; P=0.03 ) . CONCLUSIONS Ramipril significantly reduces the rates of death , myocardial infa rct ion , and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure", "OBJECTIVE To investigate the long-term effects of multifactorial primary prevention of cardiovascular diseases ( CVD ) . DESIGN The 5-year r and omized , controlled trial was performed between 1974 and 1980 . The subjects and their risk factors were reevaluated in 1985 . Posttrial mortality follow-up was continued up to December 31 , 1989 . SETTING Institute of Occupational Health , Helsinki , Finl and , and Second Department of Medicine , University of Helsinki . PARTICIPANTS In all , 3490 business executives born during 1919 through 1934 participated in health checkups in the late 1960s . In 1974 , 1222 of these men who were clinical ly healthy , but with CVD risk factors , were entered into the primary prevention trial ; 612 were r and omized to an intervention and 610 to a control group . INTERVENTIONS During the 5-year trial , the subjects of the intervention group visited the investigators every fourth month . They were treated with intensive dietetic-hygienic measures and frequently with hypolipidemic ( mainly clofibrate and /or probucol ) and antihypertensive ( mainly beta-blockers and /or diuretics ) drugs . The control group was not treated by the investigators . MAIN OUTCOME MEASURES Total mortality , cardiac mortality , mortality due to other causes . RESULTS Total coronary heart disease risk was reduced by 46 % in the intervention group as compared with the control group at end-trial . During 5 posttrial years , the risk factor and medication differences were largely leveled off between the groups . Between 1974 and 1989 the total number of deaths was 67 in the intervention group and 46 in the control group ( relative risk [ RR ] , 1.45 ; 95 % confidence interval [ CI ] , 1.01 to 2.08 ; P = .048 ) ; there were 34 and 14 cardiac deaths ( RR , 2.42 ; 95 % CI , 1.31 to 4.46 ; P = .001 ) , two and four deaths due to other CVD ( not significant ) , 13 and 21 deaths due to cancer ( RR , 0.62 ; 95 % CI , 0.31 to 1.22 ; P = .15 ) , and 13 and one deaths due to violence ( RR , 13.0 ; 95 % CI , 1.70 to 98.7 ; P = .002 ) , respectively . Multiple logistic regression analysis of treatments in the intervention group did not explain the 15-year excess cardiac mortality . CONCLUSION These unexpected results may not question multifactorial prevention as such but do support the need for research on the selection and interaction(s ) of methods used in the primary prevention of cardiovascular diseases", "The 4 year prospect i ve trial on the effectiveness of the antihypertensive treatment was performed in 100 mild hypertensive patients of the aged , the average age being 76.1 years . Dropouts during the drug-off control period were 9 cases . The matched pair group was selected by the age , sex , and blood pressure . Forty-four drug treated cases and 47 placebo treated cases were comparable in blood pressure as well as in laboratory data . Cerebrovascular and cardiac complications were observed in 4 cases or 10.5 % in the drug group , and in 9 cases or 22.0 % in the placebo group . When 8 cases of blood pressure elevation over 200/110 mmHg in the placebo group were added to the cardiovascular complications , dropouts in placebo group reached 41.5 % , and this showed the significant difference . Other complications were observed in 12 cases or 31.6 % in the drug group and in 17 cases or 41.5 % in the placebo group . Major complications were cancers , infections , and bone or joint diseases . Blood pressure was decreased from 171/87 to 151/80 in the drug group , and the average decrease was 20/7 mmHg in 4 year period . No significant changes in hematocrit , serum protein , urea nitrogen , uric acid , sodium , and potassium were observed during the trial period . The present study suggested that antihypertensive treatment was effective in the aged with mild hypertension , and that careful follow up was needed not only for cardiovascular complications but also for general health condition", "Angiotensin-converting enzyme inhibitors improve endothelial function , inhibit experimental atherogenesis , and decrease ischemic events . The Quinapril Ischemic Event Trial was design ed to test the hypothesis that quinapril 20 mg/day would reduce ischemic events ( the occurrence of cardiac death , resuscitated cardiac arrest , nonfatal myocardial infa rct ion , coronary artery bypass grafting , coronary angioplasty , or hospitalization for angina pectoris ) and the angiographic progression of coronary artery disease in patients without systolic left ventricular dysfunction . A total of 1,750 patients were r and omized to quinapril 20 mg/day or placebo and followed a mean of 27 + /- 0.3 months . The 38 % incidence of ischemic events was similar for both groups ( RR 1.04 ; 95 % confidence interval 0.89 to 1.22 ; p = 0.6 ) . There was also no significant difference in the incidence of patients having angiographic progression of coronary disease ( p = 0.71 ) . The rate of development of new coronary lesions was also similar in both groups ( p = 0.35 ) . However , there was a difference in the incidence of angioplasty for new ( previously unintervened ) vessels ( p = 0.018 ) . Quinapril was well tolerated in patients after angioplasty with normal left ventricular function . Quinapril 20 mg did not significantly affect the overall frequency of clinical outcomes or the progression of coronary atherosclerosis . However , the absence of the demonstrable effect of quinapril may be due to several limitations in study design", "BACKGROUND The efficacy of antihypertensive drugs newer than diuretics and beta-blockers has not been established . We compared the effects of the calcium-channel blocker nifedipine once daily with the diuretic combination co-amilozide on cardiovascular mortality and morbidity in high-risk patients with hypertension . METHODS We did a prospect i ve , r and omised , double-blind trial in Europe and Israel in 6321 patients aged 55 - 80 years with hypertension ( blood pressure > or = 150/95 mm Hg , or > or = 160 mm Hg systolic ) . Patients had at least one additional cardiovascular risk factor . We r and omly assigned patients nifedipine 30 mg in a long-acting gastrointestinal-transport-system ( GITS ) formulation ( n=3157 ) , or co-amilozide ( hydrochlorothiazide 25 mg [ corrected ] plus amiloride 2.5 mg ; n=3164 ) . Dose titration was by dose doubling , and addition of atenolol 25 - 50 mg or enalapril 5 - 10 mg . The primary outcome was cardiovascular death , myocardial infa rct ion , heart failure , or stroke . Analysis was done by intention to treat . FINDINGS Primary outcomes occurred in 200 ( 6.3 % ) patients in the nifedipine group and in 182 ( 5.8 % ) in the co-amilozide group ( 18.2 vs 16.5 events per 1000 patient-years ; relative risk 1.10 [ 95 % CI 0.91 - 1.34 ] , p=0.35 ) . Overall mean blood pressure fell from 173/99 mm Hg ( SD 14/8 ) to 138/82 mm Hg ( 12/7 ) . There was an 8 % excess of withdrawals from the nifedipine group because of peripheral oedema ( 725 vs 518 , p serious adverse events were more frequent in the co-amilozide group ( 880 vs 796 , p=0.02 ) . Deaths were mainly non-vascular ( nifedipine 176 vs co-amilozide 172 ; p=0.81 ) . 80 % of the primary events occurred in patients receiving r and omised treatment ( 157 nifedipine , 147 co-amilozide , difference 0.33 % [ -0.7 to 1.4 ] ) . INTERPRETATION Nifedipine once daily and co-amilozide were equally effective in preventing overall cardiovascular or cerebrovascular complications . The choice of drug can be decided by tolerability and blood-pressure response rather than long-term safety or efficacy", "BACKGROUND Microalbuminuria and hypertension are risk factors for diabetic nephropathy . Blockade of the renin-angiotensin system slows the progression to diabetic nephropathy in patients with type 1 diabetes , but similar data are lacking for hypertensive patients with type 2 diabetes . We evaluated the renoprotective effect of the angiotensin-II-receptor antagonist irbesartan in hypertensive patients with type 2 diabetes and microalbuminuria . METHODS A total of 590 hypertensive patients with type 2 diabetes and microalbuminuria were enrolled in this multinational , r and omized , double-blind , placebo-controlled study of irbesartan , at a dose of either 150 mg daily or 300 mg daily , and were followed for two years . The primary outcome was the time to the onset of diabetic nephropathy , defined by persistent albuminuria in overnight specimens , with a urinary albumin excretion rate that was greater than 200 microg per minute and at least 30 percent higher than the base-line level . RESULTS The base-line characteristics in the three groups were similar . Ten of the 194 patients in the 300-mg group ( 5.2 percent ) and 19 of the 195 patients in the 150-mg group ( 9.7 percent ) reached the primary end point , as compared with 30 of the 201 patients in the placebo group ( 14.9 percent ) ( hazard ratios , 0.30 [ 95 percent confidence interval , 0.14 to 0.61 ; P average blood pressure during the course of the study was 144/83 mm Hg in the placebo group , 143/83 mm Hg in the 150-mg group , and 141/83 mm Hg in the 300-mg group ( P=0.004 for the comparison of systolic blood pressure between the placebo group and the combined irbesartan groups ) . Serious adverse events were less frequent among the patients treated with irbesartan ( P=0.02 ) . CONCLUSIONS Irbesartan is renoprotective independently of its blood-pressure-lowering effect in patients with type 2 diabetes and microalbuminuria", "The purpose of this study was to evaluate the long-term safety and efficacy of moexipril , a non-sulphydryl angiotensin converting enzyme inhibitor , alone or in combination with hydrochlorothiazide in older patients with hypertension . One hundred and seventy two hypertensive men and women , 65 - 80 years old , with seated DBP between 95 and 114 mm Hg were studied . The study was a 2 year , multicentre ( 12 centres ) , open-label protocol of moexipril monotherapy or combination therapy ( with hydrochlorothiazide ) . Blood pressure , pulse rate , weight , adverse effects and laboratory studies were assessed following moexipril at 7.5 or 15 mg once daily or 7.5 or 15 mg daily in combination with 25 mg of hydrochlorothiazide if the seated DBP remained > or = 90 mm Hg on moexipril monotherapy . The primary measure of efficacy was a change from baseline in seated DBP . Secondary outcome measures included changes in seated DBP , pulse rate , laboratory parameters and adverse side-effects . Following 1 year of therapy in 135 patients , the BP fell 16/14 mm Hg among patients receiving moexipril monotherapy and 27/17 mm Hg for those receiving combined therapy compared with baseline ( P experiences . There were no significant changes in pulse rate or postural reductions in BP on either moexipril monotherapy or combination treatment . Three adverse side-effects occurred at a frequency exceeding 2 % that were possibly or probably attributable to moexipril or combination therapy : hypotension ( 2 % ) , dizziness ( 6 % ) and increased cough ( 12 % ) . There were no clinical ly relevant mean group changes from baseline laboratory values in the treatment groups . In conclusion , these long-term data demonstrate that moexipril , either alone or in combination with hydrochlorothiazide , has long-term anti-hypertensive efficacy and is generally well tolerated in elderly patients with hypertension", "Although limited numbers of elderly subjects have occasionally been included in population -based studies , only a few studies have been conducted specifically on elderly hypertensives , and practically none at a population level . We studied 655 hypertensive subjects from a cohort of 2,254 elderly subjects . The intervention consisted of the creation of a Hypertension Out patients ' Clinic under our auspices but with complete co-operation from general practitioners , r and omizing the identified hypertensive patients into pre-established therapeutic drug regimens , and early follow-up recording of mortality for 7 years . The drugs used were clonidine ( n = 61 ) , nifedipine ( n = 146 ) and the fixed combination of atenolol+chlorthalidone ( n = 144 ) ; 304 subjects underwent \" free therapy \" by their personal physicians without any special intervention . There were 1,404 normotensive subjects . Overall 7-year follow-up mortality was 34.9 % in the hypertensive subjects receiving \" free therapy \" , 22.5 % in those receiving \" special care \" , and 24.2 % in the normotensives . Cardiovascular mortality was respectively 23.7 % , 12.2 % , and 12.0 % . Overall and cardiovascular annual cumulative mortality were significantly lower in the > than in the > group . The fixed combination of atenolol and chlorthalidone reduced mortality below that of the normotensives , independent of other cardiovascular risk factors", "A r and omised trial of the treatment of hypertension in 884 patients aged 60 to 79 years at the onset showed a reduction of 18/11 mm Hg in blood pressure over a mean follow up period of 4.4 years . The principal antihypertensive agents were atenolol and bendrofluazide . There was a reduction in the rate of fatal stroke in the treatment group to 30 % of that in the control group ( 95 % confidence interval 11 - 84 % , p less than 0.025 ) . The rate of all strokes ( fatal and non-fatal ) in the treatment group was 58 % of that in the control group ( 95 % confidence interval 35 - 96 % , p less than 0.03 ) . The incidence of myocardial infa rct ion and total mortality was unaffected by treatment . Question naires completed by the patients and their relatives failed to identify any differences in symptoms that were likely to be due to treatment", "BACKGROUND Characteristics such as age and race are often cited as determinants of the response of blood pressure to specific antihypertensive agents , but this clinical ly important issue has not been examined in sufficiently large trials , involving all st and ard treatments , to determine the effect of such factors . METHODS In a r and omized , double-blind study at 15 clinics , we assigned 1292 men with diastolic blood pressures of 95 to 109 mm Hg , after a placebo washout period , to receive placebo or one of six drugs : hydrochlorothiazide ( 12.5 to 50 mg per day ) , atenolol ( 25 to 100 mg per day ) , captopril ( 25 to 100 mg per day ) , clonidine ( 0.2 to 0.6 mg per day ) , a sustained-release preparation of diltiazem ( 120 to 360 mg per day ) , or prazosin ( 4 to 20 mg per day ) . The drug doses were titrated to a goal of less than 90 mm Hg for maximal diastolic pressure , and the patients continued to receive therapy for at least one year . RESULTS The mean ( + /- SD ) age of the r and omized patients was 59 + /- 10 years , and 48 percent were black . The average blood pressure at base line was 152 + /- 14/99 + /- 3 mm Hg . Diltiazem therapy had the highest rate of success : 59 percent of the treated patients had reached the blood-pressure goal at the end of the titration phase and had a diastolic blood pressure of less than 95 mm Hg at one year . Atenolol was successful by this definition in 51 percent of the patients , clonidine in 50 percent , hydrochlorothiazide in 46 percent , captopril in 42 percent , and prazosin in 42 percent ; all these agents were superior to placebo ( success rate , 25 percent ) . Diltiazem ranked first for younger blacks ( ) and older blacks ( > or = 60 years ) , among whom the success rate was 64 percent , captopril for younger whites ( success rate , 55 percent ) , and atenolol for older whites ( 68 percent ) . Drug intolerance was more frequent with clonidine ( 14 percent ) and prazosin ( 12 percent ) than with the other drugs . CONCLUSIONS Among men , race and age have an important effect on the response to single-drug therapy for hypertension . In addition to cost and quality of life , these factors should be considered in the initial choice of a drug", "In 1972 - -1973 , 785 symptom-free men , aged 40 to 49 years , without target organ damage , with systolic blood pressures between 150 and 179 mm Hg and diastolic blood pressure below 110 mm Hg , were assigned at r and om to one of two groups : ( 406 to a drug treatment group and 379 to a control group ) for a five-year controlled drug treatment trial to evaluate the effect of therapy on cardiovascular complications . Drug treatment started with hydrochlorothiazide . If systolic blood pressure remained above 140 mm Hg and /or diastolic blood pressure above 90 mm Hg , alphamethyldopa was added . If there were side effects , methyldopa was replaced with propranolol . The control group was not given a placebo . The mean observation time was 66 months ( range 60 to 78 months ) . A difference in blood pressure between groups of about 17 mm Hg systolic and 10 mm Hg diastolic was maintained throughout the study . The study protocol had a rather low \" ethical \" blood pressure roof , 180 mm Hg systolic and /or 110 mm Hg diastolic . Seventeen percent of the control group had an increase in blood pressure above this level during the trial , and drug treatment was started . There was no effect on major cardiovascular morbidity comparing groups as established by r and omization , with 18 events in the treatment group and 20 events in the control group . There was no difference between the groups in total mortality and mortality from cardiovascular events . However , in the subgroups with diastolic blood pressure greater than or equal to 100 mm Hg before r and omization , there was a probable reduction in total morbidity from cardiovascular events in favor or the group receiving drug therapy , 7.6 and 16.4 percent events in the treated and control groups , respectively . Cerebrovascular events occurred only in the control group , 7 versus 0 . Two cases of fatal aortic aneurysms also occurred in the control group . Other \" pressure \" complications , such as marked left ventricular hypertrophy in the electrocardiogram and left ventricular failure , occurred only in the control group . However , regarding coronary heart disease , including sudden death , the incidence tended to be higher in the treated group , although it was not statistically significant . Only 13 men ( 1.7 percent ) failed to meet for regular examinations . At the end of the study these men were also followed up with regard to possible cardiovascular events", "Abstract Morbidity , mortality , and target organ function have been followed in a double-blind study of a predominantly Negro clinic population with mild to moderately severe hypertension over a 2-year period . Patients were placed r and omly on either hypotensive drug therapy ( reserpine , thiazide , guanethedine ) or matched placebos . There were 6 treatment failures among 45 patients in the treatment group and 19 failures among 42 patients in the placebo group . All but one of the failures in the placebo group improved or cleared upon early institution of appropriate hypertensive and supportive therapy . Abnormalities in carbohydrate metabolism and serum uric acid levels were found in patients receiving long-term thiazide therapy . Hypertensive disease in the Negro population of Baltimore is a serious , life-threatening condition . Our study provides evidence of the need for continuous close supervision , and the provision of organized teams devoted to the care , of such a population", "The main aim of the trial was to determine whether drug treatment of mild hypertension ( phase V diastolic pressure 90 - 109 mm Hg ) reduced the rates of stroke , of death due to hypertension , and of coronary events , in men and women aged 35 - 64 years . A total of 17,354 patients was recruited , and 85,572 patient-years of observation accrued . Patients were r and omly allocated at entry to take bendrofluazide or placebo , or propranolol or placebo . The stroke rate was reduced with treatment ( 60 strokes , vs 109 in the placebo groups ) , being 1.4 and 2.6 per 1,000 patient-years of observation , respectively ( p less than 0.01 ) , but overall rates of coronary events were not different ( 222 with treatment and 234 with placebos ) . The incidence of all cardiovascular events was reduced with treatment ( 286 events , vs 352 with placebos ; p less than 0.05 ) . For rates of mortality from all causes , treatment made no difference . Several post hoc analyses of subgroup results were performed . The all-cause mortality was reduced in men on treatment ( 157 deaths , vs 181 in placebo groups ) but increased in women on treatment ( 91 deaths , vs 72 with placebos ) ; this difference between the sexes was significant ( p = 0.05 ) . The reduction in stroke rate was greater with bendrofluazide than with propranolol ( p = 0.002 ) . The rate of strokes was reduced in both smokers and non-smokers taking bendrofluazide , but only in non-smokers taking propranolol ; this difference between the drugs was significant ( p = 0.03 ) . The coronary-event rate was not reduced by bendrofluazide , whatever the smoking habit , nor in smokers taking propranolol , but it was reduced in non-smokers taking propranolol . ( ABSTRACT TRUNCATED AT 250 WORDS", "Abstract Objective : To compare the effectiveness and tolerability of hydrochlorothiazide , atenolol , nitrendipine , and enalapril in patients with mild to moderate hypertension . Design : R and omised multicentre trial over 48 weeks with double blind comparison of treatments . Setting : 48 centres in four countries . Patients : 868 patients with essential hypertension ( diastolic blood pressure 95 - 120 mm Hg ) Interventions : Initial treatment ( step 1 ) consisted of 12.5 mg hydrochlorothiazide ( n=215 ) , 25 mg atenolol ( n=215 ) , 10 mg nitrendipine ( n=218 ) , or 5 mg enalapril ( n=220 ) once daily . If diastolic blood pressure was not reduced to : Blood pressure by means of an automatic device with repeated measurements . Results : After eight weeks the response rate for atenolol ( 63.7 % ) was significantly higher than for enalapril ( 50.0 % ) , hydrochlorothiazide ( 44.7 % ) , or nitrendipine ( 44.5 % ) . After one year atenolol was still more effective ( 48.0 % ) than hydrochlorothiazide ( 35.4 % ) and nitrendipine ( 32.9 % ) , but not significantly better than enalapril ( 42.7 % ) . The treatment related dropout rate was higher ( P nitrendipine group ( n=28 ) . Conclusions : There is no evidence of superiority for antihypertensive effectiveness or tolerability of the “ new ” classes of antihypertensives ( calcium channel blockers and angiotensin converting enzyme inhibitors ) . As these drugs are now widely used as treatment of first choice , our results further emphasise the need for studies confirming that they also reduce morbidity and mortality , as has been shown for diuretics and ß blockers . Key messages Calcium channel blockers and angiotensin converting enzyme inhibitors as initial monotherapy in the treatment of hypertension Reduction in mortality has been shown only with established ß blockers and diuretics Comparison of treatment with hydrochlorothiazide , atenolol , nitrendipine , and enalapril showed no superiority of the new drug classes Atenolol was the most effective drug , while nitrendipine showed the highest drop out rat Elderly patients respond better to hydrochlorothiazide and nitrendipine , and women better to enalapril , although in both subgroups the highest rate of response was with", "& NA ; Isolated systolic hypertension ( ISH ) is a definite risk factor for cardiovascular complications ( i.e. , cardiac failure , coronary artery disease , and stroke ) independent of diastolic elevation . The prevalence of ISH is estimated to be approximately 15‐20 % in the population above the age of 60 years , and increases with advancing age . The Systolic Hypertension in the Elderly ( SHELL ) study is planned to evaluate the efficacy and tolerability of lacidipine , matched with the diuretic chlorthalidone , in treatment of ISH in elderly hypertensive patients ( EHP ) . One hundred fifteen Italian centers will participate in the study . Fifty centers are associated with the Società Italiana di Geriatria Ospedaliera and 65 centers are departments of internal medicine or outpatient clinics for management of hypertension . A total of 4,800 patients will be enrolled in the trial . Two subprojects will consist of periodical echocardiographic evaluation and 24‐h ambulatory blood pressure monitoring . The primary end point of the SHELL study is the incidence of cardiovascular and cerebrovascular events in EHP with ISH , treated with either lacidipine or chlorthalidone . In particular , the SHELL trial is intended to determine whether lacidipine treatment will significantly reduce fatal myocardial events and total cardiovascular mortality ", "Background A common method of recruiting for r and omized trials is to send letters to potentially eligible patients inviting them to a screening appointment . In 3 consecutive UK studies the proportion attending from those invited fell from 49 % [ 1 ] in 1994 - 1997 and 42%[2 ] in 1998 - 2001 to 13 % at the beginning of an ongoing study in 2007 . Procedures were similar in the 3 trials except that in 2007 the Patient Information Leaflet ( PIL ) was enclosed with the invitation letter . In order to underst and whether the contents and /or style of invitation would explain the declining trend , 2 separate r and omized comparisons were undertaken during the recruitment for the ongoing study", "PREVALENCE OF HYPERTENSION IN ELDERLY JAPANESE PATIENTS : Data collected from post-mortem information at the Tokyo Metropolitan Geriatric Hospital showed that the overall prevalence of hypertension in Japanese patients aged over 60 years was 53 % ; one-third of these elderly hypertensives had isolated systolic hypertension . Isolated systolic and systolodiastolic hypertension were each associated with a similar degree of increased atherosclerosis and cardiovascular complications . In a placebo-controlled study antihypertensive treatment produced a reduction in withdrawal from treatment in elderly patients with mild hypertension . INTERIM TRIAL RESULTS : Some interim results have been obtained from a new trial which is currently under way in Japan , the National Intervention Cooperative Study for the Treatment of Elderly Hypertensives , a long-term study comparing the effects of a calcium antagonist ( nicardipine ) and a thiazide diuretic ( trichlormethiazide ) on cardiovascular complications in elderly patients with mild to moderate hypertension", "Background and Purpose : & bgr;‐Blockers prevent vascular events in patients after myocardial infa rct ion and lower blood pressure , the main risk factor for stroke . Hence , we assessed the effects of atenolol on the occurrence of death from vascular causes , stroke , or myocardial infa rct ion and on blood pressure in patients after a transient ischemic attack or nondisabling ischemic stroke . Methods : In a double‐blind , placebo‐controlled r and omized clinical trial we studied the occurrence of the outcome event death from vascular causes , nonfatal stroke , or nonfatal myocardial infa rct ion and the outcome event fatal or nonfatal stroke as well as blood pressure on follow‐up . A total of 1,473 aspirin‐treated patients with transient ischemic attack or nondisabling ischemic stroke were r and omized to 50 mg atenolol daily or placebo . The mean follow‐up was 2.6 years . Results : Patients on atenolol had a risk of 97/732 ( 13.3 % ) for the combined outcome event versus a risk of 95/741 ( 12.8 % ) for those on placebo ( adjusted hazard ratio , 1.00 ; 95 % confidence interval , 0.76‐1.33 ) . The adjusted hazard ratio for fatal or nonfatal stroke was 0.82 ( 95 % confidence interval , 0.57‐1.19 ) . More patients on & bgr;‐blocker ( 153 ) reported adverse effects than on placebo ( 103 ) . At the first follow‐up visit after r and omization ( median at 4 months ) systolic blood pressure in the atenolol group had dropped by 8.0 mm Hg compared with 2.2 mm Hg in the placebo group ( difference , 5.8 mm Hg ; 95 % confidence interval , 2.9‐8.6 mm Hg ) . For diastolic blood pressure this difference was 2.9 mm Hg ( 95 % confidence interval , 1.5‐4.4 mm Hg ) . Conclusions : Our data neither confirm nor rule out that atenolol prevents important vascular events in patients after transient ischemic attack or nondisabling ischemic stroke , given the modest effect on blood pressure , the restrictions in patient selection , and the limited number of patient‐years . ( Stroke 1993;24:543‐548", "BACKGROUND Drugs that inhibit the renin-angiotensin-aldosterone system benefit patients at risk for or with existing cardiovascular disease . However , evidence for this effect in Asian population s is scarce . We aim ed to investigate whether addition of an angiotensin receptor blocker , valsartan , to conventional cardiovascular treatment was effective in Japanese patients with cardiovascular disease . METHODS We initiated a multicentre , prospect i ve , r and omised controlled trial of 3081 Japanese patients , aged 20 - 79 years , ( mean 65 [ SD 10 ] years ) who were undergoing conventional treatment for hypertension , coronary heart disease , heart failure , or a combination of these disorders . In addition to conventional treatment , patients were assigned either to valsartan ( 40 - 160 mg per day ) or to other treatment without angiotensin receptor blockers . Our primary endpoint was a composite of cardiovascular morbidity and mortality . Analysis was by intention to treat . The study was registered at clintrials.gov with the identifier NCT00133328 . FINDINGS After a median follow-up of 3.1 years ( range 1 - 3.9 ) the primary endpoint was recorded in fewer individuals given valsartan than in controls ( 92 vs 149 ; absolute risk 21.3 vs 34.5 per 1000 patient years ; hazard ratio 0.61 , 95 % CI 0.47 - 0.79 , p=0.0002 ) . This difference was mainly attributable to fewer incidences of stroke and transient ischaemic attack ( 29 vs 48 ; 0.60 , 0.38 - 0.95 , p=0.028 ) , angina pectoris ( 19 vs 53 ; 0.35 , 0.20 - 0.58 , p heart failure ( 19 vs 36 ; 0.53 , 0.31 - 0.94 , p=0.029 ) in those given valsartan than in the control group . Mortality or tolerability did not differ between groups . INTERPRETATION The addition of valsartan to conventional treatment prevented more cardiovascular events than supplementary conventional treatment . These benefits can not be entirely explained by a difference in blood pressure control", "Background This long-term , multicenter , r and omized , double-blind , placebo-controlled , 2 × 2 factorial , angiographic trial evaluated the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis in normocholesterolemic patients . Methods and Results There were a total of 460 patients : 230 received simvastatin and 230 , a simvastatin placebo , and 229 received enalapril and 231 , an enalapril placebo ( some subjects received both drugs and some received a double placebo ) . Mean baseline measurements were as follows : cholesterol level , 5.20 mmol/L ; triglyceride level , 1.82 mmol/L ; HDL , 0.99 mmol/L ; and LDL , 3.36 mmol/L. Average follow-up was 47.8 months . Changes in quantitative coronary angiographic measures between simvastatin and placebo , respectively , were as follows : mean diameters , −0.07 versus −0.14 mm ( P = 0.004 ) ; minimum diameters , −0.09 versus −0.16 mm ( P = 0.0001 ) ; and percent diameter stenosis , 1.67 % versus 3.83 % ( P = 0.0003 ) . These benefits were not observed in patients on enalapril when compared with placebo . No additional benefits were seen in the group receiving both drugs . Simvastatin patients had less need for percutaneous transluminal coronary angioplasty ( 8 versus 21 events;P = 0.020 ) , and fewer enalapril patients experienced the combined end point of death/myocardial infa rct ion/stroke ( 16 versus 30;P = 0.043 ) than their respective placebo patients . Conclusions This trial extends the observation of the beneficial angiographic effects of lipid-lowering therapy to normocholesterolemic patients . The implication s of the neutral angiographic effects of angiotensin-converting enzyme inhibition are uncertain , but they deserve further investigation in light of the positive clinical benefits suggested here and seen elsewhere", "The present study of primary prevention in white men aged 40 to 64 years attempts to investigate whether a beta-blocker given as initial antihypertensive treatment would lower total mortality to a greater extent than thiazide diuretics . Patients were r and omized to metoprolol ( n = 1609 , 8110 patient-years ) or a thiazide diuretic ( n = 1625 , 8070 patient-years ) . The median follow-up time was 4.2 years . The mean dose of metoprolol was 174 mg/d , and of thiazide diuretics , 46 mg/d of hydrochlorothiazide or 4.4 mg/d of bendroflumethiazide . Identical control of blood pressure was achieved using a fixed therapeutic schedule . Total mortality was significantly lower for metoprolol than for thiazide diuretics because of fewer deaths from coronary heart disease and stroke . Total mortality was also significantly lower in smokers r and omized to metoprolol . The benefit demonstrated in patients treated with metoprolol seems to have important implication s for clinical practice", "The Hypertension Optimal Treatment ( HOT ) Study is an ongoing prospect i ve , r and omized , multicenter trial conducted in 26 countries . Its two main aims are to evaluate the relationship between three levels of target diastolic blood pressure ( incidence of cardiovascular morbidity and mortality in hypertensive patients and the effects on morbidity and mortality of a low dose , 75 mg daily , of acetylsalicylic acid ( ASA , aspirin ) compared with placebo . Altogether 19,193 patients have been recruited and r and omized and one-year data are now available for all patients . This is a report on the blood pressures achieved , the tolerability and other available data after 12 months of follow-up of all patients . Special reference will be given to the subgroup of elderly patients ( > or = 65 years , n = 6,113 ) as compared to younger patients ( On average , the target group diastolic blood pressure has reached 86 mmHg , the target group target blood pressures is 84 % in the target group elderly subgroup ( > or = 65 years of age ) the percentage of patients at target is higher for all target groups , being 86 , 76 and 61 % , respectively , at 12 months . Antihypertensive treatment is initiated with a calcium antagonist , felodipine , at a dose of 5 mg once daily . If target blood pressure is not reached , additional antihypertensive therapy , with either an angiotensin converting enzyme ( ACE ) inhibitor or a beta-adrenoceptor blocking agent , is given . Further dose adjustments are made in accordance with a set protocol . As a fifth and final step a diuretic may be added . Side effects have been relatively few in this large multinational series of intensively treated hypertensive patients . Only ankle edema , 2.6 % and 3.0 % , and coughing , 1.3 % and 0.8 % , in young and elderly patients , respectively , exceed a frequency of 1 % , and 88 % of all patients are still taking their baseline therapy felodipine after one year . The one-year data presented here indicate that it should be possible to fulfill the primary aims of the HOT Study", "Serum glucose levels , triglyceride levels , and body weight are reported from a controlled drug trial in men , aged 40 to 49 , with uncomplicated mild hypertension . The drug treatment started with hydrochlorothiazide alone , and methyldopa was added when necessary . If side effects occurred , methyldopa was replaced by propranolol . No detailed advice about diet , smoking , or weight reduction was given to any group . The untreated control subjects had a small increase in serum glucose levels during five years , from 6.08 to 6.21 mmol/liter . Those treated with hydrochlorothiazide alone and those treated with hydrochlorothiazide plus methyldopa had a small increase in serum glucose levels of the same order as that in the control subjects . However , those receiving the thiazide/propranolol combination experienced a sizeable increase in glucose levels , from 5.96 to 6.53 mmol/liter ( p less than 0.001 ) . This increase was significantly greater than the increase in the other groups ( p less than 0.001 ) . The thiazide/propranolol group also showed a significant increase in serum triglyceride levels ( p less than 0.05 ) . There was no difference in serum potassium levels in the different drug groups . The results indicate that moderate thiazide doses do not have significant effects on serum glucose levels in this age group . Propranolol in combination with thiazide seems to increase the level of serum glucose", "A feasibility trial to investigate the practicality of determining the advantages and disadvantages of prompt pharmacologic treatment for mild hypertension was jointly funded by the Veterans Administration and the National Heart , Lung and Blood Institute . Its clinical phase has been completed , and it demonstrated 1 . that the required relatively young asymptomatic population could be enrolled in the study and 2 . that it could be persuaded to adhere to the protocol for 2 years ; however , it was evident that intensive efforts would be required in both areas . The feasibility trial screened almost 120,000 potential subjects over a period of 16 months to r and omize about 1,000 subjects at four clinical centers . These men and women were 21 to 50 years old , had diastolic pressures from 85 to 105 mm Hg as out patients , and had no evidence of cardiovascular renal abnormalities . They were r and omized in double-blind fashion into active drug therapy and placebo groups . Stepped care therapy involved 50 mg chlorthalidone ( Step 1 ) , 100 mg chlorthalidone ( Step 2 ) and 100 chlorthalidone plus 0.25 mg reserpine ( Step 3 ) . Death , myocardial infa rct ion , stroke , angina pectoris , and congestive heart failure were the \" major \" morbid events that were looked for ; also recorded were \" minor \" morbid events consisting primarily of electrocardiographic arrhythmias . The development of significant hypertension was considered a treatment failure . Side effects were carefully tabulated in both active drug and placebo groups . The study revealed an average drop in diastolic pressure of almost 12 mm Hg for active drug group and less than half of that for the placebo group ; once established 6 months after r and omization , the new pressure levels persisted almost without change throughout the study . Although the feasibility trial was not design ed to answer the primary question regarding the benefits of treatment , the events were tabulated for each group . A total of 12 placebo-treated subjects developed significant hypertension and were put on active drug . There was not a significant difference between the two groups in the incidence of \" major \" morbid events ; a total of eight active and five placebo patients developed myocardial infa rct ion or died suddenly . There , however , was an excess of arrhythmias among the active drug subjects ( 17 in the active group versus 8 in the placebo group on the basis of preliminary data ) . Finally , there were twice as many side effects and 20 times as many chemical abnormalities among the active as among the placebo subjects . A protocol for a full scale study of the benefits of pharmacologic therapy in mild hypertensives has been prepared and is ready for implementation as needed ; it involves relatively minor modifications of the protocol tested in the feasibility trial", "OBJECTIVE To compare the rate of progression of mean maximum intimal-medial thickness ( IMT ) in carotid arteries , using quantitative B-mode ultrasound imaging , during antihypertensive therapy with isradipine vs hydrochlorothiazide . DESIGN R and omized , double-blind , positive-controlled trial . SETTING Nine medical center clinics . POPULATION A total of 883 patients with baseline mean + /- SD systolic and diastolic blood pressure ( SBP and DBP , respectively ) of 149.7 + /- 16.6 and 96.5 + /- 5.1 mm Hg , age of 58.5 + /- 8.5 years , and maximum IMT of 1.17 + /- 0.20 mm . INTERVENTIONS Twice daily doses of isradipine ( 2.5 - 5.0 mg ) or hydrochlorothiazide ( 12.5 - 25 mg ) . MAIN OUTCOME MEASURE ( PRIMARY END POINT ) : Rate of progression of mean maximum IMT in 12 carotid focal points over 3 years . RESULTS There was no difference in the rate of progression of mean maximum IMT between isradipine and hydrochlorothiazide over 3 years ( P=.68 ) . There was a higher incidence of major vascular events ( eg , myocardial infa rct ion , stroke , congestive heart failure , angina , and sudden death ) in isradipine ( n=25 ; 5.65 % ) vs hydrochlorothiazide ( n=14 ; 3.17 % ) ( P=.07 ) , and a significant increase in nonmajor vascular events and procedures ( eg , transient ischemic attack , dysrhythmia , aortic valve replacement , and femoral popliteal bypass graft ) in isradipine ( n=40 ; 9.05 % ) vs hydrochlorothiazide ( n=23 ; 5.22 % ) ( P=.02 ) . At 6 months , mean DBP decreased by 13.0 mm Hg in both groups , and mean SBP decreased by 19.5 mm Hg in hydrochlorothiazide and 16.0 mm Hg in isradipine ( P=.002 ) ; the difference in SBP between the 2 groups persisted throughout the study but did not explain the increased incidence of vascular events in patients treated with isradipine . CONCLUSION The rate of progression of mean maximum IMT in carotid arteries , the surrogate end point in this study , did not differ between the 2 treatment groups . The increased incidence of vascular events in patients receiving isradipine compared with hydrochlorothiazide is of concern and should be studied further", "OBJECTIVES To ascertain the baseline characteristics of the high-risk hypertensive patients entering the International Nifedipine GITS Study : Intervention as a Goal in Hypertension Treatment ( INSIGHT ) . To determine the success of single and combination therapy in achieving target blood pressures in such a population . DESIGN INSIGHT is a double-blind , prospect i ve outcome trial comparing the efficacy of the calcium channel blocker , nifedipine GITS , and the thiazide , co-amilozide , in preventing myocardial infa rct ion and stroke . We recruited 2996 men and 3454 women , aged 55 - 80 years , with blood pressure during placebo run-in > 150/95 mmHg or isolated systolic blood pressure > 160 mmHg from nine countries . Treatment allocation to nifedipine GITS 30 mg daily or co-amilozide ( hydrochlorothiazide 25 mg/amiloride 5 mg ) once daily was performed by minimization rather than r and omization to balance additional risk factors . This was followed by four optional increases in treatment : dose-doubling of the primary drug , addition of atenolol 25/50 mg or enalapril 5/10 mg , and then any other hypotensive drug excluding calcium blockers or diuretics . Target blood pressure was 140/90 mmHg or a fall > or = 20/10 mmHg . RESULTS Blood pressure at r and omization was 172+/-15 / 99+/-9 mmHg . Thirteen per cent of the patients were previously untreated . The proportions of each additional risk factors were : smoking > 10/day , 29 % ; cholesterol > 6.43 mmol/l , 52 % ; family history of premature myocardial infa rct ion or stroke , 21 % ; diabetes mellitus 20 % ; left ventricular hypertrophy , 10 % ; previous myocardial infa rct ion , other presentations of coronary heart disease , and peripheral vascular disease , each 6 % ; proteinuria , 3 % . Fifty-five per cent of patients had one additional risk factor , whereas 33 % , 9 % and 3 % had two , three or more additional risk factors , respectively . The blood pressure ( and falls in blood pressure ) at the end of titration and at 1 year after minimization was 139+/-12 / 82+/-7 mmHg ( 33+/-15 / 17+/-9 ) in the 5226 patients still on r and omized treatment The numbers requiring the four treatment increments were , respectively , 1591 , 780 , 597 and 294 , meaning that almost 70 % of patients on r and omized treatment in INSIGHT are receiving only the primary drug . At one year , 69 % of patients had a blood pressure blood pressure control in most patients without the addition of multiple additional treatments that may dilute any differences between the primary agents", "The objective of the study is to compare fatal and nonfatal cardiovascular endpoints in hypertensive patients r and omised to the calcium-channel blocker , nifedipine GITS or a thiazide diuretic , co-amilozide . A total of 6592 patients from nine countries ( UK , France , Israel , Spain , Italy , The Netherl and s , Sweden , Denmark and Norway ) will be recruited , aged 55 - 80 and with a blood pressure ( BP ) > or = 150/95 or > or = 160 mm Hg ( systolic ) . All patients will have at least one other major cardiovascular risk factor . Patients will be minimised by country and risk factors and r and omised to double-blind treatment with either nifedipine GITS or diuretic . After a single dose titration , additional treatment will be atenolol or enalapril ( where beta-blockade is contra-indicated ) . After achieving a target BP of 140/90 mm Hg patients will be followed for a total of 3 years . Primary endpoints are myocardial infa rct ion , stroke , subarachnoid haemorrhage , heart failure and sudden cardiac death . The study has a power of 80 % at 5 % significance to detect a difference between 8 % event rate over 3 years in diuretic-treated patients and 6 % in those receiving nifedipine", "Men aged 40 - 64 years with mild to moderate hypertension [ diastolic blood pressure ( DBP ) 100 - 130 mmHg ] were r and omized to treatment with a diuretic ( n = 3272 ) or a beta-blocker ( n = 3297 ) , with additional drugs if necessary , to determine whether a beta-blocker based treatment differs from thiazide diuretic based treatment with regard to the prevention of coronary heart disease ( CHD ) events and death . Patients with previous CHD , stroke or other serious diseases , or with contraindications to diuretics or beta-blockers were excluded . If normotension ( DBP less than 95 mmHg ) was not achieved by monotherapy , other antihypertensive drugs were added , but the two basic drugs were not crossed over . Patients were assessed at 6-monthly intervals . The mean follow-up for end-points was 45.1 months . Blood pressure ( BP ) side effects and end-points were recorded in a st and ardized manner . Entry characteristics and the BP reduction achieved were very similar in both treatment groups . All analyses were made on an intention-to-treat basis . The incidence of CHD did not differ between the two treatment groups . The incidence of fatal stroke tended to be lower in the beta-blocker treated group than in the diuretic treated group . Total mortality and the total number of end-points were similar in both groups . The percentage of patients withdrawn due to side effects was similar , whereas the number of reported symptoms , according to a question naire , was higher for patients on beta-blockers . The incidence of diabetes did not differ between the two groups . Subgroup analyses did not detect a difference in the effect of beta-blockers compared with diuretics in smokers as opposed to non-smokers , and beta-blockers also had the same effects as diuretics in the quartile with the highest predicted risk for CHD . Beta-blockers and thiazide diuretics were approximately equally well tolerated . The two drugs had a similar BP reducing effect although additional drugs had to be given more often in the diuretic group . Antihypertensive treatment based on a beta-blocker or on a thiazide diuretic could not be shown to affect the prevention of hypertensive complications , including CHD , to a different extent", "ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle – brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute C and esartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease : Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A R and omized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Sc and inavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Sc and inavian Cardiac Outcomes Trial — Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : C And esartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease — EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy C and esartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine – Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine – Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infa rct ion in 52 Countries INVEST : INternational VErapamil SR/T Tr and olapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention : an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : r and omized controlled trials RF : risk factor ROADMAP : R and omized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker C and esartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly : Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan R and omised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospect i ve Diabetes Study VADT : Veterans ' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization # # # 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension ( ESH ) and the European Society of Cardiology", "Hypertension is the most common condition seen in primary care and leads to myocardial infa rct ion , stroke , renal failure , and death if not detected early and treated appropriately . Patients want to be assured that blood pressure ( BP ) treatment will reduce their disease burden , while clinicians want guidance on hypertension management using the best scientific evidence . This report takes a rigorous , evidence -based approach to recommend treatment thresholds , goals , and medications in the management of hypertension in adults . Evidence was drawn from r and omized controlled trials , which represent the gold st and ard for determining efficacy and effectiveness . Evidence quality and recommendations were grade d based on their effect on important outcomes . There is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg ; however , there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal , or in those younger than 30 years for a diastolic goal , so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion . The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease ( CKD ) as for the general hypertensive population younger than 60 years . There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor , angiotensin receptor blocker , calcium channel blocker , or thiazide-type diuretic in the nonblack hypertensive population , including those with diabetes . In the black hypertensive population , including those with diabetes , a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy . There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes . Although this guideline provides evidence -based recommendations for the management of high BP and should meet the clinical needs of most patients , these recommendations are not a substitute for clinical judgment , and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient" ]	41188ace-06ff-11f0-808a-c43d1ab1c353
Purpose The purpose was to review relevant scientific papers written since 1989 which focused on the prevalence and management of dysgeusia as an oral side effect of cancer treatment . Methods Our literature search was limited to English language papers published between 1990 and 2008 . A total of 30 papers were review ed ; the results of 26 of these papers were included in the present systematic review . A structured assessment form was used by two review ers for each paper . Studies were weighted as to the quality of the study design , and treatment recommendations were based on the relative strength of each paper . Results A wide range in reported prevalence of dysgeusia was identified with the weighted prevalence from 56–76 % , depending on the type of cancer treatment . Attempts to prevent dysgeusia through the prophylactic use of zinc sulfate or amifostine have been of limited benefit . Nutritional counseling may be helpful to some patients in minimizing the symptoms of dysgeusia . Conclusions Dysgeusia is a common oral side effect of cancer therapy ( radiotherapy , chemotherapy , or combined modality therapy ) and often impacts negatively on quality of life . From the current literature , there does not appear to be a predictable way of preventing or treating dysgeusia	[ "BACKGROUND The aim of the study was to analyse the toxicity and health related quality of life ( HRQoL ) of breast cancer patients treated with FAC ( 5-fluorouracil , doxorubicin , cyclophosphamide ) and TAC ( docetaxel , doxorubicin , cyclophosphamide ) with and without primary prophylactic G-CSF ( PPG ) . PATIENTS AND METHODS This was a phase III study to compare FAC and TAC as adjuvant treatment of high-risk node-negative breast cancer patients . After the entry of the first 237 patients , the protocol was amended to include PPG in the TAC arm due to the high incidence of febrile neutropenia . A total of 1047 evaluable patients from 49 centres in Spain , two in Pol and and four in Germany were included in the trial . Side-effects and the scores of the EORTC QLQ-C30 and QLQ BR-23 question naires were compared in the three groups ( FAC , TAC pre-amendment and TAC post-amendment ) . RESULTS The addition of PPG to TAC significantly reduced the incidence of neutropenic fever , grade 2 - 4 anaemia , asthenia , anorexia , nail disorders , stomatitis , myalgia and dysgeusia . Patient QoL decreased during chemotherapy , more with TAC than FAC , but returned to baseline values afterwards . The addition of PPG to TAC significantly reduced the percentage of patients with clinical ly relevant Global Health Status deterioration ( 10 or more points over baseline value ) at the end of chemotherapy ( 64 % versus 46 % , P PPG significantly reduces the incidence of neutropenic fever associated with TAC chemotherapy as well as that of some TAC-induced haematological and extrahaematological side-effects . The HRQoL of patients treated with TAC is worse than that of those treated with FAC but improves with the addition of PPG , particularly in the final part of chemotherapy treatment", "BACKGROUND renal cell carcinoma ( RCC ) is a potential target for anti-angiogenic drugs because of its high vascularization . Neovastat ( AE-941 ) is an inhibitor of angiogenesis with a mechanism of action that could prove beneficial in the treatment of RCC . Patients and design A phase II trial was conducted to identify the long-term safety profile of Neovastat in advanced cancer patients and to obtain preliminary information on its efficacy in solid tumors refractory to st and ard treatments . Neovastat ( 60 or 240 ml/day ) was administered orally ( b.i.d . ) to 144 patients with solid tumors refractory to st and ard therapies or for whom no st and ard treatments were available . RESULTS A survival analysis was conducted on 22 patients with a primary diagnosis of refractory RCC to determine whether the dose of Neovastat had any effect . A significant relationship between dose and survival was observed ; the median survival time was significantly longer ( 16.3 versus 7.1 months ; P = 0.01 ) in patients treated with Neovastat 240 ml/day ( n = 14 ) compared with patients receiving 60 ml/day ( n = 8) . No dose-limiting toxicity was reported . The most frequent adverse event was taste alteration ( 13.6 % ) . CONCLUSIONS Neovastat is well tolerated by advanced cancer patients at doses of 60 and 240 ml/day . The higher dose of Neovastat administered in this trial is associated with a survival benefit in RCC , which is not explained by differences in major prognostic factors", "AMD473 is a novel sterically hindered platinum cytotoxic with demonstrated ability to overcome acquired resistance to cisplatin in vitro and in human tumour xenografts . A single-agent dose escalating Phase I study was performed . AMD473 was initially administered intravenously as a 1 h infusion every 21 days to patients with advanced solid tumours . In total , 42 patients received a total of 147 cycles ( median 3 , range 1–8 ) of treatment at doses of 12 , 24 , 48 , 96 , 110 , 120 , 130 , and 150 mg m−2 . Dosing intervals of 21 and 28 days were explored at the recommended dose . Neutropenia and thrombocytopenia proved dose limiting . Other toxicities included moderate nausea , vomiting , anorexia , and a transient metallic taste . There was no significant alopecia . The maximum tolerated dose was 150 mg m−2 . Plasma pharmacokinetics were linear . Two patients with heavily pretreated ovarian cancer showed partial response . Five patients ( mesothelioma , ovary , nonsmall cell lung , and melanoma ) showed prolonged stable disease . AMD473 demonstrates encouraging activity in patients , including those with prior platinum exposure . Toxicity is predictable with linear pharmacokinetics , as was predicted by pre clinical studies . A dose of 120 mg m−2 every 21 days is recommended for Phase II evaluation although there is evidence that chemo-naive patients and those of good performance status may tolerate a higher dose", "In the treatment of dysgeusia , the use of zinc has been frequently tried , with equivocal results . The aim of the present r and omized clinical trial , which involved a sufficiently large sample , was therefore to determine the efficacy of zinc treatment . Fifty patients with idiopathic dysgeusia were carefully selected . Zinc gluconate ( 140 mg/day ; n = 26 ) or placebo ( lactose ; n = 24 ) was r and omly assigned to the patients . The patients on zinc improved in terms of gustatory function ( p rated the dysgeusia as being less severe ( p signs of depression in the zinc group were less severe ( Beck Depression Inventory , p mood scale , p salivary calcium level , which was higher in the zinc patients ( p zinc appears to improve general gustatory function and , consequently , general mood scores in dysgeusia patients", "PURPOSE This prospect i ve , longitudinal study was aim ed to describe the prevalence , severity , and pattern of symptoms over the course of radiation therapy in persons with nasopharyngeal carcinoma and to explore symptom severity by treatment modality . DESCRIPTION OF STUDY Thirty-seven patients completed this study , and 46 % received chemotherapy before radiation therapy . A self-reported radiation symptom checklist and an objective mucositis assessment tool were used weekly to document oropharyngeal , skin , nose or ear , or more general side effects , and mucositis . RESULTS Oropharyngeal problems were the most severe complaints during radiation therapy . All patients experienced dry mouth , taste change , difficulty in swallowing , difficulty in opening their mouths , hoarseness , sore throat , and observable mucositis . Most reported moderate-to-severe dry mouth , difficulty in swallowing , and sore throat from weeks 3 through 7 . Skin problems were not prominent until week 4 . Patients also lost an average of 3.9 kg during the therapy . Sequential chemotherapy and radiation therapy was associated with more severe oropharyngeal problems than radiation therapy alone , but no significant differences in other problems were found . CLINICAL IMPLICATION S Despite recognition of the oropharyngeal side effects associated with irradiation , effective management protocol s for such symptoms have not been implemented in the studied institution . The frequency and intensity of the symptoms reported indicate an urgent need for increased vigilance about radiation-related side effects and pain management . As well , patient education about expected side effects may help mitigate the anxiety that patients experience when these symptoms occur", "INTRODUCTION Stage II nasopharyngeal carcinoma ( NPC ) treated with conventionally fractionated radiotherapy results in loco-regional control of around 80 % . This report aims to document the outcome of Stage II NPC patients treated with external beam radiotherapy delivered using an accelerated concomitant boost ( C-Boost ) schedule . METHODS AND MATERIAL S Twenty-five 1997 AJCC Stage II NPC patients were enrolled and analyzed in this preliminary report . The primary tumor and clinical ly involved nodes received a total dose of 72 Gy in 42 fractions . C-Boost for gross disease consisted of 18 Gy in 12 fractions commencing on day 19 and was delivered at least 6 hours after the first dose . Patients were assessed for response , survival , and toxicity . RESULTS With a median follow-up of 24 months , only one patient had pathologically confirmed local recurrence , necessitating IMRT . Two developed distant metastases for which they received chemotherapy . One died from systemic disease after refusing treatment for persistent neck lymphadenopathy . Two-year loco-regional control rates , overall survival and disease-free survival rates were 96 % , 96 % , and 88 % , respectively . All patients experienced some degree of acute and /or late toxicity . However , the toxicity profile was comparable to that seen following st and ard fractionation . Acute or late toxicities directly attributable to C-Boost were not observed . CONCLUSION This C-Boost radiotherapy regimen administers a substantially higher biologically effective dose compared with conventional radiation schedules . Preliminary locoregional control and survival rates are promising with no significant acute and /or late toxicities", "PURPOSE Smell and taste changes during chemotherapy are significant complaints of cancer patients . Loss of olfactory/gustatory function can lead to malnutrition , weight loss , and possibly a prolonged morbidity of chemotherapy-induced adverse effects , decreased quality of life , poor compliance , and even decreased therapy response . This prospect i ve study comprehensively investigated , to our knowledge for the first time , smell and taste changes in a cohort of 87 patients undergoing chemotherapy for breast cancer or gynecologic malignancies . PATIENTS AND METHODS Olfactory function was tested using Sniffin ' Sticks ( Burghart ; Wedel , Germany ) and gustatory function was tested using taste strips before , during , and immediately and 3 months after chemotherapy . RESULTS Olfactory and gustatory function significantly decreased during chemotherapy and recovered almost completely 3 months after chemotherapy . Scores of odor thresholds were affected more than those of discrimination or identification . The olfactory function of older patients was affected more than that of younger patients . There was no difference in the olfactory function during chemotherapy with respect to the chemotherapeutic agent or initial diagnosis ( breast or ovarian cancer ) . Regarding taste , scores of salty taste were affected more than scores of sweet , sour , or bitter taste . The gustatory function did not differ significantly during chemotherapy with respect to age or diagnosis but did differ with respect to the chemotherapeutic agent . Taxane-based chemotherapy caused the most severe disorders . CONCLUSION Chemotherapy has a significant but transient effect on olfactory and gustatory function , possibly causing reduced appetite , a low energy intake , and weight loss . Additional spices and flavoring may compensate for this diminished chemosensory function , enhancing patient compliance and quality of life", "BACKGROUND We aim ed to determine the effect of dietary counseling or oral supplements on outcome for patients with cancer , specifically , nutritional outcome , morbidity , and quality of life ( QOL ) , during and 3 months after radiotherapy . METHODS Seventy-five patients with head and neck cancer who were referred for radiotherapy ( RT ) were r and omized to the following groups : group 1 ( n = 25 ) , patients who received dietary counseling with regular foods ; group 2 ( n = 25 ) , patients who maintained usual diet plus supplements ; and group 3 ( n = 25 ) , patients who maintained intake ad lib . Nutritional intake ( determined by diet history ) and status ( determined by Ottery 's Subjective Global Assessment ) , and QOL ( determined by the European Organization for the Research and Treatment of Cancer Quality of Life Question naire version 3.0 [ EORTC QLQ-C30 ] ) were evaluated at baseline , at the end of RT , and at 3 months . RESULTS Energy intake after RT increased in both groups 1 and 2 ( p Protein intake also increased in both groups 1 and 2 ( p energy and protein intake decreased significantly in group 3 ( p 90 % of patients experienced RT toxicity ; this was not significantly different between groups , with a trend for reduced symptomatology in group 1 versus group 2/group 3 ( p reduction of incidence/severity of grade 1 + 2 anorexia , nausea/vomiting , xerostomia , and dysgeusia was different : 90 % of the patients improved in group 1 versus 67 % in group 2 versus 51 % in group 3 ( p QOL function scores improved ( p nutritional intake and status in group 1/group 2 ( p overall QOL , whereas patients in groups 2 and 3 maintained or worsened overall QOL . CONCLUSIONS During RT , nutritional interventions positively influenced outcomes , and counseling was of similar/higher benefit ; in the medium term , only counseling exerted a significant impact on patient outcomes", "Purpose : To determine the clinical , pathologic , and molecular effects of neoadjuvant docetaxel chemotherapy in high-risk localized prostate cancer . Experimental Design : Patients with biopsy Gleason scores of 8 to 10 , serum prostate-specific antigen levels > 20 ng/mL , and /or clinical stage T3 disease received weekly docetaxel ( 36 mg/m2 ) for 6 months , followed by radical prostatectomy , and were monitored with weekly visits , serum prostate-specific antigen measurements , and endorectal magnetic resonance imaging ( MRI ) . Frozen tumor specimens were collected for microarray analysis . Results : The 19 patients enrolled received 82 % of the planned chemotherapy . Toxicity was mild to moderate ; fatigue and taste disturbance were common . Prostate-specific antigen declines of > 50 % were seen in 11 of 19 patients ( 58 % ; 95 % confidence interval , 33 - 80 % ) and endorectal MRI showed maximum tumor volume reduction of at least 25 % in 13 of 19 patients ( 68 % ; 95 % confidence interval , 47 - 85 % ) and at least 50 % in 4 patients ( 21 % ; 95 % confidence interval , 6 - 46 % ) . Sixteen patients completed chemotherapy and had radical prostatectomy ; none achieved pathologic complete response . Microarray analysis identified coordinate up-regulation of genes involved in and rogen metabolism associated with docetaxel therapy . Specifically , RNA expression for genes that decrease cellular levels of bioactive and rogens was coordinately increased in response to chemotherapy . Conclusions : Neoadjuvant docetaxel administered for 6 months before radical prostatectomy is feasible , well tolerated , and often results in prostate-specific antigen declines of > 50 % and decreased tumor volume on endorectal MRI . No pathologic complete responses were observed . Altered and rogen metabolism may partially account for the noted declines in prostate-specific antigen and be a mechanism for chemotherapy resistance", "PURPOSE To determine the ability of amifostine to reduce the severity and /or incidence of the acute toxicities of concurrent chemotherapy and radiotherapy ( RT ) for non-small-cell lung cancer . METHODS AND MATERIAL S Patients with inoperable , nonmetastatic non-small-cell lung cancer receiving concurrent chemoradiotherapy were r and omized to one of two treatment groups . Arm 1 patients received thoracic RT ( total dose , 69.6 Gy in 58 fractions of 1.2 Gy b.i.d . 5 d/wk ) , plus oral etoposide ( 50 mg b.i.d . 30 min before thoracic RT for 10 days , repeated on Day 29 ) and cisplatin ( 50 mg/m2 i.v . on Days 1 , 8 , 29 , and 36 ) . Arm 2 patients received the same treatment plus amifostine ( 500 mg i.v . 20 - 30 min before any treatment the first 2 days of each week ) . Acute effects were assessed using the National Cancer Institute Common Toxicity Criteria . RESULTS Sixty-two patients were enrolled between November 1998 and January 2001 . The minimal follow-up was 24 months , and the median follow-up of living patients was 31 months . The patient and tumor characteristics were equally distributed between the patients in the two arms . The median survival time was 20 months in Arm 1 patients and 19 months in Arm 2 patients . The maximal esophageal toxicity was mild ( Grade 1 ) in 23 % , moderate ( Grade 2 ) in 42 % , and severe ( Grade 3 - 4 ) in 35 % of patients in Arm 1 ; the corresponding rates for the Arm 2 patients were 48 % , 35 % , and 16 % ( p = 0.021 ) . Severe pneumonitis occurred in 16 % of the Arm 1 and none of the Arm 2 patients ( p = 0.020 , chi-square test ) . Neutropenic fever occurred in 39 % of Arm 1 and 16 % of Arm 2 patients ( p = 0.046 , chi-square test ) . Mild hypotension , dysgeusia , and sneezing were significantly more frequent among the patients in Arm 2 . CONCLUSION Amifostine reduced the severity and incidence of acute esophageal , pulmonary , and hematologic toxicity result ing from concurrent cisplatin-based chemotherapy and RT . Amifostine had no apparent effect on survival in these patients with unresectable non-small-cell lung cancer , suggesting that it does not have a tumor-protective effect", "Abstract A r and omized study was conducted to evaluate the protective activity of amifostine ( A ) against the dose-limiting toxicities of radiochemotherapy ( RCT ) . Patients with head and neck cancer received radiotherapy ( 2 Gy/day 5 days a week up to 60 Gy ) with carboplatin 70 mg/m2 on days 1–5 and 21–25 inclusive . Patients either received RCT alone ( n=14 ) or RCT + A at a dose of 500 mg prior to treatment with carboplatin ( n=25 ) . There was a significant reduction in the incidence of grade 3/4 mucositis ( P acute grade 2 xerostomia ( P grade 3/4 thrombocytopenia ( P=0.012 ) in these patients who received A. The incidence of grade 2 late xerostomia at 12 months is 16.7 % and the incidence of loss of taste is 0 % in patients treated with A , as opposed to 54.5 % and 63.6 % in patients who received RCT alone . There were 18 ( 72 % ) complete responses ( CR ) and 6 ( 24 % ) partial responses ( PR ) in patients who received A , compared with 6 ( 43 % ) CR and 6 PR ( 43 % ) in patients treated with RCT alone . The disease-free survival at 12 months is 85.7 % in the RCT + A arm and 78.6 % in the RCT alone arm . The use of amifostine reduces the incidence and severity of acute and late toxicities associated with RCT whilst preserving antitumour activity", "PURPOSE / OBJECTIVES To determine the effectiveness of informational audiotapes on self-care behaviors , state anxiety , and use of self-care behaviors ; to describe the occurrence and intensity of common side effects in patients with breast cancer . DESIGN R and omized clinical trial . SETTING Outpatient chemotherapy clinics operated by a university center in a rural area . SAMPLE 70 women receiving their first treatment of chemotherapy . METHODS Subjects completed demographic data and the Spielberger State-Trait Anxiety instrument ( stai ) . The experimental group received two audiotapes . At one and three months , subjects completed the modified nail self-care diary and stai via telephone . MAIN RESEARCH VARIABLES State anxiety , side-effect severity , and use and efficacy of self-care behaviors . FINDINGS The most frequent side effects were fatigue , nausea and vomiting , and taste change . The experimental group reported symptom improvements that were not found in the control group . The experimental group increased the use of recommended self-care behaviors , whereas the control group continued to use the same self-care behaviors without effectiveness . State anxiety for both groups diminished over time ; however , anxiety in the control group was consistently higher . CONCLUSIONS Audiotapes are effective teaching tools . Self-care behaviors can be taught and can be effective in managing side effects . Anxiety was high in both groups , but the symptom decreased in the women who received audiotapes and telephone calls . IMPLICATION S FOR NURSING Constraints on nurses decrease the length of teaching time available , but audiotapes provide effective teaching and reinforcement of education . Anxiety in clinical environments interferes with patient learning . Teaching effective self-care behaviors enhances patients ' independence , comfort , control , and quality of life", "PURPOSE This study was design ed to investigate the quality of life ( QOL ) of patients enrolled onto the High-Dose Chemotherapy for Breast Cancer Study Group trial ( PEGASE 02 ) , a French pilot multicenter trial of the treatment of inflammatory breast cancer ( IBC ) aim ed at evaluating ( 1 ) toxicity and feasibility of sequential high-dose chemotherapy ( HDC ) with recombinant human granulocyte colony-stimulating factor ( filgrastim ) and stem-cell support and ( 2 ) response to HDC in terms of pathologic response and survival . PATIENTS AND METHODS QOL measures were performed at inclusion and four times subsequently up to 1 year using an ad hoc side-effect question naire ( 19 physical symptoms ) and the European Organization for Research and Treatment of Cancer Quality -of-Life Question naire ( EORTC QLQ-C30 ) . RESULTS Of the 95 patients entered , the overall QOL question naire completion compliance was 75.6 % . During cycle 3 of HDC , the number of symptoms was high ( mean + /- SD QOL score , 10 + /- 3 ) , with fatigue , hair loss , appetite loss , nausea , change in taste , vomiting , fever , and weight loss reported by more than 60 % of patients . Toxicity and distress associated with HDC were reflected in the decline of four EORTC QLQ-C30 scores : global QOL ( P = .001 ) , and physical , role , and social functioning ( P QOL deterioration disappeared after treatment completion , except for physical functioning ( P = .025 ) . One year after inclusion , most QOL scores returned to baseline , and both emotional functioning and global QOL scores were even higher than baseline ( P = .030 and P = .009 , respectively ) . CONCLUSION If it is confirmed that improvements in pathologic response rates with HDC effectively translate into increased probabilities of survival for IBC patients , adoption of such treatment as PEGASE 02 will not involve crucial choices between length of life and QOL and should not be delayed for QOL arguments", "PURPOSE The purpose of this study was to evaluate the feasibility , toxicity , and efficacy of a novel combined-modality treatment for patients with locally advanced squamous carcinoma of the head and neck . PATIENTS AND METHODS In this multicenter , community-based phase II study , 123 previously untreated patients with locally advanced squamous carcinoma of the head and neck received 6 weeks of induction chemotherapy followed by concurrent high-dose radiation therapy and weekly chemotherapy . Induction chemotherapy included paclitaxel ( 200 mg/m2 , 1-hour i.v . infusion ) on days 1 and 22 , carboplatin ( AUC 6.0 i.v . ) on days 1 and 22 , and 5-fluorouracil ( 225 mg/m2 per day , 24-hour continuous i.v . infusion ) on days 1–43 . After 1 week without therapy , radiation therapy , 1.8 Gy/day , 5 days weekly , to a total dose of 68.4 Gy , was administered to the primary site and the bilateral cervical lymph nodes . During radiation therapy , patients also received six weekly doses of paclitaxel ( 50 mg/m2 , 1-hour i.v . infusion ) and carboplatin ( AUC 1.0 i.v ) . After completion of therapy , patients were restaged with computed tomographic and endoscopic examination ; patients in complete remission were followed up without further treatment . RESULTS One hundred twenty-three patients ( 74 % with stage IV disease ) entered this trial , and 111 patients ( 90 % ) completed the entire treatment course . Seventy of 116 evaluable patients ( 60 % ; 95 % CI , 51%-69 % ) had a clinical complete response to treatment . After a median follow-up of 24 months , the 2- and 3-year actuarial survivals were 66 % and 51 % , respectively . Local toxicity was moderately severe during combined-modality therapy ; however , xerostomia has been the only frequent chronic toxicity of this program . CONCLUSIONS This novel combined-modality treatment program , containing paclitaxel and avoiding the use of cisplatin , is feasible , is highly active , and can be administered with acceptable toxicity in a community-based setting . Aggressive nutritional support should be considered in patients receiving this regimen , to improve acute palliation and to maximize the delivery of combined-modality therapy . Further evaluation of this treatment program is warranted . Incorporation of various novel biologic agents , particularly the epidermal growth factor receptor antagonists , may further improve efficacy ", "PURPOSE Taste alterations ( dysgeusia ) are well described in head and neck cancer patients who undergo radiotherapy ( RT ) . Anecdotal observations and pilot studies have suggested zinc may mitigate these symptoms . This multi-institutional , double-blind , placebo-controlled trial was conducted to provide definitive evidence of this mineral 's palliative efficacy . METHODS AND MATERIAL S A total of 169 evaluable patients were r and omly assigned to zinc sulfate 45 mg orally three times daily vs. placebo . Treatment was to be given throughout RT and for 1 month after . All patients were scheduled to receive > or = 2,000 cGy of external beam RT to > or = 30 % of the oral cavity , were able to take oral medication , and had no oral thrush at study entry . Changes in taste were assessed using the previously vali date d Wickham question naire . RESULTS At baseline , the groups were comparable in age , gender , and planned radiation dose ( or = 6,000 cGy ) . Overall , 61 zinc-treated ( 73 % ) and 71 placebo-exposed ( 84 % ) patients described taste alterations during the first 2 months ( p = 0.16 ) . The median interval to taste alterations was 2.3 vs. 1.6 weeks in the zinc-treated and placebo-exposed patients , respectively ( p = 0.09 ) . The reported taste alterations included the absence of any taste ( 16 % ) , bitter taste ( 8 % ) , salty taste ( 5 % ) , sour taste ( 4 % ) , sweet taste ( 5 % ) , and the presence of a metallic taste ( 10 % ) , as well as other descriptions provided by a write in response ( 81 % ) . Zinc sulfate did not favorably affect the interval to taste recovery . CONCLUSION Zinc sulfate , as prescribed in this trial , did not prevent taste alterations in cancer patients who were undergoing RT to the oral pharynx", "OBJECTIVES Laser-scanning microscopy ( LSM ) was used to compare taste buds and epithelia of fungiform papillae of healthy subjects with those of patients suffering from taste disorders during/after radiochemotherapy ( RCT ) . Aim of the study was to investigate effects responsible for taste loss at a microscopic level . STUDY DESIGN Prospect i ve study . METHODS Data from 12 healthy subjects ( mean age 52.4 , SD 9.5 years ) were compared with those of 12 patients ( mean age 54.7 , SD 8.5 years ) with head and neck cancer suffering from taste disorders during RCT . Four parameters from LSM were selected for analysis : 1 ) distance between the pore of the taste buds of fungiform papillae and the crest of the papillary vessels ; 2 ) epithelial cells of each taste bud at 34 mum ; 3 ) , cell density , and 4 ) area of the taste pore at 4 mum . These data were correlated to measures of gustatory sensitivity obtained with both the vali date d \" taste strips \" test kit and electrogustometry . RESULTS Patients complaining from taste disorders during RCT exhibited a significant decrease of taste function assessed with both natural and electric stimuli . In these patients , we found thicker epithelia and smaller areas of the taste pores compared with healthy subjects . In 30 % of those patients , no taste pores were detectable ; in deeper sections , however , normal taste buds were present . CONCLUSIONS In conclusion , in RCT patients with taste disorders , LSM indicates changes of epithelia of fungiform papilla but no changes of the taste bud structure . Damage of the chorda tympani nerve by scattered rays , direct or indirect mucotoxic effects of chemotherapeutic agents , and covering of taste pores by epithelial cells are likely reasons for taste loss during RCT", "PURPOSE To prospect ively assess 5-year late toxicity in patients treated by concomitant radiochemotherapy for locally advanced oropharynx carcinoma using three different toxicity scales . METHODS AND MATERIAL S A total of 226 patients were entered in a Phase III multicenter , r and omized trial comparing radiotherapy alone ( 70 Gy in 35 fractions : Arm A ) with concomitant radiochemotherapy ( 70 Gy in 35 fractions with three cycles of a 4-day regimen containing carboplatin and 5-fluorouracil : Arm B ) . Five living patients , free of local or distant recurrences , could not be evaluated for late toxicity . Forty-four patients were eligible for late toxicity with a median follow-up of 5 years . Late toxicity was evaluated by the radiation oncologist using a large question naire containing 120 mixed items of three scales ( NCI-CTC , LENT/SOMA , and RTOG ) . The data were then transposed on separate scales using corresponding grade s. RESULTS The 5-year overall survival rate was 22 % in Arm B and 16 % in Arm A ( p = 0.05 ) . The 5-year locoregional control rate was 48 % in Arm B and 25 % in Arm A ( p = 0.002 ) . The spinal cord was not affected by the concomitant adjunct of chemotherapy , and no deaths were caused by late toxicity . Using the three late toxicity scales , 100 % of the patients treated with the combined modality ( Arm B ) developed one or more late complications vs. 94 % in the radiotherapy-alone arm ( Arm A ) . The difference was not statistically significant . The most commonly damaged organs ( all Grade 1 - 4 ) were the salivary gl and s ( 100 % in Arm B vs. 82 % in Arm A , p skin ( 78 % vs. 47 % , p teeth ( 67 % vs. 18 % , p mucosa ( 59 % vs. 63 % p = not significant ) , and m and ible ( 44 % vs. 12 % , p Grade 3 - 4 complications occurred in 82 % of the patients in Arm B vs. 47 % in Arm A ( p = 0.02 ) but concerned only the teeth . The correlation between the RTOG and LENT/SOMA scale and between the NCI-CTC and LENT/SOMA scale were low for Grade 1 - 4 toxicity ( near 30 % ) . The transposability of a patient 's symptoms was significantly greater using the LENT/SOMA or RTOG/EORTC scaling systems than using the NCI-CTC system . CONCLUSION Concomitant radiochemotherapy increased overall survival and locoregional control rates . The difference between the two treatment groups for Grade 3 - 4 complications was only significant for the teeth . The late toxicity assessment of a treatment may depend on the toxicity scale used . The LENT/SOMA scale seems to be the most accurate scale , but most of the score results were not concordant with those obtained with other scales . The results of this study confirm the necessity of using a common late toxicity scale in clinical trials" ]	41188b0a-06ff-11f0-808a-c43d1ab1c353
Since August 2009 , members of the Primary Care Dentistry Research Forum ( www.dentistry research .org ) have taken part in an online vote to identify questions in day-to-day practice that they felt most needed to be answered with conclusive research . The question that receives the most votes each month forms the subject of a critical appraisal of the relevant literature . Each month a new round of voting takes place to decide which further questions will be review ed . Dental practitioners and dental care professionals are encouraged to take part in the voting and su bmi t their own questions to be included in the vote by joining the website . The paper below details a summary of the findings of the ninth critical appraisal . In order to address the question raised by dentistry research forum , first a search was conducted for systematic review s on the topic . There was one systematic review retrieved comparing bonded amalgam restorations versus non-bonded amalgam restorations . However , there was no other systematic review identified assessing the effectiveness of dental liners under amalgam restorations in general . Therefore , a search was conducted for any r and omised controlled trial ( RCT ) comparing use of a lining under amalgam restorations versus no lining or RCTs comparing differing lining material s under amalgam against each other . There were eight relevant RCTs identified . Due to the low quality , small sample sizes or lack of adequate reporting of the outcome data , the evidence is inadequate to cl aim or refute a difference in postoperative sensitivity between different dental liners . Further well-conducted RCTs are needed to answer this question . These RCTs would be preferably included and synthesis ed in a systematic review	[ "PURPOSE To compare the in vivo short-term post-operative sensitivity of teeth restored with amalgam using a bonded resin liner vs. teeth restored using a copal varnish liner . MATERIAL S AND METHODS 20 patients received Class I or Class II contralaterally paired restorations which were placed at the same appointment . All restorations were placed by the same operator using an identical technique except that , in each r and omized pair , one was lined with an adhesive resin ( Scotchbond Multi- Purpose Plus ) while the other was lined with copal varnish . ( Plastodent ) Patients were provided visual analog scale response forms , instructed in their use , and requested to complete and return a form reporting their degree of sensitivity at baseline and on days 1 , 3 , 7 , 14 , and 30 post-operatively . Data from the response forms were analyzed for differences using a paired t-test . RESULTS A response rate of 90 % ( 18/20 ) was achieved for the complete 30-day assessment . Increases in thermal sensitivity beyond baseline were seen in 13 of the 18 subjects involving 12 restorations lined with copal varnish and 10 lined with adhesive resin . Typically , sensitivity peaked on day 1 or day 3 and diminished to pre-operative levels by day 30 . Only three subjects reported greater sensitivity at day 30 than at baseline . No significant difference in post-operative sensitivity was found between the two cavity lining material s at any post-operative interval", "AIM The aim of this r and omized , double blind clinical trial was to compare three lining material s ( Adper Prompt L-Pop , VivaSens , and Copalite ) versus unlined restorations on postoperative cold sensitivity of class I amalgam restorations . METHODS AND MATERIAL S Potential subjects were screened for the presence of four initial class I carious lesions on posterior teeth . Each tooth was assigned to treatments according to a r and omized block design . After cavity preparation , teeth were lined with either VivaSens , Adper Prompt L-Pop , or Copalite , and one tooth remained unlined and served as a control . The cavities were filled with high copper amalgam ( Oralloy ) . The time taken for a subject to respond to a st and ardized cold stimulus ( CRM ) was recorded at baseline , 24 hours , one week , and one month after treatment . Participants filled out a self-report question naire at each time point . Data was gathered by analysis of variance ( ANOVA ) and Duncan Multiple Comparisons tests ( alpha=0.05 ) . RESULTS Twenty subjects participated in this study . Comparisons within each group found no significant reduction in mean CRM for the Adper Prompt L-Pop group ( P>0.05 ) , but a significant difference in mean CRM for the VivaSens group was observed at one week and one month intervals after restoration ( P mean CRM reductions after one day ( P Adper Prompt L-Pop and Copalite were found at any time point ( P>0.05 ) . VivaSens showed more cold sensitivity than Adper Prompt L-Pop at one week and one month recalls ( P cold sensitivity was found in the unlined group . CONCLUSION Adper Prompt L-Pop and Copalite reduced postoperative sensitivity to cold more than VivaSens and unlined groups at all assessment time points , 24 hours , one week , and one-month post treatment . The subjects receiving Copalite , VivaSens , and unlined restorations experienced greater sensitivity to cold at one month compared to baseline , while subjects receiving the Adper Prompt L-Pop liner experienced no greater sensitivity to cold from baseline to one month . CLINICAL SIGNIFICANCE Adper Prompt L-Pop as a liner under spherical high copper amalgam successfully reduced cold postoperative sensitivity", "The authors investigated the capability of two commonly used basing techniques to reduce postoperative sensitivity . The authors measured the time it took the subjects to respond to a st and ardized stimulus of cold water ( cold response measure , or CRM ) at baseline and one week after treatment . The authors found no significant reduction in the mean CRM for the group receiving Amalgambond Plus ( Parkell ) , but they did find a significant decrease in the mean CRM for the group receiving Copalite ( Harry J. Bosworth Co. ) with or without Vitrebond ( 3 M ) . The authors concluded that the subjects in the Amalgambond Plus group experienced no more sensitivity to cold at one week postoperative than they did at baseline , while the subjects in the Copalite/Vitrebond group did", "BACKGROUND This study was design ed to compare 2 % sodium fluoride ( NaF ) iontophoresis with other cavity liners . MATERIAL S AND METHODS This study was carried out in 30 patients in the age group 10 - 14 years with bilateral carious permanent first molars . The study evaluated the use of 2 % NaF iontophoresis as a cavity liner and also compared its desensitizing effect with varnish and an adhesive bonded liner . Sensitivity gradings were done on a subjective verbal rating scale . RESULTS All the liner treatments decreased the sensitivity following liner application . However , decrease of sensitivity in the case of 2 % NaF iontophoresis was more compared with that of varnish and adhesive bonded liner . The results were statistically significant . CONCLUSIONS It was found that 2 % NaF iontophoresis was more effective in reducing the postoperative sensitivity compared with that of varnish and scotchbond multi purpose", " This clinical study evaluated the microleakage effectiveness of a cavity varnish when used in combination with two types of amalgam : a spherical particle and a dispersed phase alloy . Calcium hydroxide was utilized as the microleakage detection agent . Copalite showed a reduction in microleakage when it was employed with the spherical particle alloy used in this study . This study clinical ly demonstrated that Copalite is not totally effective in eliminating microleakage", "OBJECTIVE The purpose of this clinical study was to assess the sensitivity experienced and reported by patients following treatment of primary carious lesions with Class I or Class II amalgam restorations . METHOD AND MATERIAL S Only previously untreated teeth were selected . The cavity preparations were treated according to one of four regimens : group 1 = no liner ; group 2 = two coats of a copal varnish ; group 3 = a dentin adhesive resin liner ; group 4 = a resin-modified glass-ionomer liner . Patients were contacted on days 2 and 7 postoperatively and question ed regarding the presence or absence of sensitivity . If sensitivity was experienced , they were asked which stimuli created the sensitivity , the length of time it lasted , and its intensity on a subjective scale . If sensitivity was experienced on day 7 , patients were also contacted on days 14 , 30 , and 90 to assess the degree of sensitivity . Nineteen teeth were included in each of the four groups . RESULTS By days 2 and 7 , no significant difference existed among groups ; by day 14 , 22 % of restorations in group 2 and 17 % of those in group 3 were sensitive , while teeth in groups 1 and 4 exhibited no sensitivity reactions . CONCLUSION Use of a resin-modified glass-ionomer liner or no dentin treatment result ed in short-term sensitivity in fewer than one third of the teeth . Almost one third of the teeth restored with a dentin adhesive resin liner or copal varnish exhibited initial sensitivity , which lasted up to 30 days in a few teeth", "Sixty subjects were r and omized into two groups . The time , in seconds , that it took subjects to respond to a st and ardized cold stimulus was recorded at baseline and again 1 week following treatment . During the intervening week subjects filled out three self-report question naires about pain from exposure to cold and several other common sources of postoperative pain . These question naires were filled out after 1 day , again 3 days after the first question naire , and 3 days after the second . Subjects mailed the question naires in immediately to provide three independent reports about cold sensitivity . The group receiving an OptiBond adhesive liner under their amalgam restorations was not found to be any less sensitive to cold , either by timed response to a cold stimulus or by self-report of pain , than the group receiving conventional liners and bases" ]	41188c54-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Vitamin D and related compounds have been used to prevent osteoporotic fractures in older people . This is the third up date of a Cochrane review first published in 1996 . OBJECTIVES To determine the effects of vitamin D or related compounds , with or without calcium , for preventing fractures in post-menopausal women and older men . SEARCH METHODS We search ed the Cochrane Bone , Joint and Muscle Trauma Group Specialised Register ( to December 2012 ) , the Cochrane Central Register of Controlled Trials ( 2012 , Issue 12 ) , MEDLINE ( 1966 to November Week 3 2012 ) , EMBASE ( 1980 to 2012 Week 50 ) , CINAHL ( 1982 to December 2012 ) , BIOSIS ( 1985 to 3 January 2013 ) , Current Controlled Trials ( December 2012 ) and reference lists of articles . SELECTION CRITERIA R and omised or quasi-r and omised trials that compared vitamin D or related compounds , alone or with calcium , against placebo , no intervention or calcium alone , and that reported fracture outcomes in older people . The primary outcome was hip fracture . DATA COLLECTION AND ANALYSIS Two authors independently assessed trial risk of selection bias and aspects of method ological quality , and extracted data . Data were pooled , where possible , using the fixed-effect model , or the r and om-effects model when heterogeneity between studies appeared substantial . MAIN RESULTS We included 53 trials with a total of 91,791 participants . Thirty-one trials , with sample sizes ranging from 70 to 36,282 participants , examined vitamin D ( including 25-hydroxy vitamin D ) with or without calcium in the prevention of fractures in community , nursing home or hospital inpatient population s. Twelve of these 31 trials had participants with a mean or median age of 80 years or over . Another group of 22 smaller trials examined calcitriol or alfacalcidol ( 1-alphahydroxyvitamin D3 ) , mostly with participants who had established osteoporosis . These trials were carried out in the setting of institutional referral clinics or hospitals . In the assessment of risk of bias for r and om sequence generation , 21 trials ( 40 % ) were deemed to be at low risk , 28 trials ( 53 % ) at unclear risk and four trials at high risk ( 8 % ) . For allocation concealment , 22 trials were at low risk ( 42 % ) , 29 trials were at unclear risk ( 55 % ) and two trials were at high risk (4%).There is high quality evidence that vitamin D alone , in the formats and doses tested , is unlikely to be effective in preventing hip fracture ( 11 trials , 27,693 participants ; risk ratio ( RR ) 1.12 , 95 % confidence intervals ( CI ) 0.98 to 1.29 ) or any new fracture ( 15 trials , 28,271 participants ; RR 1.03 , 95 % CI 0.96 to 1.11).There is high quality evidence that vitamin D plus calcium results in a small reduction in hip fracture risk ( nine trials , 49,853 participants ; RR 0.84 , 95 % confidence interval ( CI ) 0.74 to 0.96 ; P value 0.01 ) . In low-risk population s ( residents in the community : with an estimated eight hip fractures per 1000 per year ) , this equates to one fewer hip fracture per 1000 older adults per year ( 95 % CI 0 to 2 ) . In high risk population s ( residents in institutions : with an estimated 54 hip fractures per 1000 per year ) , this equates to nine fewer hip fractures per 1000 older adults per year ( 95 % CI 2 to 14 ) . There is high quality evidence that vitamin D plus calcium is associated with a statistically significant reduction in incidence of new non-vertebral fractures . However , there is only moderate quality evidence of an absence of a statistically significant preventive effect on clinical vertebral fractures . There is high quality evidence that vitamin D plus calcium reduces the risk of any type of fracture ( 10 trials , 49,976 participants ; RR 0.95 , 95 % CI 0.90 to 0.99).In terms of the results for adverse effects : mortality was not adversely affected by either vitamin D or vitamin D plus calcium supplementation ( 29 trials , 71,032 participants , RR 0.97 , 95 % CI 0.93 to 1.01 ) . Hypercalcaemia , which was usually mild ( 2.6 to 2.8 mmol/L ) , was more common in people receiving vitamin D or an analogue , with or without calcium ( 21 trials , 17,124 participants , RR 2.28 , 95 % CI 1.57 to 3.31 ) , especially for calcitriol ( four trials , 988 participants , RR 4.41 , 95 % CI 2.14 to 9.09 ) , than in people receiving placebo or control . There was also a small increased risk of gastrointestinal symptoms ( 15 trials , 47,761 participants , RR 1.04 , 95 % CI 1.00 to 1.08 ) , especially for calcium plus vitamin D ( four trials , 40,524 participants , RR 1.05 , 95 % CI 1.01 to 1.09 ) , and a significant increase in renal disease ( 11 trials , 46,548 participants , RR 1.16 , 95 % CI 1.02 to 1.33 ) . Other systematic review s have found an increased association of myocardial infa rct ion with supplemental calcium ; and evidence of increased myocardial infa rct ion and stroke , but decreased cancer , with supplemental calcium plus vitamin D , without an overall effect on mortality . AUTHORS ' CONCLUSIONS Vitamin D alone is unlikely to prevent fractures in the doses and formulations tested so far in older people . Supplements of vitamin D and calcium may prevent hip or any type of fracture . There was a small but significant increase in gastrointestinal symptoms and renal disease associated with vitamin D and calcium . This review found that there was no increased risk of death from taking calcium and vitamin	[ "Vitamin D insufficiency and low calcium intake contribute to increase parathyroid function and bone fragility in elderly people . Calcium and vitamin D supplements can reverse secondary hyperparathyroidism thus preventing hip fractures , as proved by Decalyos I. Decalyos II is a 2-year , multicenter , r and omized , double-masked , placebo-controlled confirmatory study . The intention-to-treat population consisted of 583 ambulatory institutionalized women ( mean age 85.2 years , SD = 7.1 ) r and omized to the calcium – vitamin D3 fixed combination group ( n= 199 ) ; the calcium plus vitamin D3 separate combination group ( n= 190 ) and the placebo group ( n= 194 ) . Fixed and separate combination groups received the same daily amount of calcium ( 1200 mg ) and vitamin D3 ( 800 IU ) , which had similar pharmacodynamic effects . Both types of calcium-vitamin D3 regimens increased serum 25-hydroxyvitamin D and decreased serum intact parathyroid hormone to a similar extent , with levels returning within the normal range after 6 months . In a subgroup of 114 patients , femoral neck bone mineral density ( BMD ) decreased in the placebo group ( mean = –2.36 % per year , SD = 4.92 ) , while remaining unchanged in women treated with calcium-vitamin D3 ( mean = 0.29 % per year , SD = 8.63 ) . The difference between the two groups was 2.65 % ( 95 % CI = –0.44 , 5.75 % ) with a trend in favor of the active treatment group . No significant difference between groups was found for changes in distal radius BMD and quantitative ultrasonic parameters at the os calcis . The relative risk ( RR ) of HF in the placebo group compared with the active treatment group was 1.69 ( 95 % CI = 0.96 , 3.0 ) , which is similar to that found in Decalyos I ( RR = 1.7 ; 95 % CI = 1.0 , 2.8 ) . Thus , these data are in agreement with those of Decalyos I and indicate that calcium and vitamin D3 in combination reverse senile secondary hyperparathyroidism and reduce both hip bone loss and the risk of hip fracture in elderly institutionalized women", "OBJECTIVES A high prevalence of hip and other fractures in elderly patients with Parkinson ’s disease has been linked to reduced bone mass arising from a defect of renal synthesis of 1 , 25-dihydroxyvitamin D ( 1 , 25-[OH]2D ) . Treatment with 1α-hydroxyvitamin D3 ( 1α(OH)D3 ; an active form of vitamin D ) was evaluated for maintaining bone mass and reducing the incidence of hip and other non-vertebral fractures in patients with Parkinson ’s disease . METHODS In a double blind , r and omised trial , 86 elderly patients with Parkinson ’s disease ( mean Hoehn and Yahr stage , 3 ; mean age 70.6 years ) were r and omised to receive either 1 μg 1α(OH)D3 daily ( treatment group , n=43 ) or a placebo ( n=43 ) for 18 months . Bone mineral densities in the second metacarpals were determined by computed radiographic densitometry . Serum bone turnover indices were measured serially , and incidence of non-vertebral fractures was recorded . RESULTS Bone mineral densities decreased 1.2 % in the treatment group compared with 6.7 % in the placebo group during 18 months ( p groups , the serum concentration of 1 , 25-[OH]2D was reduced . Parathyroid hormone was abnormally increased in 15 patients ( 17 % ) and correlated negatively with serum 25-hydroxyvitamin D , indicating compensatory hyperparathyroidism . Eight patients sustained fractures ( six at the hip and two at other sites ) in the placebo group , and one hip fracture occurred among treated patients ( odds ratio 9.8 ; p=0.0028 ) . CONCLUSION By increasing serum 1 , 25-[OH]2D concentrations , treatment with 1α(OH)D3 can reduce the risk of hip and other non-vertebral fractures in osteoporotic elderly patients with Parkinson ’s disease by slowing the loss of bone mineral densities", "OBJECTIVES Estrogen deficiency is the most common cause of postmenopausal osteoporosis and estrogen replacement is well known to retard postmenopausal bone loss . Calcium supplement alone is generally considered to be insufficient for the prevention of bone loss associated with estrogen deficiency while the role of calcitriol is unclear . In the present study we examined the efficacy different doses of estrogen or calcitriol in the prevention of postmenopausal bone loss in Thais . METHODS The subjects consisted of 146 Thai women no more than 6 years postmenopausal . The subjects were r and omly allocated to receive 750 mg supplemental calcium alone , calcium and conjugated equine estrogen ( CEE ) at 0.3 or 0.625 mg , calcium and calcitriol at 0.25 or 0.5 microg daily . Those receiving CEE also took 5 mg medrogestone for 12 days each month . BMD at L2 - 4 and femoral neck were measured at baseline 1 year and 2 years after treatments . Data were expressed as mean + /- S.E. RESULTS Subjects on supplemental calcium alone had approximately 2.5 % decreases in L2 - 4 ( P femoral BMD ( P vertebral BMD ( P BMD was demonstrated at the femoral neck . Likewise , 0.625 mg of CEE induced 5.4 + /- 1.4 % increase in vertebral BMD at 2 years ( P femoral BMD . In regard to calcitriol , no significant change in vertebral or femoral BMD was demonstrated with either 0.25 or 0.5 microg calcitriol . CONCLUSION We concluded that calcitriol is effective in the prevention of early postmenopausal bone loss in Thais . It represents an option for the prevention of osteoporosis in postmenopausal women who are contraindicated for estrogen replacement", "An unexplained loss of muscle strength occurs with aging . Vitamin D deficiency can cause myopathy and administration of 1,25-dihydroxyvitamin D3 [ 1,25-(OH2)D3 ] to persons with low serum concentrations can improve strength . To test the hypothesis that the weakness associated with aging is in part due to inadequate serum concentrations of [ 1,25-(OH2)D3 ] , we conducted a r and omized , controlled , double blinded trial in 98 men and women volunteers over 69 yr old . Treatment consisted of 0.25 micrograms 1,25-(OH)2D3 , orally , twice per day or identical placebo for 6 months . Leg muscle strength of the quadriceps was measured with an isokinetic dynamometer . There was no difference between the two groups at 1 week , 1 month , or 6 months of treatment in any of the measures of muscle strength . We conclude that oral administration of 0.5 micrograms 1,25-(OH)2D3/day does not improve muscle strength in older persons . Further research is needed to determine the etiology of the decline in muscle strength associated with aging", "Background —Low 25-hydroxyvitamin D levels , commonly found in older patients with heart failure , may contribute to the chronic inflammation and skeletal myopathy that lead to poor exercise tolerance . We tested whether vitamin D supplementation of patients with heart failure and vitamin D insufficiency can improve physical function and quality of life . Methods and Results —In a r and omized , parallel group , double-blind , placebo-controlled trial , patients with systolic heart failure aged ≥70 years with 25-hydroxyvitamin D levels received 100000 U of oral vitamin D2 or placebo at baseline and 10 weeks . Outcomes measured at baseline , 10 weeks , and 20 weeks were 6-minute walk distance , quality of life ( Minnesota score ) , daily activity measured by accelerometry , Functional Limitations Profile , B-type natriuretic peptide , and tumor necrosis factor-&agr;. Participants in the vitamin D group had an increase in their 25-hydroxyvitamin D levels compared with placebo at 10 weeks ( 22.9 versus 2.3 nmol/L [ 9.2 versus 0.9 ng/mL ] ; P The 6-minute walk did not improve in the treatment group relative to placebo . No significant benefit was seen on timed up and go testing , subjective measures of function , daily activity , or tumor necrosis factor . Quality of life worsened by a small , but significant amount in the treatment group relative to placebo . B-type natriuretic peptide decreased in the treatment group relative to placebo ( −22 versus + 78 pg/mL at 10 weeks ; P=0.04 ) . Conclusions —Vitamin D supplementation did not improve functional capacity or quality of life in older patients with heart failure with vitamin D insufficiency . Clinical Trial Registration —www.controlled-trials.com . Identifier : IS RCT N51372896", "OBJECTIVE to determine the effect of risk factor modification and balance exercise on falls rates in residential care homes . DESIGN cluster r and omised controlled trial . PARTICIPANTS 196 residents ( aged 60 years or over ) in 20 residential care homes were enrolled ( 38 % response rate ) . Homes were r and omly allocated to intervention and control arms . A total of 102 residents were consigned to the intervention arm and 94 to the control arm . INTERVENTION a multifactorial falls prevention programme including 3 months gait and balance training , medication review , podiatry and optometry . MAIN OUTCOME MEASURES number of falls/recurrent falls per person , number of medications per person , and change in Tinetti gait and balance measure . RESULTS in the intervention group there was a mean of 2.2 falls per resident per year compared with 4.0 in the control group ; this failed to reach statistical significance ( P = 0.2 ) once the intra-cluster correlation ( ICC , 0.10 ) had been accounted for . Several risk factors were reduced in the intervention arm . CONCLUSIONS falls risk factor reduction is possible in residents of care homes . A modest reduction in falls rates was demonstrated but this failed to reach statistical significance", "BACKGROUND Different dosing protocol s have been used for vitamin D supplementation , but there has been a lack of comparative data among them . OBJECTIVE Our objective was to determine whether the same cumulative dose of vitamin D3 produces different effects if it is given daily , weekly , or monthly . DESIGN Women , age 81 + /- 8 yr ( + /- sd , n = 48 ) , who had undergone surgery to repair hip fracture were r and omized to vitamin D3-supplementation protocol s at 1,500 IU daily , or 10,500 IU once weekly , or 45,000 IU once every 28 d. The primary outcome measure was the serum 25-hydroxyvitamin D [ 25(OH)D ] concentration attained . RESULTS Initially , serum 25(OH)D concentrations for daily , weekly , and monthly groups were , respectively , 15.13 + /- 6.9 , 15.7 + /- 10.1 , and 16.2 + /- 10.1 ng/ml . By d 7 , these had increased significantly in all the groups ( P serum 25(OH)D and serum 1,25-dihydroxyvitamin D had increased significantly ( P serum 25(OH)D with daily , weekly , and monthly dosing were , respectively , 33.2 + /- 8.5 , 29.2 + /- 8.9 , and 37.1 + /- 10.3 ng/ml ; there were no significant differences among these values . CONCLUSIONS Supplementation with vitamin D can be achieved equally well with daily , weekly , or monthly dosing frequencies . Therefore , the choice of dose frequency can be based on whichever approach will optimize an individual 's adherence with long-term vitamin D supplementation", "Estrogen deficiency and declining calcium absorption due to reduced calcitriol levels or intestinal resistance to calcitriol , are important factors in the pathogenesis of age-related bone loss . The main objective of this study was to examine the effect of estrogen and 1,25-dihydroxyvitamin D therapy given individually or in combination on bone loss in elderly women . Four hundred eighty-nine elderly women with normal bone density for their age , aged 65 - 77 yr , were entered into a r and omized double blind , placebo-controlled trial . Women were r and omized to one of four groups : conjugated estrogens ( 0.625 mg , daily ) to women without a uterus ( estrogen replacement therapy ) plus medroxyprogesterone acetate ( 2.5 mg , daily ) to women with a uterus ( hormone replacement therapy ) , calcitriol ( 0.25 microg twice daily ) , a combination of hormone replacement therapy/estrogen replacement therapy plus calcitriol , or placebos for 3 yr . The primary outcome was the change in bone mineral density of the femoral neck and spine . In the intent to treat analysis , hormone therapy ( hormone replacement therapy/estrogen replacement therapy ) produced a mean ( + /-1 SD ) increase in bone mineral density of 2.98 % ( + /-5.45 % ) at the femoral neck ( P total hip and trochanter bone mineral density . Calcitriol increased bone mineral density 0.10 % ( + /- 4.27 % ) at the femoral neck ( P = 0.57 ) and 1.65 % ( + /- 4.83 % ) at the spine ( P of hormone replacement therapy/estrogen replacement therapy + calcitriol increased bone mineral density 3.80 % ( + /-4.95 % ) at the femoral neck ( P hip and trochanter . All three treatment groups differed significantly from placebo at the spine and for the hormone replacement therapy/estrogen replacement therapy groups at the femoral neck , spine , total hip and trochanter . There were no significant differences between combination therapy and hormone replacement therapy/estrogen replacement therapy alone on bone mineral density at any site in the intent to treat analysis . In a secondary analysis of the effect in women who were adherent to treatment , calcitriol had a more significant effect on spine ( P = 0.003 ) and total hip ( P = 0.004 ) . The increase in bone mineral density in the adherent groups of women was always higher compared with the intent to treat groups . Combination therapy compared with hormone replacement therapy/estrogen replacement therapy alone produced a significantly greater response in trochanter ( P = 0.007 ) and total hip bone mineral density ( P = 0.0017 ) . In summary , hormone replacement therapy/estrogen replacement therapy alone and in combination with calcitriol therapy was highly effective in reducing bone resorption and increasing bone mineral density at the hip and other clinical ly relevant sites in a group of elderly women , with normal bone density for their age . Calcitriol was effective in increasing spine bone mineral density . In the adherent women , combination therapy with hormone replacement therapy/estrogen replacement therapy and calcitriol increased bone mineral density significantly more in the total hip and trochanter than did hormone replacement therapy/estrogen replacement therapy alone", "CONTEXT Observational studies show an association between low vitamin D status assessed by circulating 25-hydroxyvitamin D and cardiovascular events and mortality . Data from r and omized controlled trials are limited . OBJECTIVE The aim of this study was to test whether daily doses of vitamin D(3 ) at 400 or 1000 IU/d for 1 yr affected conventional markers of cardiovascular disease ( CVD ) risk . DESIGN We conducted a parallel-group , double-blind , placebo-controlled r and omized controlled trial . R and omization was computer generated . Participants and study investigators were blinded to intervention groupings throughout the trial . SETTING The study was conducted at the Clinical Research Facility , University of Aberdeen , United Kingdom . PARTICIPANTS A total of 305 healthy postmenopausal women aged 60 - 70 yr were recruited for the study . INTERVENTION Each woman received a daily capsule of 400 or 1000 IU vitamin D(3 ) or placebo r and omly allocated . MAIN OUTCOME MEASURES Primary outcomes were serum lipid profile [ total , high-density lipoprotein , and low-density lipoprotein cholesterol ; triglycerides ; and apolipoproteins A-1 and B100 ] , insulin resistance ( homeostatic model assessment ) , inflammatory biomarkers ( high-sensitivity C-reactive protein , IL-6 , soluble intracellular adhesion molecule-1 ) , and blood pressure . RESULTS A total of 265 ( 87 % ) participants completed all study visits . Small differences between groups for serum apolipoprotein B100 change [ repeated measures ANOVA , P=0.04 ; mean ( sd ) , -1.0 ( 10.0 ) mg/dl ( 400 IU ) ; -1.0 ( 10.0 ) mg/dl ( 1000 IU ) ; and + 0.02 ( 10.0 ) mg/dl ( placebo ) ] were not considered clinical ly significant . Other systemic markers for CVD risk remained unchanged . There was significant seasonal variation in systolic and diastolic blood pressure independent of vitamin D dose ( P ( sd ) reduction in systolic blood pressure from winter to summer was -6.6 ( 10.8 ) mm Hg . CONCLUSIONS Improving vitamin D status through dietary supplementation is unlikely to reduce CVD risk factors . Confounding of seasonality should be recognized and addressed in future studies of vitamin", "The necessity and safety of an oral calcium ( Ca ) and vitamin D regimen was evaluated in a population of 66 independently living and 73 institutionalized elderly women over an 11-week winter period . The members of both groups were r and omly assigned into trial and control groups . Serum Ca , creatinine , and calcidiol levels were measured before and after the trial . The regimen consisted of 1.558 g of Ca and 45 micrograms ( equal to 1,800 IU ) of vitamin D administered daily in addition to the normal diet . The controls received no treatment . A majority of the elderly subjects living independently had ensured their Ca , and a quarter of them also their vitamin D intake on their own initiative . The mean serum calcidiol concentration before the trial was 24.1 nmol/L in the institutionalized and 38.5 nmol/L in the elderly subjects living independently ( P less than .001 ) . After the trial , serum calcidiol was 10.4 nmol/L in the institutionalized control subjects and had decreased ( P less than .001 ) in both control groups , but increased ( P less than .001 ) in both treatment groups . The safety indicators , serum Ca , creatinine , and calcidiol , did not indicate any group or individual side effect", "To evaluate the effects of alfacalcidol on bone turnover in elderly women with osteoporosis , an open-label , prospect i ve , calcium-controlled study was conducted . A total of 80 patients with osteoporosis were divided into two groups : the control group , group C ( mean age , 78.0 years ) , in which patients were given calcium , and group D ( mean age , 77.4 years ) , in which the patients were given alfacalcidol 1 µg/day together with calcium for 6 months . Calcium regulation , lumbar bone mineral density ( LBMD ) , and markers for bone turnover were assessed . A significant increase in urinary calcium/creatinine ratio ( 90 % increase from baseline at 3 months ; P = 0.0083 , and 60 % at 6 months ; P = 0.0091 ) and a significant decrease in serum parathyroid hormone ( 30 % decrease from baseline at 6 months ; P of bone resorption markers ( deoxypyridinoline and N-telopeptide ) at 6 months ( about 15 % decrease from the baseline values ) were observed in group D compared with the corresponding changes in group C. The changes in bone formation markers ( bone-derived alkaline phosphatase and osteocalcin ) in group D were significantly different at 6 months ( −21.5 % ; P = 0.0047 and −13.4 % ; P = 0.0032 , respectively ) from the values in group C. The magnitudes of the decrease in bone turnover markers were highly correlated with the corresponding baseline values , suggesting that alfacalcidol treatment effectively reduces bone turnover in patients with high bone turnover rates . The LBMD in group D increased by 1.7 % and that in group C decreased by 1.6 % ( P = 0.0384 ) . The changes in calcium metabolism and LBMD were in good agreement with those in previous reports . Although the changes in bone turnover markers in group D were slight , significant reduction in bone turnover with alfacalcidol treatment , together with the change in calcium metabolism , may account for the effects of alfacalcidol on BMD and on fracture prevention reported previously . In conclusion , alfacalcidol reduces bone turnover in elderly women with high-bone-turnover osteoporosis , and it may have beneficial effects on bone", "A significant reduction in bone mineral density occurs in stroke patients on the hemiplegic side , correlating with the degree of paralysis and vitamin D deficiency due to malnutrition , sunlight deprivation , and immobilization-induced hypercalcemia , and increases the risk of hip fracture . We evaluated the effect of ipriflavone and 1alpha-hydroxyvitamin D3 [ 1alpha(OH)D3 ; vitamin D3 ] administration on bone mineral density preservation as compared with untreated controls . In a r and omized and prospect i ve study of 103 patients with hemiplegia after stroke ( the mean duration of illness was 4.8 yr ) , 68 ( 34 patients in each group ) were given 600 mg ipriflavone or 1 microg vitamin D3 daily for 12 mo , whereas the remaining 35 patients received no drug . Bone mineral density on the hemiplegic side decreased by 1.4 % in the ipriflavone group , 3.8 % in the vitamin D3 group , and 5.4 % in the control group ( P 25-hydroxyvitamin D insufficiency , increased serum ionized calcium , and low levels of 1 , 25-dihydroxyvitamin D , suggesting immobilization-induced hypercalcemia and inhibition of renal synthesis of 1 , 25-dihydroxyvitamin D. After treatment , the serum 1 , 25-dihydroxyvitamin D level increased by 139.9 % in the ipriflavone group and by 26.9 % in the vitamin D3 group . Significant decreases in the serum ionized calcium and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen , and increases in parathyroid hormone and bone Gla protein were observed in the ipriflavone group , whereas no changes occurred in the other two groups . One patient in the untreated group suffered a hip fracture , compared with none in the ipriflavone and vitamin D3 groups . These results suggest that ipriflavone is more efficacious than vitamin D3 in the prevention of decreased bone mineral density in hemiplegic stroke patients because it decreases serum calcium levels through inhibition of bone resorption and cause a subsequent increase in 1 , 25-dihydroxyvitamin D concentration", "Background It is undetermined whether calcium supplementation has an effect on obesity or body composition in postmenopausal women . The purpose of the study is to detect the effect of calcium supplementation on indices of obesity and body composition . Methods This is a secondary analysis of data from a population -based , double-blind , placebo-controlled , r and omized trial design ed to determine the effects of calcium and vitamin D on osteoporotic fractures . The cohort included 1179 postmenopausal women who were r and omly assigned into one of three groups : 1 ) supplemental calcium ( 1400 mg/d or 1500 mg/d ) plus vitamin D placebo ( Ca-only group ) ; 2 ) supplemental calcium ( 1400 mg/d or 1500 mg/d ) plus supplemental vitamin D3 ( 1100 IU/d ) ( Ca + D group ) ; or , 3 ) two placebos ( placebo group ) . After applying the exclusion criteria for this analysis , 870 subjects were included in this study . The primary outcomes for the present study were changes in body mass index , trunk fat , trunk lean , and percentage of trunk fat after calcium supplementation . Results Changes in trunk fat , trunk lean , and percentage of trunk fat were significantly different between the calcium intervention groups ( Ca-only group or Ca + D group ) and the placebo group during the trial ( P calcium intervention groups gained less trunk fat and maintained more trunk lean when compared to the placebo group . No significant difference was observed for body mass index between groups . Conclusion Calcium supplementation over four years has a beneficial effect on body composition in postmenopausal women", "BACKGROUND The Food and Nutrition Board of the National Academy of Sciences states that 95 microg vitamin D/d is the lowest observed adverse effect level ( LOAEL ) . OBJECTIVE Our objective was to assess the efficacy and safety of prolonged vitamin D3 intakes of 25 and 100 microg ( 1000 and 4000 IU)/d . Efficacy was based on the lowest serum 25-hydroxyvitamin D [ 25(OH)D ] concentration achieved by subjects taking vitamin D3 ; potential toxicity was monitored by measuring serum calcium concentrations and by calculating urinary calcium-creatinine ratios . DESIGN Healthy men and women ( n = 61 ) aged 41 + /- 9 y ( mean + /- SD ) were r and omly assigned to receive either 25 or 100 microg vitamin D3/d for 2 - 5 mo , starting between January and February . Serum 25(OH)D was measured by radioimmunoassay . RESULTS Baseline serum 25(OH)D was 40.7 + /- 15.4 nmol/L ( mean + /- SD ) . From 3 mo on , serum 25(OH)D plateaued at 68.7 + /- 16.9 nmol/L in the 25-microg/d group and at 96.4 + /- 14.6 nmol/L in the 100-microg/d group . Summertime serum 25(OH)D concentrations in 25 comparable subjects not taking vitamin D3 were 46.7 + /- 17.8 nmol/L. The minimum and maximum plateau serum 25(OH)D concentrations in subjects taking 25 and 100 microg vitamin D3/d were 40 and 100 nmol/L and 69 and 125 nmol/L , respectively . Serum calcium and urinary calcium excretion did not change significantly at either dosage during the study . CONCLUSIONS The 100-microg/d dosage of vitamin D3 effectively increased 25(OH)D to high-normal concentrations in practically all adults and serum 25(OH)D remained within the physiologic range ; therefore , we consider 100 microg vitamin D3/d to be a safe intake", "BACKGROUND Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers . However , interventional studies to test this effect are lacking . OBJECTIVE The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk of all types . DESIGN This was a 4-y , population -based , double-blind , r and omized placebo-controlled trial . The primary outcome was fracture incidence , and the principal secondary outcome was cancer incidence . The subjects were 1179 community-dwelling women r and omly selected from the population of healthy postmenopausal women aged > 55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were r and omly assigned to receive 1400 - 1500 mg supplemental calcium/d alone ( Ca-only ) , supplemental calcium plus 1100 IU vitamin D3/d ( Ca + D ) , or placebo . RESULTS When analyzed by intention to treat , cancer incidence was lower in the Ca + D women than in the placebo control subjects ( P unadjusted relative risks ( RR ) of incident cancer in the Ca + D and Ca-only groups were 0.402 ( P = 0.01 ) and 0.532 ( P = 0.06 ) , respectively . When analysis was confined to cancers diagnosed after the first 12 mo , RR for the Ca + D group fell to 0.232 ( CI : 0.09 , 0.60 ; P treatment and serum 25-hydroxyvitamin D concentrations were significant , independent predictors of cancer risk . CONCLUSIONS Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women . This trial was registered at clinical trials.gov as NCT00352170", "BACKGROUND Increased vitamin D intake may preserve or increase bone mineral density ( BMD ) in older persons . OBJECTIVE A 2-y double-blind study was undertaken to determine whether weekly administration of 10 000 units of vitamin D(2 ) maintained or increased BMD in younger postmenopausal women more efficiently than did calcium supplements alone . DESIGN One hundred eighty-seven women who were > or= 1 y postmenopausal were r and omly assigned to take either 1000 mg Ca/d after the evening meal or 1000 mg Ca/d plus 10 000 U vitamin D(2)/wk in a double-blind , placebo-controlled format . The BMD of the proximal forearm , lumbar spine , femoral neck , Ward 's triangle , and femoral trochanter was measured at 6-mo intervals by osteodensitometry . RESULTS During the 2-y period , there was no significant difference in the change in BMD at any site between the subjects taking calcium supplements and those taking calcium plus vitamin D(2 ) . Both groups significantly ( P gained BMD in Ward 's triangle and the femoral trochanter but significantly ( P lost bone in the proximal radius . There was no significant change in the lumbar spine or femoral neck BMD . CONCLUSION In younger postmenopausal women ( age : 56 y ) whose average baseline serum 25-hydroxyvitamin D concentration was well within the normal range , the addition of 10 000 U vitamin D(2)/wk to calcium supplementation at 1000 mg/d did not confer benefits on BMD beyond those achieved with calcium supplementation alone", "BACKGROUND Supplementation with calcium and vitamin D reduces bone loss and prevents fractures in elderly people , but it is not known whether any lasting benefit remains if the supplements are discontinued . OBJECTIVE The objective was to determine whether gains in bone mineral density ( BMD ) induced by calcium and vitamin D supplementation persist after supplement withdrawal . DESIGN Two-hundred ninety-five healthy , elderly men and women ( aged > /=68 y ) who had completed a 3-y r and omized , placebo-controlled trial of calcium and vitamin D supplementation were followed for an additional 2 y during which no study supplements were given . BMD was measured by dual-energy X-ray absorptiometry , and biochemical variables related to calcium metabolism and bone turnover were measured . RESULTS In the 128 men , supplement-induced increases in spinal and femoral neck BMD were lost within 2 y of supplement discontinuation , but small benefits in total-body BMD remained . In the 167 women , there were no lasting benefits in total-body BMD or at any bone site . Consistent with the observations on BMD , the bone turnover rates in both men and women ( as measured by serum osteocalcin concentrations ) returned to their original higher concentrations within the same 2-y period . CONCLUSION Discontinued calcium and vitamin D supplementation has limited cumulative effect on bone mass in men and women aged > /=68", "BACKGROUND There is currently no consensus on the effect of dietary protein intake on the skeleton , but there is some indication that low calcium intakes adversely influence the effect of dietary protein on fracture risk . OBJECTIVE The objective of the present study was to determine whether supplemental calcium citrate malate and vitamin D influence any associations between protein intake and change in bone mineral density ( BMD ) . DESIGN Associations between protein intake and change in BMD were examined in 342 healthy men and women ( aged > or = 65 y ) who had completed a 3-y , r and omized , placebo-controlled trial of calcium and vitamin D supplementation . Protein intake was assessed at the midpoint of the study with the use of a food-frequency question naire and BMD was assessed every 6 mo by dual-energy X-ray absorptiometry . RESULTS The mean ( + /-SD ) protein intake of all subjects was 79.1 + /- 25.6 g/d and the mean total calcium intakes of the supplemented and placebo groups were 1346 + /- 358 and 871 + /- 413 mg/d , respectively . Higher protein intake was significantly associated with a favorable 3-y change in total-body BMD in the supplemented group ( in a model containing terms for age , sex , weight , total energy intake , and dietary calcium intake ) but not in the placebo group . The pattern of change in femoral neck BMD with increasing protein intake in the supplemented group was similar to that for the total body . CONCLUSION Increasing protein intake may have a favorable effect on change in BMD in elderly subjects supplemented with calcium citrate malate and vitamin", "BACKGROUND Adequate intakes of calcium and vitamin D reduce bone loss and fracture risk in the elderly . Other nutrients also affect bone health , and adequate intakes may influence bone turnover and balance . OBJECTIVE We compared the long-term effects on bone turnover markers and calciotropic hormones of a multinutrient supplement , a calcium and vitamin D supplement , and dietary instruction aim ed at increasing calcium intake through foods . DESIGN Ninety-nine healthy postmenopausal women participated in a 3-y , r and omized trial , receiving either 1 ) supplemental calcium ( 1450 mg/d ) and vitamin D [ 10 microg ( 400 IU)/d ] , 2 ) calcium , vitamin D , and other nutrients ( multinutrient supplement ) , or 3 ) dietary instruction ( dietary control group ) . Data are from 83 subjects who completed the trial . RESULTS Increases over baseline in calcium intakes and serum 25-hydroxyvitamin D concentrations were sustained over 3 y in all treatment groups . Circulating parathyroid hormone concentrations were reduced at year 1 in all treatment groups but trended toward baseline thereafter . Bone turnover markers followed a similar pattern , and none of the changes in biochemical concentrations differed significantly between groups . CONCLUSIONS All 3 interventions offer long-term feasibility for increasing calcium intake and serum 25-hydroxyvitamin D concentrations . The dietary addition of micronutrients implicated in skeletal physiology confers no obvious bone-sparing effect in healthy postmenopausal women beyond that of calcium and vitamin D alone . The attenuation over time in suppression of parathyroid hormone and bone turnover might help explain why nutrient intervention tends to have less of a bone-sparing effect than do skeletally active medications such as estrogen or bisphosphonates", "A r and omized double-blind controlled trial of a single oral dose of 2.5 mg ( 100,000 IU ) cholecalciferol ( vitamin D3 ) was conducted in the winter in 189 healthy free-living men and women aged 63 - 76 y. The mean baseline serum concentration for 25-hydroxyvitamin D was 34.5 nmol/L and for parathyroid hormone 3.18 pmol/L. After 5 wk , mean serum 25-hydroxyvitamin D concentrations were 60 % higher in the treated than in the placebo group ( P parathyroid hormone concentrations in the treated compared with the placebo group ( P serum calcium were seen . Findings suggest that 25-hydroxyvitamin D has a physiological role in the regulation of parathyroid secretion independent of serum calcium in healthy elderly people . Parathyroid concentrations rise and 25-hydroxyvitamin D concentrations decline with age . These results may have implication s for the prevention of osteoporotic fractures that occur with increased frequency in winter and in elderly people", "Introduction Osteoporotic fractures in older people are a major and increasing public health problem . We examined the effect of vitamin D supplementation on fracture rate in people living in sheltered accommodation . Methods In a pragmatic double blind r and omised controlled trial of 3 years duration , we examined 3,440 people ( 2,624 women and 816 men ) living in residential or care home . We used four-monthly oral supplementation using 100,000 IU vitamin D2 ( ergocalciferol ) . As a main outcome measure , we used the incidence of first fracture using an intention to treat analysis . This was a multicentre study in 314 care homes or sheltered accommodation complexes in South Wales , UK . Results The vitamin D and placebo groups had similar baseline characteristics . In intention-to-treat analysis , 205 first fractures occurred in the intervention group during a total of 2,846 person years of follow-up ( 7 fractures per 100 people per year of follow-up ) , with 218 first fractures in the control group over 2,860 person years of follow-up . The hazard ratio of 0.95 ( 95 % confidence interval 0.79–1.15 ) for intervention compared to control was not statistically significant . ConclusionS upplementation with four-monthly 100,000 IU of oral vitamin D2 is not sufficient to affect fracture incidence among older people living in institutional care", "Abstract : Supplementation of elderly institutionalized women with vitamin D and calcium decreased hip fractures and increased hip bone mineral density . Quantitative ultrasound ( QUS ) measurements can be performed in nursing homes , and easily repeated for follow-up . However , the effect of the correction of vitamin D deficiency on QUS parameters is not known . Therefore , 248 institutionalized women aged 62–98 years were included in a 2-year open controlled study . They were r and omized into a treated group ( n = 124 ) , receiving 440 IU of vitamin D3 combined with 500 mg calcium ( 1250 mg calcium carbonate , Novartis ) twice daily , and a control group ( n = 124 ) . One hundred and three women ( 42 % ) , aged 84.5 ± 7.5 years , completed the study : 50 in the treated group , 53 in the controls . QUS of the calcaneus , which measures BUA ( broadb and ultrasound attenuation ) and SOS ( speed of sound ) , and biochemical analysis were performed before and after 1 and 2 years of treatment . Only the results of the women with a complete follow-up were taken into account . Both groups had low initial mean serum 25-hydroxyvitamin D levels ( 11.9 ± 1.2 and 11.7 ± 1.2 mg/l ; normal range 6.4–40.2 mg/l ) and normal mean serum parathyroid hormone ( PTH ) levels ( 43.1 ± 3.2 and 44.6 ± 3.5 ng/l ; normal range 10–70 ng/l , normal mean 31.8 ± 2.3 ng/l ) . The treatment led to a correction of the metabolic disturbances , with an increase in 25-hydroxyvitamin D by 123 % ( p50.01 ) and a decrease in PTH by 18 % ( p50.05 ) and of alkaline phosphatase by 15 % ( p50.01 ) . In the controls there was a worsening of the hypovitaminosis D , with a decrease of 25-hydroxyvitamin D by 51 % ( p50.01 ) and an increase in PTH by 51 % ( p50.01 ) , while the serum calcium level decreased by only 2 % ( p5 0.01 ) . After 2 years of treatment BUA increased significantly by 1.6 % in the treated group ( p50.05 ) , and decreased by 2.3 % in the controls ( p50.01 ) . Therefore , the difference in BUA between the treated subjects and the controls ( 3.9 % ) was significant after 2 years ( p50.01 ) . However , SOS decreased by the same amount in both groups ( approximately 0.5 % ) . In conclusion , BUA , but not SOS , reflected the positive effect on bone of supplementation with calcium and vitamin D3 in a population of elderly institutionalized women", "BACKGROUND Epidemiological evidence supports a relationship between vitamin D and mental well-being , although evidence from large-scale placebo-controlled intervention trials is lacking . AIMS To examine if vitamin D supplementation has a beneficial effect on mood in community-dwelling older women ; if a single annual large dose of vitamin D has a role in the prevention of depressive symptoms ; and if there is an association between serum 25-hydroxyvitamin D levels and mental health . METHOD A double-blind , r and omised , placebo-controlled trial of women aged 70 or older ( the Vital D Study : IS RCT N83409867 and ACTR12605000658617 ) . Participants were r and omly assigned to receive 500 000 IU vitamin D(3 ) ( cholecalciferol ) orally or placebo every autumn/winter for 3 - 5 consecutive years . The tools utilised at various time points were the General Health Question naire , the 12-item Short Form Health Survey , the Patient Global Impression-Improvement scale and the WHO Well-Being Index . Serum 25-hydroxyvitamin D levels were measured in a subset of 102 participants . RESULTS In this non- clinical population , no significant differences between the vitamin D and placebo groups were detected in any of the measured outcomes of mental health . Serum 25-hydroxyvitamin D levels in the vitamin D group were 41 % higher than the placebo group 12 months following their annual dose . Despite this difference , scores from the question naires did not differ . Furthermore , there was no interaction between those on antidepressant/anxiety medication at baseline and the treatment groups . CONCLUSIONS The lack of improvement in indices of mental well-being in the vitamin D group does not support the hypothesis that an annual high dose of vitamin D(3 ) is a practical intervention to prevent depressive symptoms in older community-dwelling women", "The purpose of this study was to ( 1 ) quantify the healing process of the human osteoporotic proximal humerus fracture ( PHF ) expressed in terms of callus formation over the fracture region using BMD scanning , and ( 2 ) quantify the impact of medical intervention with vitamin D3 and calcium on the healing process of the human osteoporotic fracture . The conservatively treated PHF was chosen in order to follow the genuine fracture healing without influence of osteosynthetic material s or casts . Thirty women ( mean age = 78 years ; range = 58–88 ) with a PHF , osteoporosis or osteopenia ( based on a hip scan , WHO criteria ) , and not taking any drugs related to bone formation , including calcium or vitamin D supplementation , were r and omly assigned to either oral 800 IU vitamin D3 plus 1 g calcium or placebo , in a double-blind prospect i ve study . We measured biochemical , radiographic , and bone mineral density effect parameters to evaluate the impact on the healing process . Scanning procedures of the fractured shoulder included use of a fixation device to obtain the highest possible precision . Double scans of the fractured shoulder revealed a coefficient of variation ( CV ) on BMD measurements that improved from 2.8 % immediately after fracture occurrence to 1.7 % at 12 weeks ( P = 0.003 ) approaching the 1.2 % levels observed over the healthy shoulder . BMD was similar in the two groups at baseline ( active 0.534 g/cm2 vs. placebo 0.518 g/cm2 ) , and both increased over the 12-week observation period , with peak levels in week 6 . By week 6 BMD levels were higher in the active group ( 0.623 g/cm2 ) compared with the placebo group ( 0.570 g/cm2 , P = 0.006 ) . Thirty seven percent of the patients presented with vitamin D levels below 30 nmol/l , indicative of mild vitamin D insufficiency . In conclusion , we have demonstrated that it is possible to quantify callus formation of the PHF with sufficiently high precision to demonstrate the positive influence of vitamin D3 and calcium over the first 6 weeks after fracture . Whether this results in more stable fractures , extends to other fracture types , or applies to other osteogenic bone agents such as bisphosphonates remains to be examined", "An ongoing r and omized clinical trial of 3 years duration is being undertaken to evaluate the recurrent fracture rate and safety profile associated with low-dose calcitriol versus calcium supplementation in women with at least 3 years postmenopausal osteoporosis who are under the age of 80 years . A total of 856 patients were su bmi tted for possible inclusion in the study by 123 primary care physicians , and 636 met all entry requirements . Each patient was r and omly allocated to receive either 0.25 micrograms of calcitriol twice daily or calcium supplementation of 1,000 mg/d . If significant hypercalcemia developed ( greater than 2.6 mmol/L ) or a deterioration in renal function was observed , the dose of trial medication was to be halved or stopped if laboratory values did not return to normal . Patients were given no specific instructions regarding dietary calcium intake . To date , 528 patient-years experience with calcitriol and 527 patient-years experience with calcium the calcium supplementation have been accumulated . Thus far , low-dose calcitriol has not been observed to cause hypercalcemia , deterioration in renal function , or nephrocalcinosis . At 1 year , a loss in total anterior height ( P less than .05 ) has been detected in the calcium-treated group compared with the calcitriol-treated group . Thus , calcitriol appears to preserve spinal height . Long-term follow-up of all patients for 2 or 3 years will be continued", "We previously observed that a creatinine clearance ( CrCl ) of number of fallers and falls in a community-dwelling elderly population and postulated that this increased risk is due to the associated significant lower D-hormone serum levels . To test our hypothesis , we investigated in a post hoc analysis of a double-blind r and omized study whether treatment with alfacalcidol , a synthetic prodrug of the D-hormone , can reduce the high incidence of fallers and the high risk of falls associated with low CrCl . Of 378 Swiss community-dwelling women ( n=191 ) and men ( n=187 ) , aged 70 years and older , 191 received r and omly 1 μg capsules of alfacalcidol ( AlphaD3 : Teva ) , and 187 received one capsule of placebo daily . With the help of question naires we regularly assessed the incidence and frequency of falls . The risk of becoming a faller and the risk of falling were assessed in multivariate-controlled logistic regression models according to treatment groups and according to a CrCl cut-off of 65 ml/min . The presented results are from ITT analyses . In participants with a CrCl of with alfacalcidol was , compared with placebo , associated with a significant reduction in the number of fallers ( 14/72 versus 25/70 ; OR 0.26 , 95 % CI 0.08–0.80 , P=0.019 ) , and a significant reduction of the number of falls ( 16/72 versus 28/70 ; OR 0.29 , 95 % CI 0.09–0.88 , P=0.028 ) . No such association was observed in participants with a CrCl of ≥65 ml/min ( for fallers 26/120 versus 21/116 ; OR 0.92 95 % CI 0.34–2.52 , P=0.875 ; for falls 32/120 versus 23/116 ; OR 0.93 95 % CI 0.34–2.54 , P=0.885 ) . In the placebo group frequency of falls was dependent on CrCl ( P=0.006 ) , whereas in the alfacalcidol treatment group frequency of falls was independent of CrCl ( P=0.494 ) . No cases of clinical ly relevant hypercalcemia were observed . In a community-dwelling population of elderly men and women with a CrCl of , treatment with alfacalcidol can significantly and safely reduce the low CrCl associated increased number of fallers and the high risk of falls", "The Women 's Health Initiative ( WHI ) is a large and complex clinical investigation of strategies for the prevention and control of some of the most common causes of morbidity and mortality among postmenopausal women , including cancer , cardiovascular disease , and osteoporotic fractures . The WHI was initiated in 1992 , with a planned completion date of 2007 . Postmenopausal women ranging in age from 50 to 79 are enrolled at one of 40 WHI clinical centers nationwide into either a clinical trial ( CT ) that will include about 64,500 women or an observational study ( OS ) that will include about 100,000 women . The CT is design ed to allow r and omized controlled evaluation of three distinct interventions : a low-fat eating pattern , hypothesized to prevent breast cancer and colorectal cancer and , secondarily , coronary heart disease ; hormone replacement therapy , hypothesized to reduce the risk of coronary heart disease and other cardiovascular diseases and , secondarily , to reduce the risk of hip and other fractures , with increased breast cancer risk as a possible adverse outcome ; and calcium and vitamin D supplementation , hypothesized to prevent hip fractures and , secondarily , other fractures and colorectal cancer . Overall benefit-versus-risk assessment is a central focus in each of the three CT components . Women are screened for participation in one or both of the components -- dietary modification ( DM ) or hormone replacement therapy (HRT)--of the CT , which will r and omize 48,000 and 27,500 women , respectively . Women who prove to be ineligible for , or who are unwilling to enroll in , these CT components are invited to enroll in the OS . At their 1-year anniversary of r and omization , CT women are invited to be further r and omized into the calcium and vitamin D ( CaD ) trial component , which is projected to include 45,000 women . The average follow-up for women in either CT or OS is approximately 9 years . Concerted efforts are made to enroll women of racial and ethnic minority groups , with a target of 20 % of overall enrollment in both the CT and OS . This article gives a brief description of the rationale for the interventions being studied in each of the CT components and for the inclusion of the OS component . Some detail is provided on specific study design choices , including eligibility criteria , recruitment strategy , and sample size , with attention to the partial factorial design of the CT . Some aspects of the CT monitoring approach are also outlined . The scientific and logistic complexity of the WHI implies particular leadership and management challenges . The WHI organization and committee structure employed to respond to these challenges is also briefly described", "UNLABELLED This study of 9605 community-dwelling residents supports that vitamin D and calcium supplementation may prevent osteoporotic fractures in elderly in a northern European region known to be deficient in vitamin D , especially during winter periods . INTRODUCTION We evaluated the effect of two programs for the prevention of osteoporotic fractures leading to acute hospital admission in a population of elderly community-dwelling residents . MATERIAL S AND METHODS This was a factorial , cluster-r and omized , pragmatic , intervention study . We included 9605 community-dwelling residents aged 66 + years . We offered a prevention program of a daily supplement of 1000 mg of elemental calcium as calcium carbonate and 400 IU ( 10 microg ) of vitamin D3 to a total of 4957 participants . Another program with evaluation and suggestions for the improvement of the domestic environment was offered to a total of 5063 participants . Both programs included revision of the resident 's current pharmaceutical treatment . We achieved information on osteoporotic fractures in the study population from the Danish Hospital Registration Data base . We defined osteoporotic fractures as low energy fractures of the proximal humerus , distal forearm , vertebral column , pelvis , cervical femur , and intertrochanteric femur . RESULTS Active participation was 50.3 % in the Calcium and Vitamin D Program and 46.4 % in the Environmental and Health Program . We observed a 16 % reduction in fracture incidence rate ( relative risk [ RR ] , 0.84 ; CI , 0.72 - 0.98 ; p female residents offered the Calcium and Vitamin D Program ( intention-to-prevent analysis ) . CONCLUSIONS This study supports that vitamin D and calcium supplementation may prevent osteoporotic fractures in community-dwelling elderly people in a northern European region known to be deficient in vitamin D , especially during winter periods", "Conflicting data regarding cardiovascular effects of thiazolidinediones ( TZDs ) and extra-skeletal effects of vitamin D supported the need for a definitive trial . The Thiazolidinedione Intervention with vitamin D Evaluation ( TIDE ) trial aim ed to assess the effects of TZDs ( rosiglitazone and pioglitazone ) on cardiovascular outcomes and the effects of vitamin D ( cholecalciferol ) on cancers and mortality . A large multicentre 3 × 2 factorial double-blind placebo-controlled r and omised trial recruited from outpatient primary care and specialty clinics in 33 countries . From June 2009 to July 2010 , 1,332 people with type 2 diabetes and other cardiovascular risk factors aged ≥50 years whose HbA1c was 6.5–9.5 % ( 48–80 mmol/mol ) when using two or fewer glucose-lowering drugs were r and omised by a central computer system to placebo ( n = 541 ) , rosiglitazone 4–8 mg/day ( n = 399 ) or pioglitazone 30–45 mg/day ( n = 392 ) ; 1,221 participants were r and omised to placebo ( n = 614 ) or vitamin D 1,000 IU/day ( n = 607 ) . Participants and all study personnel were blind to treatment allocation . The primary outcome for the TZD arm was the composite of myocardial infa rct ion , stroke or cardiovascular death , and for the vitamin D arm it was cancer or all-cause death . All r and omised participants were included in the primary analysis . From the study design , 16,000 people were to be followed for approximately 5.5 years . However , the trial was stopped prematurely because of regulatory concerns after a mean of 162 days without consideration of the accrued data . In the TZD arm , the cardiovascular outcome occurred in five participants ( 0.9 % ) in the placebo groups and three participants ( 0.4 % ) in the TZD groups ( two allocated to pioglitazone , one to rosiglitazone ) . In the vitamin D arm , the primary outcome occurred in three participants ( 0.5 % ) in the placebo group and in two participants ( 0.3 % ) receiving vitamin D. Adverse events were comparable in all groups . Uncertainty persists regarding the clinical ly relevant risks and benefits of TZDs and vitamin D because of the early cancellation of this comprehensive trial . Clinical Trials.gov NCT00879970 The study was funded by GlaxoSmithKline", "Women with vertebral deformities caused by osteoporosis have more back pain and disability and are at higher risk for subsequent vertebral deformities than women without deformities . Despite the importance of vertebral deformities , there has been a great deal of controversy about how to identify or define them . In order to compare methods for defining vertebral deformities , we studied spinal radiographs from women in the Study of Osteoporotic Fractures ( SOF ) , a cohort study of 9704 non-black women over age 65 recruited from population -based listings in four clinical centers . Using radiographs obtained at the baseline exam , we compared five methods for defining vertebral deformities : one based on a semiquantitative reading by a radiologist and four using vertebral morphometry . The semiquantitative method was compared with the other methods in a r and om sample of 503 films , while the morphometric methods were compared with each other in a larger sample of 9575 films . We tested a system of \" triage \" in which only those films with evidence of deformity were assessed by morphometry . We compared the relationship between deformity , defined by each method , and a variety of clinical criteria including bone mineral density at the lumbar spine , height loss since age 25 , back pain , and incidence of subsequent deformity . Semiquantitative reading and three of the four morphometry-based methods provided similar relationships to clinical criteria . The fourth morphometry method ( based on ratios of each vertebral height to the corresponding height at T4 ) produced significantly weaker relationships for several of the clinical validation criteria . Triage of radiographs rarely result ed in missed deformities and did not reduce the performance of any of the methods . We conclude that use of any of the similar methods , with or without triage , provides a valid approach to defining vertebral deformities", "BACKGROUND Ergocalciferol ( vitamin D(2 ) ) supplementation plays a role in fall prevention , but the effect in patients living in the community in sunny climates remains uncertain . We evaluated the effect of ergocalciferol and calcium citrate supplementation compared with calcium alone on the risk of falls in older women at high risk of falling . METHODS A 1-year population -based , double-blind , r and omized controlled trial of 302 community-dwelling ambulant older women aged 70 to 90 years living in Perth , Australia ( latitude , 32 degrees S ) , with a serum 25-hydroxyvitamin D concentration of less than 24.0 ng/mL and a history of falling in the previous year . Participants were r and omized to receive ergocalciferol , 1000 IU/d , or identical placebo ( hereinafter , ergocalciferol and control groups , respectively ) . Both groups received calcium citrate , 1000 mg/d . Fall data were collected every 6 weeks . RESULTS Ergocalciferol therapy reduced the risk of having at least 1 fall over 1 year after adjustment for baseline height , which was significantly different between the 2 groups ( ergocalciferol group , 53.0 % ; control group , 62.9 % ; odds ratio [ OR ] , 0.61 ; 95 % confidence interval [ CI ] , 0.37 - 0.99 ) . When those who fell were grouped by the season of first fall or the number of falls they had , ergocalciferol treatment reduced the risk of having the first fall in winter and spring ( ergocalciferol group , 25.2 % ; control group , 35.8 % ; OR , 0.55 ; 95 % CI , 0.32 - 0.96 ) but not in summer and autumn , and reduced the risk of having 1 fall ( ergocalciferol group , 21.2 % ; control group , 33.8 % ; OR , 0.50 ; 95 % CI , 0.28 - 0.88 ) but not multiple falls . CONCLUSION Patients with a history of falling and vitamin D insufficiency living in sunny climates benefit from ergocalciferol supplementation in addition to calcium , which is associated with a 19 % reduction in the relative risk of falling , mostly in winter", "OBJECTIVE This study investigated whether a combined regimen of ipriflavone and 1 alpha vitamin D is effective in stopping postmenopausal bone loss . METHODS Ninety-eight postmenopausal women were recruited and r and omly assigned to one of four groups : group 1 , ipriflavone alone ; group 2 , 1 alpha vitamin D alone ; group 3 , combined regimen of ipriflavone and 1 alpha vitamin D ; group 4 , no treatment . Vertebral bone mineral density , measured by dual energy X-ray absorptiometry , serum alkaline phosphatase , calcitonin , parathyroid hormone , osteocalcin , urinary calcium and hydroxyproline were measured before and at the 6th , 12th and 18th month of the study . All comparisons were made using Student 's t-test of means . RESULT There was a significant reduction in vertebral bone loss in the patients receiving the combined therapy ( mean loss after 18 months 0.33 % in the combination group vs. 2.37 % , 1.15 % and 3.70 % in the ipriflavone alone , 1 alpha vitamin D alone , and control groups , respectively ; P postmenopausal bone loss ", "The effects on general and bone metabolism of femoral neck fracture patients of 0.25 μg α-calcoid given orally twice daily ( n=9 ) and 25 μg calcitonin given subcutaneously 30 times ( n=10 ) in 10 weeks were studied against a control ( n = ll ) . Bone histology and histomorphometry showed non-age related osteoporosis in 30 % and osteomalacia in 22 % of the patients studied . Impaired serum vitamin D status was found in 47 – 88 % of patients , secondary hyperparathyroidism and increased serum parathyroid hormone in 59 % and decreased serum calcitonin levels in 69 % . On histology , normal findings and non-age related osteoporosis on histology were associated with low serum levels of 25-hydroxyvitamin D3,1,25- and 24,25-dihydroxy vitamin D3 . Very high serum levels of 1,25-dihydroxyvitamin D3 and low levels of 25-hydroxyvitamin D3 occurred in fracture patients with osteomalacia . Calcitonin improved calcium balance , reduced osteoporosis and increased the serum 1,25- and 24,25-dihydroxyvitamin D3 levels but had no effect on osteomalacia . Vitamin D reduced osteomalacia , slightly increased the serum 1,25-dihydroxyvitamin D3 concentration and decreased serum levels of parathyroid hormone . Both treatments gave a similar slight decrease in serum calcitonin concentrations . A mechanism of action for the treatments is suggested", "The aim was to assess the effects of resistance training and vitamin D supplementation on physical performance of healthy elderly subjects . Ninety-six subjects , aged 70 years or more with 25 OH vitamin D levels of 16 ng/ml or less , were r and omized to a resistance training or control group . Trained and control groups were further r and omized to receive in a double blind fashion , vitamin D 400 IU plus 800 mg of calcium per day or calcium alone . Subjects were followed for nine months . Serum 25 OH vitamin D increased from 12.4+/-2.2 to 25.8+/-6.5 ng/ml among subjects supplemented with vitamin D. Trained subjects had significant improvements in quadriceps muscle strength , the short physical performance test and timed up and go . The latter improved more in trained subjects supplemented with vitamin D. At the end of the follow up , gait speed was higher among subjects supplemented with vitamin ( whether trained or not ) than in non-supplemented subjects ( 838+/-147 and 768+/-127 m/12 min , respectively , p=0.02 ) . Romberg ratio was lower among supplemented controls than non-supplemented trained subjects ( 128+/-40 % and 144+/-37 % , respectively , p=0.05 ) . In conclusion , vitamin D supplementation improved gait speed and body sway , and training improved muscle strength", "OBJECTIVES Assessment of additive impact of alfacalcidol 1 μg daily ( Alfa ) on bone mineral density ( BMD ) and on bone strength in postmenopausal women treated with alendronate 70 mg weekly + 500 mg calcium daily . SUBJECTS AND METHODS In a r and omized , double-blind , placebo controlled study , 279 postmenopausal women with osteoporosis or osteopenia participated ( intention to treat analysis [ ITT ] ; aged 73.6∓4.7 years ) and were treated with 70 mg alendronate ( ALN ) weekly and 500 mg calcium daily for 36 months . In addition , these patients received either 1 μg alfacalcidol ( Alfa ) or placebo ( PLC ) daily . BMD was measured with Dual-Energy-X-ray-Absorptiometry ( DXA ) at the lumbar spine and proximal femur and at forearm and tibia with peripheral quantitative computed tomography ( pQCT ) at regular intervals for 36 months . RESULTS DXA-BMD of lumbar spine ( L1 - 4 ) increased after 36 months , by 6.65 % ( p in trabecular density ( tibia ) ( p=0.002 ) , cortical density ( midshaft tibia ) ( p=0.043 ) , and bone strength ( p=0.001 ) . The remaining parameters showed no differences between the treatment arms , apart cortical bone density at midshaft radius . CONCLUSIONS Alfacalcidol significantly increases the efficacy of alendronate treatment in osteopenic/osteoporotic postmenopausal women on spinal DXA-BMD , cortical and trabecular BMD of the tibia and also bending stiffness of the tibia", "OBJECTIVES To determine the effect of four vitamin D supplement doses on falls risk in elderly nursing home residents . DESIGN Secondary data analysis of a previously conducted r and omized clinical trial . SETTING Seven hundred twenty-five-bed long-term care facility . PARTICIPANTS One hundred twenty-four nursing home residents ( average age 89 ) . INTERVENTION Participants were r and omly assigned to receive one of four vitamin D supplement doses ( 200 IU , 400 IU , 600 IU , or 800 IU ) or placebo daily for 5 months . MEASUREMENTS Number of fallers and number of falls assessed using facility incident tracking data base . RESULTS Over the 5-month study period , the proportion of participants with falls was 44 % in the placebo group ( 11/25 ) , 58 % ( 15/26 ) in the 200 IU group , 60 % ( 15/25 ) in the 400 IU group , 60 % ( 15/25 ) in the 600 IU group , and 20 % ( 5/23 ) in the 800 IU group . Participants in the 800 IU group had a 72 % lower adjusted-incidence rate ratio of falls than those taking placebo over the 5 months ( rate ratio=0.28 ; 95 % confidence interval=0.11 - 0.75 ) . No significant differences were observed for the adjusted fall rates compared to placebo in any of the other supplement groups . CONCLUSION Nursing home residents in the highest vitamin D group ( 800 IU ) had a lower number of fallers and a lower incidence rate of falls over 5 months than those taking lower doses . Adequate vitamin D supplementation in elderly nursing home residents could reduce the number of falls experienced by this high falls risk group", "Abstract Aim : To observe the efficacy and safety of Rocaltrol ( calcitriol ) and /or Caltrate D ( calicum carbonate plus vitamin D ) in elderly Chinese women with osteopenia or osteoporosis . Methods : One hundred fifty Chinese women aged over 65 years with osteopenia or osteoporosis from three centers were r and omly divided into two groups . Seventy-six participants received Caltrate D as one pill daily ; the other 74 participants received 0.25 μg Caltrate D plus Rocaltrol daily . The changes in bone mineral density ( BMD ) served as primary end-points . Height changes , the presence of new vertebral fractures , muscle strength and balance were evaluated . Results : The following are the mean percentage changes ( and SD ) in BMD over 12 months : at L2-L4 , 0.83±3.88 in the Caltrate D group and 2.84±4.04 in the Rocaltrol+Caltrate D group ( P=0.003 , by ANCOVA ) ; at the femoral neck , 0.04±3.94 in the Caltrate D group and 2.01±5.45 in the Rocaltrol+Caltrate D group ( P=0.085 , by ANCOVA ) ; and in the trochanter , 1.59±4.57 in the Caltrate D group and 3.76±6.25 in the Rocaltrol+Caltrate D group ( P=0.053 , by ANCOVA ) . The st and and maximal forward reach test ( SMFRT ) was significantly enhanced in both groups during the 12 months of treatment , but no significant differences were found between these two groups . No severe adverse event related to these medications occurred throughout the study . Conclusion : Treatment with Rocaltrol plus Caltrate D or Caltrate D for 12 months in elderly Chinese postmenopausal women effectively increased BMD at the lumbar spine . Rocaltrol plus Caltrate D was more effective at the lumbar spine than Caltrate D alone ", "CONTEXT Effects of long-term calcium , with or without vitamin D , on hip bone mineral density ( BMD ) and bone turnover in sunny climates have not been reported . OBJECTIVE The aim was to evaluate the effect of vitamin D added to calcium supplementation on hip dual-energy x-ray absorptiometry BMD and calcium-related analytes . DESIGN , SETTING , AND PARTICIPANTS The study was a 5-yr r and omized , controlled , double-blind trial of 120 community-dwelling women aged 70 - 80 yr . INTERVENTIONS The interventions were 1200 mg/d calcium with placebo vitamin D ( Ca group ) or with 1000 IU/d vitamin D2 ( CaD group ) , or double placebo ( control ) . MAIN OUTCOME MEASURES Hip BMD , plasma 25-hydroxyvitamin D , biomarkers of bone turnover , PTH , and intestinal calcium absorption were measured . RESULTS Hip BMD was preserved in CaD ( -0.17 % ) and Ca ( 0.19 % ) groups but not controls ( -1.27 % ) at yr 1 and maintained in the CaD group only at yr 3 and 5 . The beneficial effects were mainly in those with baseline 25-hydroxyvitamin D levels below the median ( 68 nmol/liter ) . At yr 1 , compared with controls , the Ca and CaD groups had 6.8 and 11.3 % lower plasma alkaline phosphatase , respectively ( P urinary deoxypyridinoline to creatinine ratio , respectively ( P PTH at 3 and 5 yr cf . controls ( 27.8 and 31.3 % , P PTH levels above the median ( 3.6 pmol/liter ) . Therapy did not affect intestinal calcium absorption at high carrier loads . CONCLUSIONS Addition of vitamin D to calcium has long-term beneficial effects on bone density in elderly women living in a sunny climate , probably mediated by a long-term reduction in bone turnover rate", "In a r and omized multicenter , double-blind , double-dummy , parallel group study a comparison of the efficacy and safety of 1 μg alfacalcidol to 880 IU vitamin D plus calcium carbonate ( 1 g calcium ) once daily per os was performed on 148 postmenopausal osteoporotic Caucasian patients with normal vitamin D serum levels for 18 months . Bone mineral density ( BMD ) was measured at baseline , 12 and 18 months . Safety parameters were followed during the entire study period . Sixty-nine ( 90.8 % ) in the alfacalcidol group and 67 ( 93.1 % ) in the vitamin D group were included in the ITT analysis . Lumbar BMD in the alfacalcidol group increased by 0.017 g/cm2 ( 2.33 % ) and 0.021 g/cm2 ( 2.87 % ) from baseline ( P the vitamin D plus calcium group at both 12 and 18 months , were found to be statistically significant ( P=0.018 , 0.005 ) . A small increase of mean femoral BMD was achieved in both groups ( N.S. ) . Adverse events were similar in both groups . No significant differences were noted between the groups in serum calcium . In conclusion , alfacalcidol was found to be superior in significantly increasing lumbar BMD as compared to vitamin D plus calcium while safety characteristics were found to be similar in both treatments", "OBJECTIVES To investigate the therapeutic effect of combined use of vitamin K(2 ) and D(3 ) on vertebral bone mineral density in postmenopausal women with osteopenia and osteoporosis . SUBJECTS AND METHODS We enrolled 172 women with vertebral bone mineral density X-ray absorptiometry . In this study , we employed the criteria for diagnosis of osteopenia and osteoporosis using dual energy X-ray absorptiometry proposed by the Japan Society of Bone Metabolism in 1996 . Subjects were r and omized into four groups ( each having 43 subjects in vitamin K(2 ) therapy group , vitamin D(3 ) therapy group , vitamin K(2 ) and D(3 ) combined therapy group , or a control group receiving dietary therapy alone ) and treated with respective agents for 2 years , with bone mineral density was measured prior to therapy and after 6 , 12 , 18 , and 24 months of treatment . The bone metabolism markers analyzed were serum type 1 collagen carboxyterminal propeptide ( P1CP ) , serum intact osteocalcin , and urinary pyridinoline . Tests of blood coagulation function consisted of measurement of activated partial thromboplastin time ( APTT ) and analysis of concentrations of antithrombin III ( AT III ) , fibrinogen , and plasminogen . RESULTS Combined therapy with vitamin K(2 ) and D(3 ) for 24 months markedly increased bone mineral density ( 4.92 + /- 7.89 % ) , while vitamin K(2 ) alone increased it only 0.135 + /- 5.44 % . The bone markers measured , revealed stimulation of both bone formation and resorption activity . We observed an increase in coagulation and fibrinolytic activity that was within the normal range , suggesting that balance was maintained in the fibrinolysis-coagulation system . CONCLUSIONS Continuous combination therapy with vitamin K(2 ) and D(3 ) may be useful for increasing vertebral bone mass in postmenopausal women . Furthermore , the increase in coagulation function observed during this therapy was within the physiological range , and no adverse reactions were observed", "PURPOSE To assess the comparative effectiveness of several medications on bone mineral density , biochemical bone markers , and the incidence of vertebral fractures in postmenopausal women with osteoporosis . METHODS A total of 396 postmenopausal women , aged 50 to 75 years , were allocated r and omly to six equal-sized groups : hormone replacement therapy , etidronate , eel calcitonin , alfacalcidol , vitamin K ( menatetrenone ) , or control ( no treatment ) . Thoracic and lumbar spine radiographs , bone mineral density at the distal radius , and markers of bone turnover were assessed at baseline and every 3 months during the 2-year study . RESULTS Compared with baseline , the 2-year mean changes in bone mineral density were 2.0 % for hormone replacement therapy , -0.5 % for etidronate , 1.6 % for calcitonin , -3.6 % for alfacalcidol , -1.9 % for vitamin K , and -3.3 % for control . Seventeen ( 26 % ) of the 66 control patients developed new vertebral fractures . Compared with controls , the relative risks of vertebral fracture were 0.35 ( 95 % confidence interval [ CI ] : 0.14 to 0.83 ) for hormone replacement therapy , 0.40 ( 95 % CI : 0.17 to 0.92 ) for etidronate , 0.41 ( 95 % CI : 0.17 to 0.93 ) for calcitonin , 0.56 ( 95 % CI : 0.26 to 1.12 ) for alfacalcidol , and 0.44 ( 95 % CI : 0.20 to 0.99 ) for vitamin K. CONCLUSION We observed significant reductions in the incidence of vertebral fractures with hormone replacement therapy , etidronate , and calcitonin , and significant improvements in bone mineral density with hormone replacement therapy and calcitonin", "In a double-blind trial , 327 patients ( 57 men ) over 65 ( mean age 79.5 ) years received all possible combinations of calcium carbonate 3 g , vitamin D3 1000 iu , meth and ienone 2.5 mg and /or placebos daily for 9 months . The higher incidence of bone fractures in the placebo group was not significant . Serum calcium , phosphorus , creatinine , aspartate aminotransferase and alkaline phosphatase were followed : the greatest changes occurred with meth and ienone , which thus reduced osteoporotic activity and increased the muscular mass most effectively ; calcium carbonate had the poorest effect . Surprisingly , coronary mortality was higher among those taking all three active substances . With two treatments the increase was not significant , but when both the groups receiving a combination of any two of the treatments were compared with those taking only one or neither of these two treatments , a significant increase in coronary deaths was seen , most significant ( P less than 0.001 ) in those receiving vitamin D3 and meth and ienone", "OBJECTIVE To study the efficacy of synthetic 1,25 dihydroxyvitamin D3 ( calcitriol ) in the treatment of osteoporosis . DESIGN Two-year , double-blind , r and omized clinical trial . SETTING University medical center . PATIENTS Fifty postmenopausal women with vertebral fractures recruited by referral . INTERVENTION Calcium intake was adjusted to 25 mmol/d ( 1000 mg/d ) at baseline . Patients were then r and omized to treatment with either calcitriol or placebo . During the study , calcium intake was reduced to 15 mmol/d ( 600 mg/d ) and the dose of calcitriol was adjusted to maintain serum calcium less than 2.74 mmol/L ( less than 11.0 mg/dL ) or urine calcium less than 9.96 mmol/d ( less than 400 mg/d ) . MEASUREMENTS AND MAIN RESULTS After 2 years , the mean dose of calcitriol in the treated group was 0.62 micrograms/d . Bone mineral density of the spine increased 1.94 % with calcitriol therapy and decreased 3.92 % with placebo ( P = 0.001 ) . Total body calcium increased 0.21 % with calcitriol therapy and decreased 1.85 % with placebo ( P = 0.004 ) . Patients receiving placebo had significant decreases in spine density ( P = 0.0007 ) and total body calcium ( P = 0.0004 ) . There were no differences in vertebral fracture rates between the groups . Renal function studies were not statistically different between the groups after 2 years . CONCLUSION The treatment of postmenopausal osteoporotic women with synthetic calcitriol for 2 years was associated with increases in spine density and total body calcium . No adverse effects on renal function were seen after long-term calcitriol therapy", "CONTEXT Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures ; however , adherence to daily supplementation is typically poor . OBJECTIVE To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture . DESIGN , SETTING , AND PARTICIPANTS A double-blind , placebo-controlled trial of 2256 community-dwelling women , aged 70 years or older , considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were r and omly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years . The study concluded in 2008 . INTERVENTION 500,000 IU of cholecalciferol or placebo . MAIN OUTCOME MEASURES Falls and fractures were ascertained using monthly calendars ; details were confirmed by telephone interview . Fractures were radiologically confirmed . In a sub study , 137 r and omly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels . RESULTS Women in the cholecalciferol ( vitamin D ) group had 171 fractures vs 135 in the placebo group ; 837 women in the vitamin D group fell 2892 times ( rate , 83.4 per 100 person-years ) while 769 women in the placebo group fell 2512 times ( rate , 72.7 per 100 person-years ; incidence rate ratio [ RR ] , 1.15 ; 95 % confidence interval [ CI ] , 1.02 - 1.30 ; P = .03 ) . The incidence RR for fracture in the vitamin D group was 1.26 ( 95 % CI , 1.00 - 1.59 ; P = .047 ) vs the placebo group ( rates per 100 person-years , 4.9 vitamin D vs 3.9 placebo ) . A temporal pattern was observed in a post hoc analysis of falls . The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months ( test for homogeneity ; P = .02 ) . In the sub study , the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3 % of the sub study participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group , 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L , were approximately 90 nmol/L at 3 months , and remained higher than the placebo group 12 months after dosing . CONCLUSION Among older community-dwelling women , annual oral administration of high-dose cholecalciferol result ed in an increased risk of falls and fractures . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000658617 ; is rct n.org Identifier : IS RCT N83409867", "Summary The effect of oral 24R,25(OH)2-vitamin D3 as a prophylactic for postmenopausal bone loss was examined . Fifty-eight healthy , early postmeno-pausal women entered a double blind therapeutic trial for 2 years . After an initial examination the women were r and omized to treatment with 10 μg 24R,25(OH)2D3 daily or placebo . Participants were thereafter examined every 3 months ( nine examinations in all ) . In both groups the forearm bone mineral ( measured by single photon absorptiometry ) , the lumbar spine mineral , and the total body mineral ( measured by dual photon absorptiometry ) fell significantly and the same magnitude . Further-more , serum calcium , serum alkaline phosphatase concentration , and fasting urinary hydroxyproline were unchanged , as were the 24-hour urinary calcium excretion and the intestinal radiocalcium absorption . Our findings demonstrate that 24R,25(OH)2D3 treatment has no prophylactic effect on postmenopausal bone loss and does not alter calcium metabolic variables", "Summary Daily dosing with vitamin D often fails to achieve optimal outcomes , and it is uncertain what the target level of 25-hydroxyvitamin D should be . This study found that large loading doses of vitamin D3 rapidly and safely normalize 25OHD levels , and that monthly dosing is similarly effective after 3–5 months . With baseline 25OHD > 50 nmol/L , vitamin D supplementation does not reduce PTH levels . Introduction There is concern that vitamin D supplementation doses are frequently inadequate , and that compliance with daily medication is likely to be suboptimal . Methods This r and omized double-blind trial compares responses to three high-dose vitamin D3 regimens and estimates optimal 25-hydroxyvitamin D ( 25OHD ) levels , from changes in parathyroid hormone ( PTH ) , and procollagen type I amino-terminal propeptide ( P1NP ) in relation to baseline 25OHD . Sixty-three elderly participants were r and omized to three regimens of vitamin D supplementation : a 500,000-IU loading dose ; the loading dose plus 50,000 IU/month ; or 50,000 IU/month . Results The Loading and Loading + Monthly groups showed increases in 25OHD of 58 ± 28 nmol/L from baseline to 1 month . Thereafter , levels gradually declined to plateaus of 69 ± 5 nmol/L and 91 ± 4 nmol/l , respectively . In the Monthly group , 25OHD reached a plateau of ~80 ± 20 nmol/L at 3–5 months . There were no changes in serum calcium concentrations . PTH and P1NP were only suppressed by vitamin D treatment in those with baseline 25OHD levels of vitamin D3 rapidly and safely normalize 25OHD levels in the frail elderly . Monthly dosing is similarly effective and safe , but takes 3–5 months for plateau 25OHD levels to be reached", "The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement was developed to improve the reporting of r and omised controlled trials . It was initially published in 1996 and focused on the reporting of parallel group r and omised controlled trials . The statement was revised in 2001 , with a further up date in 2010 . A separate CONSORT statement for the reporting of abstract s was published in 2008 . In earlier papers we considered the implication s of the 2001 version of the CONSORT statement for the reporting of cluster r and omised trial . In this paper we provide up date d and extended guidance , based on the 2010 version of the CONSORT statement and the 2008 CONSORT statement for the reporting of abstract s.", "Calcium plus vitamin D ( CaD ) supplementation has a modest but significant effect on slowing loss of femoral bone mass and reducing risk of hip fractures in adherent postmenopausal women . The goal of this study was to determine if CaD supplementation influences hip structural parameters that are associated with fracture risk . We studied 1,970 postmenopausal women enrolled in the Women ’s Health Initiative r and omized controlled trial of CaD at one of three bone mineral density ( BMD ) clinical centers . Hip structural analysis software measured BMD and strength parameters on DXA scans at three regions : femoral narrow neck , intertrochanter , and shaft . R and om effects models were used to test the average differences in hip BMD and geometry between intervention and placebo . There was greater preservation of hip BMD at the narrow neck with CaD relative to placebo across 6 years of intervention . CaD also altered the underlying cross-sectional geometry at the narrow neck in the direction of greater strength , with small increases in cross-sectional area and section modulus and a decrease in buckling ratio with CaD relative to placebo . While trends at both the intertrochanter and shaft regions were similar to those noted at the narrow neck , no significant intervention effects were evident . There was no significant interaction of CaD and age or baseline calcium levels for hip structural properties . CaD supplementation is associated with modest beneficial effects on hip structural features at the narrow neck , which may explain some of the benefit of CaD in reducing hip fracture risk", "CONTEXT Bone health is influenced by the intake of both calcium and vitamin D. OBJECTIVE Our objective was to evaluate the influence of calcium and vitamin D supplementation on PTH and bone turnover . SETTING , PATIENTS , AND DESIGN : At an ambulatory research center , 159 postmenopausal healthy white women participated in this double-blind , placebo-controlled parallel , longitudinal factorial study that was 6 months in duration . INTERVENTIONS Subjects were r and omly allocated to 4 groups : 1 ) double placebo , 2 ) calcium ( 1200 mg daily ) plus placebo , 3 ) vitamin D3 ( 100 μg ) plus placebo , and 4 ) vitamin D3 and calcium . Serum and urine were collected fasting and 2 hours after a calcium load at baseline and at 3 and 6 months . MAIN OUTCOME MEASURES Serum PTH , cross-linked C-telopeptide ( CTX ) , and procollagen type I N-terminal propeptide ( P1NP ) were measured . RESULTS Before study medication , a calcium load result ed in a decline in PTH and CTX and an increase in urinary calcium excretion . Serum CTX and P1NP declined over time with calcium supplementation but did not change with increased vitamin D intake . There was a decline in PTH in the vitamin D groups in the fasting state compared with placebo . Suppression of PTH was greater after a calcium load in the vitamin D groups . A calcium load decreased PTH and CTX and raised urinary calcium . CONCLUSIONS Fasting PTH declines with vitamin D supplementation . PTH declines after calcium intake . Supplementation of the diet with 1200 mg calcium/d reduces bone turnover markers , whereas supplementation with up to100 μg vitamin D3/d does not", "CONTEXT Whether ergocalciferol ( D(2 ) ) and cholecalciferol ( D(3 ) ) are equally effective to increase and maintain serum 25-hydroxyvitamin D [ 25(OH)D ] concentration is controversial . OBJECTIVE The aim of the study was to evaluate the effect of daily and once monthly dosing of D(2 ) or D(3 ) on circulating 25(OH)D and serum and urinary calcium . DESIGN , SETTING AND PARTICIPANTS In a university clinical research setting , 64 community dwelling adults age 65 + were r and omly assigned to receive daily ( 1,600 IU ) or once-monthly ( 50,000 IU ) D(2 ) or D(3 ) for 1 yr . MAIN OUTCOME MEASURES Serum 25(OH)D , serum calcium , and 24-h urinary calcium were measured at months 0 , 1 , 2 , 3 , 6 , 9 , and 12 . Serum PTH , bone-specific alkaline phosphatase , and N-telopeptide were measured at months 0 , 3 , 6 , and 12 . RESULTS Serum 25(OH)D was less than 30 ng/ml in 40 % of subjects at baseline ; after 12 months of vitamin D dosing , levels in 19 % of subjects ( n = 12 , seven receiving daily doses and five monthly doses ) remained low , despite compliance of more than 91 % . D(2 ) dosing increased 25(OH)D(2 ) but produced a decline ( P 25(OH)D(3 ) . Substantial between-individual variation in 25(OH)D response was observed for both D(2 ) and D(3 ) . The highest 25(OH)D observed was 72.5 ng/ml . Vitamin D administration did not alter serum calcium , PTH , bone-specific alkaline phosphatase , N-telopeptide , or 24-h urine calcium . CONCLUSIONS Overall , D(3 ) is slightly , but significantly , more effective than D(2 ) to increase serum 25(OH)D. One year of D(2 ) or D(3 ) dosing ( 1,600 IU daily or 50,000 IU monthly ) does not produce toxicity , and 25(OH)D levels of less than 30 ng/ml persist in approximately 20 % of individuals . Substantial between-individual response to administered vitamin D(2 ) or D(3 ) is observed", "In a 5-yr r and omized prospect i ve study we examined the treatment effect of estrogen replacement therapy/hormone replacement therapy ( ERT/HRT ) , calcitriol , ERT/HRT and calcitriol , or placebo for 3 yr and the effect of discontinuation of therapy for 2 more yr on bone mineral density ( BMD ) , calciotropic hormones , markers of bone remodeling , and calcium absorption in 489 elderly women . The treatment phase of the study was double-blinded . After discontinuing therapy for 2 yr , there was rapid bone loss in all 3 treatment groups , and most of the decrease in BMD occurred in the first year . In the ERT/HRT group , spine BMD increased 5.5 % in yr 3 , decreased 3.2 % in yr 4 , and decreased 0.7 % in yr 5 ; femoral neck BMD increased 3.7 % in yr 3 , decreased 2.5 % in yr 4 , and decreased 0.4 % in yr 5 ; total body BMD increased 2.1 % in yr 3 , decreased 1.4 % in yr 4 , and decreased 0.6 % in yr 5 . In the combination group , spine BMD increased 7.1 % in yr 3 , decreased 4.3 % in yr 4 , and decreased 0.3 % in yr 5 ; femoral neck BMD increased 4.5 % in yr 3 , decreased 3.0 % in yr 4 , and decreased 0.01 % in yr 5 ; total body BMD increased 2.2 % in yr 3 , decreased 1.5 % in yr 4 , and decreased 0.6 % in yr 5 . In the calcitriol group , spine BMD increased 1.8 % in yr 3 , decreased 1.8 % in yr 4 , and showed no change in yr 5 ; femoral neck BMD increased 0.2 % in yr 3 , decreased 0.2 % in yr 4 , and decreased 0.6 % in yr 5 ; total body BMD decreased 0.4 % in yr 3 , decreased 0.6 % in yr 4 , and decreased 0.4 % in yr 5 . Compared with placebo , all treated groups at yr 5 had significantly higher total body BMD ; only the combination group had significantly higher spine BMD ( 3.4 % ; P total hip BMD ( 2.4 % ; P only spine BMD in the combination group was significantly higher ( 2.6 % ; P calcium absorption and the decrease in serum PTH levels in the calcitriol groups were reversed after discontinuation of treatment , and the decrease in bone markers was reversed in the hormone-treated groups . These results suggest that discontinuation of ERT/HRT and /or calcitriol therapy in elderly women leads to a decrease in much of the BMD gained on treatment ; however , in the combination group there was a statistically significant residual effect on spine BMD", "Radiographically detected vertebral fractures ( hereafter referred to as vertebral fractures ) are a hallmark of postmenopausal osteoporosis and an important end point in clinical trials of osteoporosis treatment . Women with vertebral fractures have low bone mass compared with women without these fractures and , independently of bone mass , have an increased risk for additional vertebral and other fractures [ 1 - 4 ] . Vertebral fractures are common : Five percent of 50-year-old white women and 25 % of 80-year-old women have had at least one vertebral fracture [ 5 ] . Surprisingly , however , the manner in which vertebral fractures affect health remains uncertain . Cross-sectional studies in community-derived sample s of older women have demonstrated only a modest association [ 6 - 8 ] or no association [ 9 - 11 ] between prevalent vertebral fractures and back pain or disability . Cross-sectional studies do not distinguish more recent fractures from older vertebral fractures and may fail to capture transient increases in pain or disability [ 12 ] , a limitation that may underestimate the clinical effect of these fractures [ 13 ] . Back pain is common among elderly women [ 14 ] , and frequent causes of back pain , such as degenerative disc disease , facet joint osteoarthritis , spinal stenosis , and scoliosis , may obscure the impact of vertebral fracture . Only about one third of new vertebral fractures come to medical attention [ 15 , 16 ] , suggesting that most vertebral fractures are asymptomatic . However , attitudes toward back pain in older women and access to health care may also play a role in determining whether vertebral fractures come to medical attention . We examined the effect of incident vertebral fractures on back pain and back-related functional limitations in a large community-based sample of elderly women who underwent serial spinal radiography and annual assessment s of back pain and disability over the same period . Methods Participants Study patients were participants in the Study of Osteoporotic Fractures , a cohort recruited from population -based listings in four U.S. metropolitan areas . Details of the design of this study are published elsewhere [ 17 ] . Lateral spine radiographs were obtained for 9677 white women between the ages of 65 and 99 years ( median age , 70 years ) who underwent baseline examination between 1986 and 1988 . Repeated spinal radiographs suitable for morphometry were obtained for 7223 women ( 75 % of the original cohort ) at a follow-up clinic visit held an average of 3.7 years ( range , 1.3 to 5.1 years ) later . All participants gave informed consent . Vertebral Morphometry Lateral radiographs of the thoracic and lumbar spine were obtained in accordance with current guidelines [ 18 ] . Quantitative vertebral morphometry was performed using six-point digitization as described elsewhere [ 3 , 19 ] to calculate the anterior ( Ha ) , mid- ( Hm ) , and posterior ( Hp ) height for each vertebral body from T4 to L4 . A system of triage of radiographs , described elsewhere [ 3 , 20 ] , was used to reduce the number of radiographs requiring morphometric measurements . Briefly , trained technicians separated sets of radiographs into normal , uncertain , or probably fractured groups on the basis of a limited semiquantitative grading scheme that categorized women by the most abnormal vertebral level [ 20 ] . Uncertain grade s were further categorized by the study radiologist as normal or probably fractured . Morphometry was done on the radiograph pairs that were categorized as probably fractured ( 42 % ) . In a r and om sample of 503 women whose radiographs were triaged and then digitized , triage missed no incident fractures according to the study definition . Definition of Vertebral Fracture A vertebra was classified as having a prevalent fracture on the baseline radiograph if any of the following ratios were more than 3 SDs ( > 4 SDs for severe fractures ) below the normal mean for that vertebral level : ( Ha/Hp ) , ( Hm/Hp ) , or a combination of ( H/H [ ] 1 ) and ( Hai/Hai 1 ) [ 3 , 21 ] . A new ( incident ) fracture was identified if any of the three vertebral heights ( Ha , Hm , or Hp ) on follow-up radiographs decreased by 20 % or more and by at least 4 mm compared with the baseline height . Incident fractures identified by morphometry were review ed by a radiologist to exclude imaging artifacts or such conditions as osteophytosis and Scheuermann disease ; 7 % of vertebrae meeting the morphometric criteria for incident fracture were reclassified as not fractured . Incident Clinical Fractures We used previously described methods [ 22 ] to assess the occurrence of clinical fractures of any bone during follow-up . Women were considered to have a clinical vertebral fracture if they reported a new diagnosis of spinal fracture and a clinical radiology report confirmed that a vertebral fracture was present . Measurements of Pain , Disability , and Limited Activity We evaluated outcome measures by using a previously described question naire [ 7 , 23 ] that asked about back pain and back-related disability in the past 12 months and the number of days of limited activity due to back pain . The question naire was administered at baseline and at three annual follow-up contacts held before assessment of vertebral fractures . The third follow-up contact coincided with follow-up radiography . Back pain was assessed on scales of frequency ( 0 , never or rarely ; 1 , some of the time ; 2 , most of the time ; or 3 , all of the time ) and severity ( 0 , no pain ; 1 , mild pain ; 2 , moderate pain ; or 3 , severe pain ) . The two pain questions had high internal consistency ( Cronbach = 0.81 ) and were summed for a total score that could range from 0 to 6 . We defined clinical ly significant back pain as pain that was experienced most or all of the time or pain that was moderate or severe . Women without significant back pain at baseline were considered to have increased back pain if clinical ly significant pain had developed between any follow-up contacts . For women with clinical ly significant back pain at baseline , increased back pain was defined as an increase in total pain score of at least two points . Both types of increase had a similar association with incident fractures and thus were combined for a single outcome . Back-related disability was assessed with questions about the degree of difficulty ( 0 , no difficulty ; 1 , some difficulty ; 2 , much difficulty ; or 3 , unable to perform activity ) in six activities of daily living that involved the back ( bending down to pick up light-weight objects , lifting a 10-pound object from the floor , reaching for objects just above the head , putting on socks or stockings , getting in and out of an automobile , and st and ing for 2 hours ) . These measures were combined in a back-related disability score ranging from 0 to 18 . As reported elsewhere [ 7 ] , this scale has high internal consistency ( Cronbach = 0.82 ) and is highly correlated ( Spearman r = 0.73 ) with a more extensive instrument used to assess disability caused by low back pain [ 24 ] . We defined clinical ly significant disability as much difficulty or unable in one or more of the six activities . Women without significant disability at baseline were considered to have increased disability if clinical ly significant disability had developed between any follow-up contacts . For women with clinical ly significant disability at baseline , increased disability was defined as an increase in disability score of at least three points . Both types of increase had a similar association with incident fractures and thus were combined for a single outcome . We also asked participants if they had limited their activities because of back pain since the last contact ; if the answer was yes , we asked for the number of days they had stayed in bed and the number of days on which activity was limited ( not including days in bed ) because of back pain . Questions were adapted from previous surveys [ 25 , 26 ] . For all follow-up contacts , we summed the number of days of bed rest and , in a separate measure , the number of days of limited activity ; we then divided these numbers by the total years of follow-up to estimate the average number of affected days per year . Other Measurements The baseline question naire assessed potential confounding factors that may be associated with the risk for incident vertebral fracture and with back pain or disability , including smoking ( current or past smoker ) ; inactivity , defined as walking less than one block daily ( yes or no ) ; a previous physician diagnosis of osteoporosis or spinal fracture ( yes or no ) ; current use of estrogen ( yes or no ) ; hip pain in the past 12 months ( yes or no ) ; and height at 25 years of age . At the baseline examination , we assessed height and weight and calculated body mass index ( kg/m2 ) . We assessed grip strength by using an isometric dynamometer ( Jamar Hydraulic H and Dynamometer , JA Preston , Jackson , Mississippi ) at baseline and at the follow-up examination and calculated change in grip strength between the two measurements . A r and om sample of 16 % of baseline spine radiographs was assessed for spinal disc degeneration by using previously published methods [ 27 ] . Statistical Analysis Unless otherwise indicated , analyses were done separately in groups stratified by the presence of one or more baseline prevalent vertebral fractures . Descriptive and bivariate associations were assessed by using the t-test for continuous variables and the chi-square test for dichotomous variables . The association between incident vertebral fractures and dichotomous outcomes ( increased back pain and increased back disability ) was analyzed with logistic regression techniques . We analyzed the association of incident vertebral fracture with days of bed rest and days of limited activity per year by using Poisson regression . The distribution of days of bed rest ( mean SD , 0.44 5.15 ) and limited-activity days ( 16.3 53.7 ) indicate that considerable overdispersion is present . Poisson regression allowing for this overdispersion provides a good estimation and inferential scheme [", "STUDY OBJECTIVE To determine if calcitriol is an effective treatment in postmenopausal osteoporosis . DESIGN Double-blind , r and omized clinical trial of 2 years ' duration . SETTING University medical center with patients recruited by media announcements . PATIENTS Eighty-six postmenopausal women with vertebral compression fractures . INTERVENTIONS Patients were treated with calcitriol or placebo . Mean dose was 0.43 micrograms/d . Dietary calcium was 1000 mg/d ( 24.9 mmol/d ) . The medication dose and dietary calcium were adjusted for hypercalciuria or hypercalcemia . MEASUREMENTS AND MAIN RESULTS No significant differences between placebo and control groups were seen in the percent change in total body calcium ( 0.4 % + /- 1.0 compared with 0.0 % + /- 0.9 ) , single photon absorptiometry ( -0.5 % + /- 1.2 compared with -3.1 % + /- 0.9 ) or dual photon absorptiometry ( 0.0 % + /- 1.7 compared with -1.0 % + /- 2.2 ) . New fractures were seen in 16 % of the placebo group and 26 % of the calcitriol groups , so the difference in percent fractures was 10 % ( 95 % CI , -5.7 % to 25.7 % ) . Bone biopsies did not show changes in either group . The calcitriol group had significantly higher serum and urine calcium values , but renal function was not worse than in the placebo group . CONCLUSIONS Calcitriol is not an effective treatment for established postmenopausal osteoporosis", "Summary The Osteoporosis Risk Factor and Prevention-Fracture Prevention Study ( OSTPRE-FPS ) was a r and omized population -based open trial ( n = 593 ) . The supplementation group ( n = 287 ) received daily cholecalciferol 800 IU + calcium 1,000 mg for 3 years while the control group ( n = 306 ) received neither supplementation nor placebo . Daily vitamin D and calcium supplementation have a positive effect on the skeleton in ambulatory postmenopausal women . Introduction Vitamin D deficiency is common in the elderly , and vitamin D levels are associated with low bone mineral density ( BMD ) . The working hypothesis was that vitamin D and calcium supplementation could prevent bone loss in ambulatory postmenopausal women . Methods The OSTPRE-FPS was a r and omized population -based open trial with a 3-year follow-up in 3,432 women ( aged 66 to 71 years ) . A r and omly selected sub sample of 593 subjects underwent BMD measurements . The supplementation group ( n = 287 ) received daily cholecalciferol 800 IU + calcium 1,000 mg for 3 years while the control group ( n = 306 ) received neither supplementation nor placebo . Results In the intention-to-treat analysis , total body BMD ( n = 362 ) increased significantly more in the intervention group than in the control group ( 0.84 % vs. 0.19 % , p = 0.011 ) . The BMD change differences at the lumbar spine ( p = 0.372 ) , femoral neck ( p = 0.188 ) , trochanter ( p = 0.085 ) , and total proximal femur ( p = 0.070 ) were statistically nonsignificant . Analyses in compliant women ( ≥80 % of use ) result ed in stronger and statistically significant effects at the total body and femoral regions . Conclusion Daily vitamin D and calcium supplementation have a positive effect on the skeleton in ambulatory postmenopausal women with adequate nutritional calcium intake", "Abstract Objectives : The authors conducted a r and omized controlled trial to clarify the efficacy and safety of alendronate plus alfacalcidol versus alendronate alone in a clinical setting . Research design and methods : Eligible patients were postmenopausal women with severe osteoporosis who were aged 70 years or older and had several risk factors for incident fractures . The primary endpoint was prevention of incident fractures , and the anti-fracture efficacy was evaluated in relation to the baseline serum 25(OH)D level . Results : A total of 2164 patients were r and omized to alendronate plus alfacalcidol ( combination therapy ) or alendronate alone ( monotherapy ) . Although the overall difference in the incidence of vertebral fracture between the two groups was not significant , the combination therapy group had a significantly reduced risk of vertebral fractures after the first 6 months ( HR , 0.53 ) . In subgroup analyses , the combination therapy group was superior in the strata of number of prevalent vertebral fractures of ≥2 ( HR , 0.51 ) and grade 3 of prevalent vertebral fractures ( HR , 0.55 ) . The rate of non-vertebral weight-bearing bone fractures was significantly lower in the combination therapy group than in the monotherapy group during the follow-up period ( HR , 0.31 ) . A lower baseline 25(OH)D level was associated with a higher incidence of non-vertebral weight-bearing bone fractures ( HR , 3.42 ) despite alendronate use . Although one patient given the combination therapy had mild hypercalcemia , serious hypercalcemia and unknown adverse events were not encountered . Because of the limitations presented in this study , these results may not apply to female patients with longer than 2 years of treatments , and to male osteoporosis patients . Conclusions : The combination therapy was no more effective for overall vertebral fracture prevention . However , subgroup analysis has shown that it was more effective for fracture prevention in patients with severe vertebral deformity , multiple prevalent vertebral fractures , and for non-vertebral weight-bearing bone fracture prevention", "We evaluated low-dose calcitriol ( 0.25 microgram b.i.d . ) in combination with 1 g of supplemental calcium therapy as treatment for osteopenic women over 60 years of age ( n = 4 ) . Control patients ( n = 6 ) received ergocalciferol ( 50,000 units twice a week ) and 1 g of supplemental calcium . Bone biopsies and CT-determined bone mineral density were done initially and after 1 year of therapy . Bone mineral density increased from 77 + /- 18 to 88 + /- 9 mg/ml ( NS ) in the calcitriol-treated group and from 87 + /- 13 to 112 + /- 30 mg/ml ( NS ) in the ergocalciferol-treated group . There was also no significant change in bone volume , as determined by bone biopsy in either group . No compression fractures occurred in either treatment group . After 1 year of therapy , urinary calcium excretion was increased significantly above that observed in age-matched untreated women . Creatinine clearance did not change significantly . Hypercalcemia was rare . In summary , we found calcitriol was not superior to ergocalciferol in preventing progressive bone loss and fractures . Both therapies were associated with significant hypercalciuria", "Abstract Objective : To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community . Design : R and omised double blind controlled trial of 100 000 IU oral vitamin D3 ( cholecalciferol ) supplementation or matching placebo every four months over five years . Setting and participants : 2686 people ( 2037 men and 649 women ) aged 65 - 85 years living in the general community , recruited from the British doctors register and a general practice register in Suffolk . Main outcome measures : Fracture incidence and total mortality by cause . Results : After five years 268 men and women had incident fractures , of whom 147 had fractures in common osteoporotic sites ( hip , wrist or forearm , or vertebrae ) . Relative risks in the vitamin D group compared with the placebo group were 0.78 ( 95 % confidence interval 0.61 to 0.99 , P=0.04 ) for any first fracture and 0.67 ( 0.48 to 0.93 , P=0.02 ) for first hip , wrist or forearm , or vertebral fracture . 471 participants died . The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 ( 0.74 to 1.06 , P=0.18 ) . Findings were consistent in men and women and in doctors and the general practice population . Conclusion : Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community . What is already known in this topic Vitamin D and calcium supplements are effective in preventing fractures in elderly women Whether isolated vitamin D supplementation prevents fractures is not clear What this paper adds Four monthly oral supplementation with 100 000 IU vitamin D reduces fractures in men and women aged over 65 living in the general community Total fracture incidence was reduced by 22 % and fractures in major osteoporotic sites by 33", "Background There remains uncertainty regarding the appropriate therapeutic management of hip fracture patients . The primary aim of our study was to examine whether large loading doses in addition to daily vitamin D offered any advantage over a simple daily low-dose vitamin D regimen for increasing vitamin D levels . Methods In this r and omized controlled study , patients over age 50 with an acute fragility hip fracture were enrolled from two hospital sites in Ontario , Canada . Participants were r and omized to one of three loading dose groups : placebo ; 50,000 IU vitamin D2 ; or 100,000 IU D2 . Following a placebo/loading dose , all patients received a daily tablet of 1,000 IU vitamin D3 for 90 days . Serum 25-hydroxy vitamin D ( 25-OHD ) was measured at baseline , discharge from acute care ( approximately 4-weeks ) , and 3-months . Results Sixty-five patients were enrolled in the study ( 44 % male ) . An immediate rise in 25-OHD occurred in the 100,000 group , however there were no significant differences in 25-OHD between the placebo , 50,000 and 100,000 loading dose groups after 4-weeks ( 69.3 , 84.5 , 75.6 nmol/L , p = 0.15 ) and 3-months ( 86.7 , 84.2 , 73.3 nmol/L , p = 0.09 ) , respectively . At the end of the study , approximately 75 % of the placebo and 50,000 groups had reached the target therapeutic range ( 75 nmol/L ) , and 44 % of the 100,000 group . Conclusions In correcting vitamin D insufficiency/deficiency in elderly patients with hip fracture , our findings suggest that starting with a lower daily dose of Vitamin D3 achieved similar results as providing an additional large loading dose of Vitamin D2 . At the end of the study , all three groups were equally effective in attaining improvement in 25-OHD levels . Given that a daily dose of 1,000 IU vitamin D3 ( with or without a loading dose ) result ed in at least 25 % of patients having suboptimal vitamin D status , patients with acute hip fracture may benefit from a higher daily dose of vitamin D.Trial registration Clinical Trials #", "Background R and omised , placebo-controlled trials are needed to provide evidence demonstrating safe , effective interventions that reduce falls and fractures in the elderly . The quality of a clinical trial is dependent on successful recruitment of the target participant group . This paper documents the successes and failures of recruiting over 2,000 women aged at least 70 years and at higher risk of falls or fractures onto a placebo-controlled trial of six years duration . The characteristics of study participants at baseline are also described for this study . Methods The Vital D Study recruited older women identified at high risk of fracture through the use of an eligibility algorithm , adapted from identified risk factors for hip fracture . Participants were r and omised to orally receive either 500,000 IU vitamin D3 ( cholecalciferol ) or placebo every autumn for five consecutive years . A variety of recruitment strategies were employed to attract potential participants . Results Of the 2,317 participants r and omised onto the study , 74 % ( n = 1716/2317 ) were consented onto the study in the last five months of recruiting . This was largely due to the success of a targeted mail-out . Prior to this only 541 women were consented in the 18 months of recruiting . A total of 70 % of all participants were recruited as a result of targeted mail-out . The response rate from the letters increased from 2 to 7 % following revision of the material by a public relations company . Participant demographic or risk factor profile did not differ between those recruited by targeted mail-outs compared with other methods . Conclusion The most successful recruitment strategy was the targeted mail-out and the response rate was no higher in the local region where the study had extensive exposure through other recruiting strategies . The strategies that were labour-intensive and did not result in successful recruitment include the activities directed towards the GP medical centres . Comprehensive recruitment programs employ overlapping strategies simultaneously with ongoing assessment of recruitment rates . In our experience , and others direct mail-outs work best although rights to privacy must be respected . Trial registration IS RCT N83409867 and ACTR12605000658617", "Abstract Objective To assess whether supplementation with calcium and cholecaliferol ( vitamin D3 ) reduces the risk of fracture in women with one or more risk factors for fracture of the hip . Design Pragmatic open r and omised controlled trial . Setting Practice nurse led clinics in primary care . Participants 3314 women aged 70 and over with one or more risk factors for hip fracture : any previous fracture , low body weight ( Intervention Daily oral supplementation using 1000 mg calcium with 800 IU cholecaliferol and information leaflet on dietary calcium intake and prevention of falls , or leaflet only ( control group ) . Main outcome measures Primary outcome measure was all clinical fractures and secondary outcome measures were adherence to treatment , falls , and quality of life ( measured with the SF-12 ) . Results 69 % of the women who completed the follow-up question naire at 24 months were still taking supplements ( 55 % with inclusion of r and omised participants known to be alive ) . After a median follow-up of 25 months ( range 18 to 42 months ) , clinical fracture rates were lower than expected in both groups but did not significantly differ for all clinical fractures ( odds ratio for fracture in supplemented group 1.01 , 95 % confidence interval 0.71 to 1.43 ) . The odds ratio for hip fracture was 0.75 ( 0.31 to 1.78 ) . The odds of a woman having a fall at six and 12 months was 0.99 and 0.98 , respectively . Quality of life did not significantly differ between the groups . Conclusion We found no evidence that calcium and vitamin D supplementation reduces the risk of clinical fractures in women with one or more risk factors for hip fracture . Registration IS RCT N26118436 , controlled trials registry", "BACKGROUND vitamin D supplementation reduces the incidence of fractures in older adults . This may be partly mediated by effects of vitamin D on neuromuscular function . OBJECTIVE to determine the effects of vitamin D supplementation on aspects of neuromuscular function known to be risk factors for falls and fractures . DESIGN r and omised , double-blind , placebo-controlled study . SETTING falls clinic taking referrals from general practitioners and accident and emergency department . SUBJECTS 139 ambulatory subjects ( > /=65 years ) with a history of falls and 25-hydroxyvitamin D ( 25OHD ) INTERVENTION patients were r and omised to receive a single intramuscular injection of 600,000 i.u . ergocalciferol or placebo . OUTCOME MEASURES assessment s including biochemistry , postural sway , choice reaction time ( CRT ) , aggregate functional performance time ( AFPT ) , and quadriceps strength were carried out at baseline and 6 months post-intervention . RESULTS baseline characteristics were comparable between both groups . 25OHD in the treatment group increased significantly at 6 months . AFPT deteriorated in the control group and improved in the intervention group , representing a significant difference between groups ( + 6.6 s versus -2.0 s , t = 2.80 , P CRT ( -0.06 s versus + 0.41 s , t = -2.52 , P postural sway ( + 0.0025 versus -0.0138 , t = 2.35 , P muscle strength change between groups ( -10 N versus -2 N , t = -1.26 , ns ) . A significant correlation between change in AFPT and change in 25OHD levels was observed ( r = 0.19 , P = 0.03 ) . There was no significant difference in the number of falls ( 0.39 versus 0.24 , t = 1.08 , P = 0.28 ) or fallers ( 14 versus 11 , P = 0.52 ) between two groups . CONCLUSIONS vitamin D supplementation , in fallers with vitamin D insufficiency , has a significant beneficial effect on functional performance , reaction time and balance , but not muscle strength . This suggests that vitamin D supplementation improves neuromuscular or neuroprotective function , which may in part explain the mechanism whereby vitamin D reduces falls and fractures", "Aims : To examine the effect of combined calcium and vitamin D3 supplementation on bone mineral density ( BMD ) in patients with chronic kidney disease ( CKD ) . Methods : We performed a post-hoc analysis of the DECALYOS II , a 2-year r and omized , double-blind , placebo-controlled study of 610 women r and omized to : calcium-vitamin D3 fixed combination , calcium plus vitamin D3 separate combination , or placebo . Both active treatment groups received the same daily amount of calcium ( 1,200 mg ) and vitamin D3 ( 800 IU ) . BMD of the distal radius was measured by single X-ray absorptiometry at baseline , 12 and 24 months . Results : At baseline 47.2 % , 36.4 % and 16.4 % of the study population had an eGFR ≥ 60 , 45 – 59 , and , respectively . Both active regimens vs. placebo markedly increased serum 25-hydroxyvitamin D levels from baseline in all eGFR groups ( p on distal radius BMD ( p = 0.005 ) , with the active treatment groups showing a lower rate of BMD loss when compared to the placebo group . The effects of the intervention on BMD did not differ significantly according to baseline eGFR ( interaction p > 0.22 for all time points ) . Conclusion : Combined calcium and vitamin D3 supplementation was effective in reducing rate of BMD loss in women with moderate CKD", "Abstract : Hormone replacement therapy ( HRT ) prevents postmenopausal bone loss and fractures . However , the occurrence of women with no bone response to HRT has not been widely examined . We identified the densitometric nonresponders to long-term HRT and investigated some characteristics and biochemical variables as possible predictors of densitometric nonresponse in postmenopausal women . The study population was a sub sample of the Kuopio Osteoporosis Study ( n= 14.220 ) . A total of 464 early postmenopausal women were r and omized into four treatment groups : ( 1 ) HRT ( sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate ) ; ( 2 ) vitamin D3 ; ( 3 ) HRT + Vitamin D3 combined ; and ( 4 ) placebo . In this study , the data from HRT and placebo groups were analyzed . Lumbar ( L2–4 ) and femoral neck bone mineral density ( BMD ) were determined by dual-energy X-ray absorptiometry ( DXA ) at baseline and after 5 years of treatment . A densitometric nonresponder was defined as a woman whose 5-year BMD change was similar to the mean BMD change ( + 95 % CI ) of the placebo group or worse . Altogether , 74 women in the HRT group and 104 women in the placebo group complied with the treatment . According to spinal BMD analysis , 11 % of the women were classified as densitometric nonresponders ; the corresponding proportion for femoral BMD analysis was 26 % . Both smoking ( p= 0.003 ) and low body weight ( p= 0.028 ) were significant risk factors for densitometric nonresponse to HRT . After 6 months of treatment the densitometric nonresponders ( hip ) had a significantly higher mean serum follicle stimulating hormone ( FSH ) level ( p= 0.038 ) and lower increases in serum estradiol levels ( p= 0.006 ) than the densitometric responders . The mean changes in serum FSH and alkaline phosphatase levels were significantly lower among the densitometric nonresponders ( spine ) than responders ( p= 0.043 and 0.017 , respectively ) . In conclusion , this prospect i ve study shows that especially current smokers and women with low body weight are at increased risk of poor bone response to HRT . Repeated serum FSH , estradiol and alkaline phosphatase measurements during the first months of long-term HRT may be helpful in identifying the women with no bone response to HRT", "The effects of 1α-hydroxyvitamin D3 [ 1α(OH)D3 ] on bone mineral density , fracture incidence , and bone metabolism were evaluated by a double-blind , placebo-controlled study . Eighty postmenopausal osteoporotic Japanese women ( 71.9±7.3 years , mean±SD ) were r and omly assigned to 1 μg of 1α(OH)D3 daily or inactive placebo for 1 year . All patients were given supplemental calcium ( 300 mg of elemental calcium daily ) . Lumbar ( L2–L4 ) bone mineral density ( BMD ) determined by dual energy X-ray absorptiometry increased 0.65 % with 1α(OH)D3 treatment and decreased 1.14 % with placebo ( P=0.037 ) . BMD in both the femoral neck and Ward 's triangle did not yield any significant differences between the two groups , whereas trochanter BMD in the 1α(OH)D3-treated group increased 4.20 % and decreased 2.37 % with placebo ( P=0.055 ) . X-ray analysis demonstrated that new vertebral fractures occurred in two patients with 1α(OH)D3 and in seven patients with placebo . The vertebral fracture rate in the treated group was significantly less ( 75/1000 patient years ) than in the control group ( 277/1000 patient years ; P=0.029 ) . Hypercalcemia ( 12.1 mg/100 ml ) occurred in one patient receiving 1α(OH)D3 ; however , the serum calcium level in this patient promptly decreased to the reference range after cessation of the treatment . There were no significant changes in serum creatinine level in either group . A significant increase in urinary excretion of calcium was found but there was no significant change in urinary excretion of hydroxyproline in the treated group . The serum level of bone-derived alkaline phosphatase activity significantly decreased by−26±26 ( mU/ml ) after the treatment ( P=0.003 ) . These results indicate that 1α(OH)D3 treatment is effective for maintaining trabecular bone mass and prevents further vertebral fractures without any serious adverse effects in postmenopausal osteoporosis ", "BACKGROUND Many risk factors for hip fractures have been suggested but have not been evaluated in a comprehensive prospect i ve study . METHODS We assessed potential risk factors , including bone mass , in 9516 white women 65 years of age or older who had had no previous hip fracture . We then followed these women at 4-month intervals for an average of 4.1 years to determine the frequency of hip fracture . All reports of hip fractures were vali date d by review of x-ray films . RESULTS During the follow-up period , 192 women had first hip fractures not due to motor vehicle accidents . In multivariable age-adjusted analyses , a maternal history of hip fracture doubled the risk of hip fracture ( relative risk , 2.0 ; 95 percent confidence interval , 1.4 to 2.9 ) , and the increase in risk remained significant after adjustment for bone density . Women who had gained weight since the age of 25 had a lower risk . The risk was higher among women who had previous fractures of any type after the age of 50 , were tall at the age of 25 , rated their own health as fair or poor , had previous hyperthyroidism , had been treated with long-acting benzodiazepines or anticonvulsant drugs , ingested greater amounts of caffeine , or spent four hours a day or less on their feet . Examination findings associated with an increased risk included the inability to rise from a chair without using one 's arms , poor depth perception , poor contrast sensitivity , and tachycardia at rest . Low calcaneal bone density was also an independent risk factor . The incidence of hip fracture ranged from 1.1 ( 95 percent confidence interval , 0.5 to 1.6 ) per 1,000 woman-years among women with no more than two risk factors and normal calcaneal bone density for their age to 27 ( 95 percent confidence interval , 20 to 34 ) per 1,000 woman-years among those with five or more risk factors and bone density in the lowest third for their age . CONCLUSIONS Women with multiple risk factors and low bone density have an especially high risk of hip fracture . Maintaining body weight , walking for exercise , avoiding long-acting benzodiazepines , minimizing caffeine intake , and treating impaired visual function are among the steps that may decrease the risk", "In a prospect i ve , r and omized study , 66 osteoporotic postmenopausal women ( mean age , 67 years ) were scheduled to receive either alfacalcidol 0.25 microgram twice daily together with calcium 500 mg twice daily ( treatment group , n = 24 ) or placebo twice daily with calcium 500 mg twice daily ( control group , n = 42 ) for three years . In the treatment group , bone mineral content at the distal radius may have increased by 2 % compared to a significant decrease of 7.8 % in the control group . The difference between the two groups was also significant . Since the dose of alfacalcidol and calcium remained unadjusted , frequent hypercalciuria , as well as occasional mild , transient elevations of serum calcium , were observed in the treatment group . No changes in serum creatinine levels or creatinine clearance throughout the study were observed . The two groups did not differ with respect to the frequency of clinical side effects , which were mainly gastrointestinal and probably related to the calcium supplementation . Alfacalcidol and calcium may prevent further bone loss in women suffering from postmenopausal osteoporosis", "Although vitamin D supplementation in the frail elderly improves calcium absorption , suppresses parathyroid hormone , decreases bone loss and reduces the risk of fractures , such treatment may be ineffective in patients with vertebral osteoporosis , because of impaired vitamin D metabolism or resistance to the action of vitamin D metabolites on the bowel . We have therefore performed a r and omized , single masked study comparing the effects of alfacalcidol treatment ( 0.25 µg twice daily ) and vitamin D2 supplementation ( 500 - 1000 units daily ) on calcium absorption and bone turnover in 46 elderly women ( median age 69 years , range 64–79 years ) with radiological evidence of vertebral fractures . Serum 25-hydroxyvitamin D increased significantly after 3 and 6 months of treatment with vitamin D2 ( p receiving alfacalcidol . Serum 1,25-dihydroxyvitamin D did not change significantly in either group over the study period . Fractional45Ca absorption increased after 3 months of treatment with alfacalcidol ( p with vitamin D2 . There was also a reduction in plasma intact parathyroid hormone and serum alkaline phosphatase after 6 months of treatment with alfacalcidol ( p receiving vitamin D2 . Our study shows that vitamin D2 supplementation is ineffective in stimulating calcium absorption in elderly women with vertebral osteoporosis . By increasing calcium absorption in such patients , alfacalcidol may prove more effective than vitamin D in the management of vertebral osteoporosis", "A controlled therapeutic trial on seventy‐four 70‐year‐old women was carried out with the purpose of finding the optimal treatment for post menopausal osteoporosis . The bone mineral content ( BMC ) was measured by 125I‐photonabsorptiometry at two sites in the distal part of the forearms , where the trabecular/cortical ratio is 0·25 and 1·5 , respectively . Radiographs were done on the right h and to measure the metacarpal bone mass ( cortical area/total area = CA/TA )", "OBJECTIVE Vitamin D supplementation is suggested to reduce the risk of falls among ambulatory or institutionalized elderly subjects . The present study was undertaken to address the reduced risk of falls and hip fractures in patients with long-st and ing stroke by vitamin D supplementation . METHODS Ninety-six elderly women with poststroke hemiplegia were followed for two years . Patients were r and omly assigned to one of the two groups , and 48 patients received 1,000 IU ergocalciferol daily , and the remaining 48 received placebo . The number of falls per person and incidence of hip fractures were compared between the two groups . Strength and tissue ATPase of skeletal muscles on the nonparetic side were assessed before and after the study . RESULTS At baseline , serum 25-hydroxyvitamin D levels were in the deficient range ( vitamin D treatment enhanced serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels . Vitamin D treatment accounted for a 59 % reduction in falls ( 95 % CI , 28 - 81 % ; p = 0.003 ) . There were increases in the relative number and size of type II muscle fibers and improved muscle strength in the vitamin D-treated group . Hip fractures occurred in 4 of 48 placebo group and 0 in 48 vitamin D2 group during the 2-year study period ( log-rank , p = 0.049 ) . CONCLUSION Vitamin D may increase muscle strength by improving atrophy of type II muscle fibers , which may lead to decreased falls and hip fractures", "UNLABELLED Dietary supplementation with vitamin K(1 ) , with vitamin D(3 ) and calcium or their combination , was examined in healthy older women during a 2-year , double-blind , placebo-controlled trial . Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius . INTRODUCTION The putative beneficial role of high dietary vitamin K(1 ) ( phylloquinone ) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind , placebo-controlled trial in healthy Scottish women > or = 60 years of age . MATERIAL S AND METHODS Healthy , nonosteoporotic women ( n = 244 ) were r and omized to receive either ( 1 ) placebo , ( 2 ) 200 microg/day vitamin K(1 ) , ( 3 ) 10 microg ( 400 IU ) vitamin D(3 ) plus 1000 mg calcium/day , or ( 4 ) combined vitamins K(1 ) and D(3 ) plus calcium . Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist , markers of bone turnover , and vitamin status . Supplementation effects were tested using multivariate general linear modeling , with full adjustment for baseline and potential confounding variables . RESULTS Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups . However , women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius . Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years , serum vitamin K(1 ) increased by 157 % ( p percentage of undercarboxylated osteocalcin ( % GluOC ) decreased by 51 % ( p serum 25-hydroxyvitamin D [ 25(OH)D ] increased by 17 % ( p PTH decreased by 11 % ( p = 0.049 ) . CONCLUSIONS These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K(1 ) together with supplements of calcium plus moderate vitamin D(3 ) to enhance BMC at the ultradistal radius , a site consisting of principally trabecular bone . The substantial increase in gamma-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation", "UNLABELLED In this 2-year r and omized controlled study of 167 men > 50 years of age , supplementation with calcium-vitamin D3-fortified milk providing an additional 1000 mg of calcium and 800 IU of vitamin D3 per day was effective for suppressing PTH and stopping or slowing bone loss at several clinical ly important skeletal sites at risk for fracture . INTRODUCTION Low dietary calcium and inadequate vitamin D stores have long been implicated in age-related bone loss and osteoporosis . The aim of this study was to assess the effects of calcium and vitamin D3 fortified milk on BMD in community living men > 50 years of age . MATERIAL S AND METHODS This was a 2-year r and omized controlled study in which 167 men ( mean age + /- SD , 61.9 + /- 7.7 years ) were assigned to receive either 400 ml/day of reduced fat ( approximately 1 % ) ultra-high temperature ( UHT ) milk containing 1000 mg of calcium plus 800 IU of vitamin D3 or to a control group receiving no additional milk . Primary endpoints were changes in BMD , serum 25(OH)D , and PTH . RESULTS One hundred forty-nine men completed the study . Baseline characteristics between the groups were not different ; mean dietary calcium and serum 25(OH)D levels were 941 + /- 387 mg/day and 77 + /- 23 nM , respectively . After 2 years , the mean percent change in BMD was 0.9 - 1.6 % less in the milk supplementation compared with control group at the femoral neck , total hip , and ultradistal radius ( range , p lumbar spine BMD in the milk supplementation group after 12 and 18 months ( 0.8 - 1.0 % , p Serum 25(OH)D increased and PTH decreased in the milk supplementation relative to control group after the first year ( 31 % and -18 % , respectively ; both p Body weight remained unchanged in both groups at the completion of the study . CONCLUSIONS Supplementing the diet of men > 50 years of age with reduced-fat calcium- and vitamin D3-enriched milk may represent a simple , nutritionally sound and cost-effective strategy to reduce age-related bone loss at several skeletal sites at risk for fracture in the elderly", "UNLABELLED Bone metabolism follows a seasonal pattern with high bone turnover and bone loss during the winter . In a r and omized , open-label 2-year sequential follow-up study of 55 healthy adults , we found that supplementation with oral vitamin D3 and calcium during winter abolished seasonal changes in calciotropic hormones and markers of bone turnover and led to an increase in BMD . Supplementation with oral vitamin D3 and calcium during the winter months seems to counteract the effects of seasonal changes in vitamin D and thus may be beneficial as a primary prevention strategy for age-related bone loss . INTRODUCTION Bone metabolism follows a seasonal pattern characterized by high bone turnover and bone loss during winter . We investigated whether wintertime supplementation with oral vitamin D3 and calcium had beneficial effects on the circannual changes in bone turnover and bone mass . MATERIAL S AND METHODS This prospect i ve study comprised an initial observation period of 12 months ( \" year 1 \" ) , followed by an intervention during parts of year 2 . Fifty-five healthy subjects living in southwestern Germany ( latitude , 49.5 degrees N ) were r and omized into two groups : 30 subjects were assigned to the treatment group and received oral cholecalciferol ( 500 IU/day ) and calcium ( 500 mg/day ) during the winter months of year 2 ( October-April ) , while 25 subjects assigned to the control group obtained no supplements . Primary endpoints were changes in calciotropic hormones [ serum 25(OH)D , 1,25(OH)2D , and parathyroid hormone ] , markers of bone formation ( serum bone-specific alkaline phosphatase ) and of bone resorption ( urinary pyridinoline and deoxypyridinoline ) , and changes in lumbar spine and femoral neck BMD . RESULTS Forty-three subjects completed the study . During year 1 , calciotropic hormones , markers of bone turnover , and BMD varied by season in both groups . During the winter months of year 1 , bone turnover was significantly accelerated , and lumbar spine and femoral BMD declined by 0.3 - 0.9 % . In year 2 , seasonal changes in calciotropic hormones and markers of bone turnover were either reversed or abolished in the intervention group while unchanged in the control cohort . In the subjects receiving oral vitamin D3 and calcium , lumbar and femoral BMD increased significantly ( lumbar spine : + 0.8 % , p = 0.04 versus year 1 ; femoral neck : + 0.1 % , p = 0.05 versus year 1 ) , whereas controls continued to lose bone ( intervention group versus control group : lumbar spine , p = 0.03 ; femoral neck , p = 0.05 ) . CONCLUSIONS Supplementation with oral vitamin D3 and calcium during winter prevents seasonal changes in bone turnover and bone loss in healthy adults . It seems conceivable that annually recurring cycles of low vitamin D and mild secondary hyperparathyroidism during the winter months contributes , at least in part and over many years , to age-related bone loss . Supplementation with low-dose oral vitamin D3 and calcium during winter may be an efficient and inexpensive strategy for the primary prevention of bone loss in northern latitudes", "BACKGROUND Care of elderly patients after hip fracture is not well established . METHODS We enrolled 173 patients with acute hip fracture who were 65 years or older ( 79.2 % women ; mean age , 84 years ; 77.4 % living at home ) . Using a factorial design , we r and omly allocated patients to extended physiotherapy ( PT ) ( supervised 60 min/d during acute care plus an unsupervised home program ) vs st and ard PT ( supervised 30 min/d during acute care plus no home program ; single-blinded ) , and to cholecalciferol therapy , 2000 vs 800 IU/d ( double-blinded ) . Primary outcome was rate of falls ; secondary outcome was rate of hospital readmissions during the 12-month follow-up . All analyses included 173 individuals and used multivariate Poisson regression analyses . RESULTS At baseline , 50.9 % of participants had 25-hydroxyvitamin D levels of less than 12 ng/mL and 97.7 % of less than 30 ng/mL. We documented 212 falls and 74 hospital readmissions . Because this was a factorial design trial , all analyses tested the main effect of each treatment while controlling for the other in 173 participants . Extended vs st and ard PT reduced the rate of falls by 25 % ( 95 % confidence interval [ CI ] , -44 % to -1 % ) . Cholecalciferol treatment , 2000 vs 800 IU/d , did not reduce falls ( 28 % ; 95 % CI , -4 % to 68 % ) , but reduced the rate of hospital readmissions by 39 % ( 95 % CI , -62 % to -1 % ) . CONCLUSIONS Extended PT was successful in reducing falls but not hospital readmissions , whereas cholecalciferol treatment , 2000 IU/d , was successful in reducing hospital readmission but not falls . Thus , the 2 strategies may be useful together because they address 2 different and important complications after hip fracture", "A r and omized double-blind controlled trial of the effect of vitamin D supplementation on the abilities of elderly hospital patients to carry out basic activities of daily life is described . Those patients included in the trial had plasma 25-hydroxyvitamin D concentrations which were low or low normal as judged by the normal range in young adults . After 2 to 9 months on the trial there was no significant difference in the performance of the control and treatment groups", "In this prospect i ve study , the authors determined intrinsic risk factors for falls and recurrent falls and constructed a risk profile that indicated the relative contribution of each risk factor and also estimated the probabilities of falls and recurrent falls . In 1992 , over a 28-week period , falls were recorded among 354 elderly subjects aged 70 years or over who were living in homes or apartments for the elderly in Amsterdam and the vicinity . During the study period , 251 falls were reported by 126 subjects ( 36 % ) , and recurrent falls ( > or = 2 falls ) were reported by 57 subjects ( 16 % ) . Associations of falls and recurrent falls with potential risk factors were identified in logistic regression models . Mobility impairment regarding one or more of the tested items ( i.e. , impairment of balance , leg-extension strength , and gait ) was associated with falls ( adjusted odds ratio ( OR ) = 2.6 ) and was strongly associated with recurrent falls ( OR = 5.0 ) . Dizziness upon st and ing was associated with falls ( OR = 2.1 ) and recurrent falls ( OR = 2.1 ) . However , several risk factors were associated with recurrent falls only : history of stroke ( OR = 3.4 ) , poor mental state ( OR = 2.4 ) , and postural hypotension ( OR = 2.0 ) . The authors constructed a risk profile for recurrent falls that included the five risk factors mentioned above . Inclusion of all risk factors in the profile implied an 84 % probability of recurrent falls over a period of 28 weeks , compared with 3 % when no risk factor was present . The probability of recurrent falls ranged only from 11 % to 29 % when predicted by number of falls occurring in the previous year . Physical activity , use of high-risk medication , and the use of vitamin D3 , which was r and omly allocated to the participants , were not strongly related to either falls or recurrent falls . In conclusion , a large range of probabilities of falls , especially of recurrent falls , was estimated by the risk profiles , in which mobility impairment was the major risk factor . Recurrent fallers may therefore be especially amenable to prevention based on mobility improvement", "Dietary supplements that prevent bone loss at the hip and that can be applied safely in the elderly are likely to reduce hip fractures . A daily dietary supplement of 750 mg calcium or 15 microg 25OH vitamin D3 on bone loss at the hip and other sites , bone turnover and calcium-regulating hormones were studied over 4 yr in elderly volunteers using a r and omized , double-blind , placebo-controlled trial . Bone mineral density ( BMD ) was measured by dual x-ray absorptiometry and bone structure by radiographs . Calcium biochemistry and bone turnover markers were measured in blood and urine . The 316 women entering the trial had a mean age of 73.7 yr and the 122 men of 75.9 yr . Baseline median calcium intake was 546 mg/day , and median serum 25OH vitamin D3 was 59 nmol/L. On placebo , loss of BMD at total hip was 2 % and femoral medulla expansion was 3 % over 4 yr . Calcium reduced bone loss , secondary hyperparathyroidism , and bone turnover . 25OH vitamin D3 was intermediate between placebo and calcium . Fracture rates and drop-out rates were similar among groups , and there were no serious adverse events with either supplement . A calcium supplement of 750 mg/day prevents loss of BMD , reduces femoral medullary expansion , secondary hyperparathyroidism , and high bone turnover . A supplement of 15 microg/day 25OH vitamin D3 is less effective , and because its effects are seen only at low calcium intakes , suggests that its beneficial effect is to reverse calcium insufficiency", "Background and aims : Insufficient vitamin D status , commonly found in older people , has been associated with muscle weakness which , in old age , impairs mobility and is a risk factor for falling . In a r and omized , double-blind placebo-controlled trial , we tested the hypothesis that vitamin D + calcium supplementation improves muscle strength and mobility , compared with calcium mono-therapy in vitamin D-insufficient female geriatric patients . Methods : Seventy female geriatric patients > 65 years of age with serum 25-hydroxyvitamin D3 ( 25OHD ) concentrations between 20 and 50 nmol/L , visiting an outpatient geriatric department , were included . Participants received either cholecalciferol 400 IU/day + calcium 500 mg/day ( D/Cal group ) or a placebo + calcium 500 mg/day ( Plac/Cal group ) for 6 months . At baseline and 6 months , muscle strength , power and functional mobility were tested . Results : At baseline , 25OHD was significantly ( p with knee extension strength ( r=0.42 ) , h and grip strength ( r=0.28 ) , leg extension power ( r=0.34 ) , Timed Get Up and Go ( r=−0.31 ) and Modified Cooper test ( r=0.44 ) . At 6 months , a significant difference in 25OHD ( 77.2 vs 41.6 nmol/L , p and 1,25OHD was found between the two groups . Significantly improving vitamin D status in the D/Cal group compared with the Plac/Cal group did not result in a significant difference in strength or functional mobility between the two groups . Conclusions : Daily 400IU vitamin D + 500 mg calcium supplementation is not enough to significantly improve strength or mobility in vitamin D-insufficient female geriatric patients", "The purpose of the study was to determine the effect of vitamin D supplementation on bone turnover and bone loss in elderly women . Three hundred forty-eight women , ages 70 yr and older , were r and omized to receive 400 IU vitamin D3 per day ( n = 177 ) or placebo ( n = 171 ) , double-blind , for a period of 2 yr . Main outcome measures were bone mineral density of both hips ( femoral neck and trochanter ) and the distal radius , as well as biochemical markers of bone turnover . The effect of vitamin D supplementation was expressed as the difference in mean ( percentage ) change between the placebo group and the vitamin D group . The measurements were repeated in 283 women after 1 yr and in 248 women after 2 yr . Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D ( 250HD ) ( + 35 nmol/L ) and 1,25-dehydroxyvitamin D [ 1,25-(OH)2D ] ( + 7.0 pmol/L ) levels and urinary calcium/creatinine ratios ( + 0.5 % ) and significantly decreased PTH(1 - 84 ) secretion ( -0.74 pmol/L ) after 1 yr . No effect was found for the parameters of bone turnover . The effect on the bone mineral density of the left femoral neck was + 1.8 % in the first yr , + 0.2 % in the second yr , and + 1.9 % during the whole period ( 95 % confidence interval 0.4 , 3.4 % ) . At the right femoral neck the effects were + 1.5 % , + 1.1 % , and + 2.6 % ( confidence interval 1.1 , 4.0 % ) , respectively . No effect was found at the femoral trochanter and the distal radius . Supplementation with 400 IU vitamin D3 daily in elderly women slightly decreases PTH secretion and increases bone mineral density at the femoral neck", "Abstract : Vitamin D status is known to be an important determinant of bone mineral density ( BMD ) . There is a significant seasonal variation in serum vitamin D , and some studies have reported an associated seasonal variation in BMD . The present study was devised to investigate whether a seasonal variation in BMD could be detected in healthy normal subjects , along with associated variations in serum parathyroid hormone ( PTH ) , intestinal calcium absorption and biochemical markers of bone turnover . A second aim was to investigate whether , if such variations were identified , they could be suppressed by vitamin D supplementation . The subjects were 70 healthy female volunteers ( mean age 47.2 years , range 24–70 years ) recruited into a double-masked crossover study and followed over 2 years . During the first year 35 subjects received a daily oral supplement containing 800 IU ( 20 mg ) cholecalciferol ( group 1 ) and 35 subjects received a placebo preparation ( group 2 ) . During the second year the treatment each group received was reversed . Lumbar spine ( L1–L4 ) , left proximal femur and total body BMD were measured by DXA at 3-month intervals . Serum 25-hydroxyvitamin D ( 25-OHD ) , serum PTH , bone markers ( bone-specific ALP ( BSAP ) and urinary crosslinks ( DYPD/creatinine ) ) and calcium absorption were also measured at each visit . Cholecalciferol treatment increased serum 25-OHD by 25.4 nmol/l ( p serum PTH of 6.6 ng/l ( p = 0.011 ) was seen in subjects in the lowest quartile of baseline serum 25-OHD . The treatment had no significant effect on spine , femur or total body BMD , calcium absorption or bone markers . When Fourier analysis was used to analyze the data for seasonal effect ( defined as twice the amplitude of the 1-year period variation ) a highly significant effect for 25-OHD of 18 nmol/l ( p for BMD , PTH , calcium absorption or bone markers . The analysis set a 95 % confidence limit to the seasonal effect of less than 0.6 % for spine , total hip and total body BMD . It was concluded that in the population of healthy women studied there was no evidence of seasonal variation in spine , femur or total body BMD , serum PTH , calcium absorption or bone markers . Vitamin D supplementation was found to have no effect on BMD ", "A double-blind controlled study was performed in 60 patients with symptomatic osteoporosis with at least one vertebral crush fracture , comparing the effect of n and rolone decanoate , 1 alpha-hydroxyvitamin D3 and intermittent calcium infusions . Thirty-four out of 60 patients completed the 2 year observation period . N and rolone decanoate statistically significantly increased the bone mineral content at the radius , reduced the endosteal bone loss at the metacarpals and statistically significantly reduced urinary calcium and hydroxyproline excretion . Calcium infusions and 1 alpha-hydroxyvitamin D3 inhibited further loss of bone mineral content , but endosteal bone loss continued . In the second year fracture rate was reduced in the n and rolone decanoate groups compared to the two other groups . We conclude that n and rolone decanoate is an active drug for increasing bone mineral content and reducing endosteal bone loss , while 1 alpha-hydroxyvitamin D3 and calcium infusions only stop further bone mineral loss at the radius but do not inhibit endosteal bone loss as measured at the metacarpals and that single photon absorptiometry and radiography are complementary in interpreting cortical bone mineral changes", "PURPOSE Oral bone and tooth loss are correlated with bone loss at nonoral sites . Calcium and vitamin D supplementation slow the rate of bone loss from various skeletal sites , but it is not known if intake of these nutrients affects oral bone and , in turn , tooth retention . SUBJECTS AND METHODS Tooth loss was examined in 145 healthy subjects aged 65 years and older who completed a 3-year , r and omized , placebo-controlled trial of the effect of calcium and vitamin D supplementation on bone loss from the hip , as well as a 2-year follow-up study after discontinuation of study supplements . Teeth were counted at 18 months and 5 years . A comprehensive oral examination at 5 years included assessment of caries , oral hygiene , and periodontal disease . The odds ratio ( OR ) and 95 % confidence interval ( CI ) of tooth loss were estimated by stepwise multivariate logistic regression . Initial age ( mean + /- SD ) of subjects was 71 + /- 5 years , and the number of teeth remaining was 22 + /- 7 . RESULTS During the r and omized trial , 11 of the 82 subjects ( 13 % ) taking supplements and 17 of the 63 subjects ( 27 % ) taking placebo lost one or more teeth ( OR = 0.4 ; 95 % CI : 0.2 to 0.9 ) . During the 2-year follow-up period , 31 of the 77 subjects ( 40 % ) with total calcium intake of at least 1000 mg per day lost one or more teeth compared with 40 of the 68 subjects ( 59 % ) who consumed less ( OR = 0.5 ; 95 % CI : 0.2 to 0.9 ) . CONCLUSION These findings suggest that intake levels of calcium and vitamin D aim ed at preventing osteoporosis have a beneficial effect on tooth retention", "Abstract The effect of the combined administration of vitamin D3 and vitamin K2 on bone mineral density ( BMD ) of the lumbar spine was examined in postmenopausal women with osteoporosis . Ninety-two osteoporotic women who were more than 5 years after menopause , aged 55–81 years , were r and omly divided into four administration groups : vitamin D3 ( 1α hydroxyvitamin D3 , 0.75 μg/day ) ( D group ; n = 29 ) , vitamin K2 ( menatetrenone , 45 mg/day ) ( K group ; n = 22 ) , vitamin D3 plus vitamin K2 ( DK group , n = 21 ) , and calcium ( calcium lactate , 2 g/day ) ( C group ; n = 20 ) . BMD of the lumbar spine ( L2–L4 ) was measured by dual energy X-ray absorptiometry at 0 , 1 , and 2 years after the treatment started . There were no significant differences in age , body mass index , years since menopause , and initial BMD among the four groups . One-way analysis of variance ( ANOVA ) with repeated measurements showed a significant decrease in BMD in the C group ( P increase in BMD in the D and K groups compared with that in the C group ( P in BMD in the DK group compared with that in the C , D , and K groups ( P of vitamin D3 and vitamin K2 , compared with calcium administration , appears to be useful in increasing the BMD of the lumbar spine in postmenopausal women with osteoporosis", "OBJECTIVE This article presents the results of an evaluation of the clinical and laboratory safety of a 1-year course of treatment with a combination calcium and vitamin D tablet in ambulatory women aged > 65 years with vitamin D insufficiency . METHODS In a multicenter , r and omized , double-blind , placebo-controlled study conducted in France , women with a 25-hydroxyvitamin D level were r and omized to receive either a combination tablet containing calcium carbonate 500 mg and vitamin D3 400 IU taken twice daily or a matching placebo tablet for 1 year . A complete clinical examination was performed at baseline and at 3 , 6 , 9 , and 12 months of treatment ; blood and urine sample s were collected for laboratory analyses at the same time points . Safety was monitored based on adverse events recorded during the treatment period and on the results of laboratory tests , including measurement of creatinine and uric acid levels . RESULTS The study included 192 women ( mean [ SD ] age , 74.6 [ 6.9 ] years ; mean weight , 64.0 [ 12.5 ] kg ) , 95 in the calcium + vitamin D group and 97 in the placebo group . Fifty women ( 21/95 [ 22.1 % ] calcium + vitamin D , 29/96 [ 30.2 % ] placebo ) were prematurely withdrawn from the study for various reasons , with no difference in withdrawals between groups . Treatment-related adverse events were reported in 21 ( 22.1 % ) and 23 ( 24.0 % ) women in the respective treatment groups . These events consisted mainly of metabolic disorders ( 9 [ 9.5 % ] and 10 [ 10.4 % ] , respectively ) , particularly hypercalcemia ( 6 [ 6.3 % ] and 8 [ 8.3 % ] ) and gastrointestinal disorders ( 9 [ 9.5 % ] and 8 [ 8.3 % ] ) . No major complications directly related to calcium and vitamin D supplementation occurred during the course of treatment . Although renal function was not altered , the group who received calcium + vitamin D had significantly elevated concentrations of serum uric acid compared with those who received placebo ( 52.3 % vs 37.2 % ; P = 0.046 ) but not urinary uric acid . CONCLUSIONS In these ambulatory elderly women with vitamin D deficiency , supplementation with calcium + vitamin D appeared to be well tolerated over 1 year of treatment . No significant effects on creatinine clearance were observed . However , the proportion of women with elevated serum uric acid concentrations was significantly greater in those who received calcium + vitamin D compared with those who received placebo ", "BACKGROUND The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal . METHODS We recruited 36,282 postmenopausal women , 50 to 79 years of age , who were already enrolled in a Women 's Health Initiative ( WHI ) clinical trial . We r and omly assigned participants to receive 1000 mg of elemental [ corrected ] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo . Fractures were ascertained for an average follow-up period of 7.0 years . Bone density was measured at three WHI centers . RESULTS Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group ( P calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture ( 95 percent confidence interval , 0.72 to 1.08 ) , 0.90 for clinical spine fracture ( 0.74 to 1.10 ) , and 0.96 for total fractures ( 0.91 to 1.02 ) . The risk of renal calculi increased with calcium plus vitamin D ( hazard ratio , 1.17 ; 95 percent confidence interval , 1.02 to 1.34 ) . Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 ( 95 percent confidence interval , 0.52 to 0.97 ) . Effects did not vary significantly according to prer and omization serum vitamin D levels . CONCLUSIONS Among healthy postmenopausal women , calcium with vitamin D supplementation result ed in a small but significant improvement in hip bone density , did not significantly reduce hip fracture , and increased the risk of kidney stones . ( Clinical Trials.gov number , NCT00000611 . )", "Abstract . To assess the efficacy and acceptability of vitamin D-fortified liquid milk in the management of hypovitaminosis D we carried out a double-blind , r and omized , controlled trial on 51 community-based , elderly subjects with serum 25 hydroxyvitamin D ( 25OHD ) levels of less than 12.9 ng/ml ( normal range 10–80 ng/ml ) . Each subject had a dietary assessment , mental test score , outdoor score , serum 25 hydroxyvitamin D level , and a general biochemical screening at baseline in April 1993 which was repeated in September 1993 , April 1994 , and September 1994 . All subjects received 500 ml of milk per day , delivered to their homes in specially manufactured , blank , tetrapak cartons , from June 1993 to June 1994 : 23 subjects received unfortified milk ( control group ) and 28 subjects received fortified milk ( active group ) . Our results showed a baseline mean 25OHD level in the active group of 9.6 ( range mean 25OHD level in the active group had risen significantly from its baseline to 18.5 ( range 9.6–26.7 ) ng/ml ( P ) . Serum calcium levels in the active group also showed a significant rise over the 1-year period ( P vitamin D-fortified liquid milk is a safe , effective , and acceptable method of administering vitamin D to the elderly , community-based population", "Abstract : We undertook a double-masked , r and omized , placebo-controlled trial to evaluate the effect of a calcium and vitamin D supplement and a calcium supplement plus multivitamins on bone loss at the hip , spine and forearm . The study was performed in 240 healthy women , 58–67 years of age . Duration of treatment was 2 years . Bone mineral density ( BMD ) was measured at the lumbar spine , hip and forearm . A dietary question naire was administered twice during the study and revealed a fairly good calcium and vitamin D intake ( 919 mg calcium/day ; 3.8 mg vitamin D/day ) . An increase in lumbar spine BMD of 1.6 % was observed in the treatment group after 2 years ( p50.002 ) . In the placebo group no significant changes were observed during the 2 years . Lumbar spine BMD was significantly higher in the treatment group at both 1 ( p50.01 ) and 2 years ( p50.05 ) compared with the placebo group . Though not significant , the same trend was seen at the hip . No significant changes from baseline values were observed at the distal forearm in either the treatment or the placebo group . In conclusion , we found a significant increase in urinary calcium excretion in the treatment group compared with the placebo group . Together with significant changes in serum calcium and serum parathyroid hormone , this indicates that a long-term calcium and vitamin supplement of 1 g elementary calcium ( calcium carbonate ) and 14 mg vitamin D3 increases intestinal calcium absorption . A positive effect on BMD was demonstrated , even in a group of early postmenopausal age , with a fairly good initial calcium and vitamin D status", "Daily vitamin D in addition to calcium supplementation reduces falls and fractures in older women . However , poor adherence to therapy is a common clinical problem . To examine the effects of supervised oral 3-monthly vitamin D therapy on falls , muscle strength , and mobility , we conducted a 9-month r and omized , double-blind , placebo-controlled trial in 686 community-dwelling ambulant women aged over 70 years . Participants received either oral cholecalciferol 150,000 IU every 3 months ( n = 353 ) or an identical placebo ( n = 333 ) . All participants were advised to increase dietary calcium intake . Falls data were collected 3-monthly . At baseline , 3 , 6 , and 9 months , muscle strength was measured by a h and held dynamometer and mobility by the Timed Up and Go ( TUG ) test . Serum 25 hydroxyvitamin D ( 25OHD ) was measured in a subgroup of 40 subjects . Mean age at baseline was 76.7 ± 4.1 years . The average serum 25OHD value at baseline was 65.8 ± 22.7 nmol/L. By 3 , 6 , and 9 months after supplementation , 25OHD levels of the vitamin D group were approximately 15 nmol/L higher than the placebo group . Calcium intake did not change significantly between baseline ( 864 ± 412 mg/day ) and 9 months ( 855 ± 357 mg/day ) . Faller rates in the two groups did not differ : vitamin D group , 102 of 353 ( 29 % ) ; placebo group , 89 of 333 ( 27 % ) . At 9 months , compared to placebo or baseline , muscle strength , and TUG were not altered by vitamin D. In conclusion , oral cholecalciferol 150,000 IU therapy administered 3-monthly had neither beneficial nor adverse effects on falls or physical function . These data together with previous findings confirm that intermittent large doses of vitamin D are ineffective or have a deleterious effect on falls . Thus despite adherence issues with daily vitamin D replacement , an intermittent , high-dose vitamin D regimen can not be supported as a strategy to reduce falls and fractures", "OBJECTIVES To determine whether vitamin D supplementation reduces the risk of fracture or falls in elderly people in care home accommodation . DESIGN A r and omised controlled trial of cluster design . SETTING AND SUBJECTS 223 Residential units ( mainly identical 30-bedded units ) , within 118 homes for elderly people throughout Britain , with 3,717 participating residents ( 76 % women , average age 85 years ) . The units provided mainly or entirely residential care ( 35 % of residents ) , nursing care ( 42 % ) or care for elderly mentally infirm ( EMI ) residents ( 23 % ) . METHODS Participants were r and omly allocated by residential unit ( cluster design ) to a treated group offered ergocalciferol 2.5 mg every 3 months ( equivalent to a daily dose of 1,100 IU ) , or to a control group . Fractures were reported by staff and confirmed in hospital , and routinely collected data on reported falls were obtained . RESULTS After median follow-up of 10 months ( interquartile range 7 - 14 months ) , 64 ( 3.6 % ) of 1,762 vitamin D-treated residents and 51 ( 2.6 % ) of 1,955 controls had one or more non-vertebral fractures , and 24 ( 1.3 % ) and 20 ( 1.0 % ) , respectively , had a hip fracture . The proportion reporting at least one fall was 44 % in vitamin D-treated and 43 % in control residents . The differences between the vitamin D and control groups were not statistically significant . The incidence of all non-vertebral fractures in the care homes ( 3.2 % per year ) and of hip fractures ( 1.1 % per year ) was low , similar to rates in elderly people in sheltered accommodation , and the pre-treatment serum 25-hydroxy vitamin D concentration was high [ median 47 nmol/l , measured in a 1 % ( n = 18 ) sample ] . CONCLUSIONS We found no evidence that vitamin D prevents fractures or falls in elderly people in care home accommodation", "OBJECTIVES We investigated the incidence of new non-vertebral fractures during HRT or low-dose vitamin ( Vit ) D3 supplementation in a 5-year prospect i ve trial . METHODS A total of 464 early postmenopausal women , ( a subgroup of the Kuopio Osteoporosis Study , n = 13100 ) were r and omized to four groups : ( 1 ) HRT , a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate ; ( 2 ) Vit D ( 300 IU/day and 100 IU/day during the fifth year ) ; ( 3 ) HRT + Vit D ; and ( 4 ) placebo . Lumbar ( L2 - 4 ) and femoral neck bone mineral densities ( BMD ) were determined by dual X-ray absorptiometry ( DXA ) at baseline , after 2.5 and 5 years of treatment . All new symptomatic non-vertebral , radiographically defined fractures were recorded . RESULTS Altogether , 368 women ( 79 % ) completed the 5 year treatment . In all , 32 women had 39 non-vertebral fractures during a mean of 4.3 year follow-up ( HRT 4 , Vit D 10 , HRT + Vit D 8 and placebo 17 ) . The reduction in the incidence of new non-verterbral fractures was significant in women with HRT alone ( P = 0.032 ) when adjusted by baseline BMD and previous fractures ; observed also with the intention-to-treat principle ( P = 0.048 ) . When the HRT groups were pooled , HRT showed a significantly lower incidence of new non-vertebral fractures ( P = 0.042 ) than women receiving placebo and also after adjusting as above ( P = 0.016 ) ; both in valid-case and in the intention-to-treat analysis . In the Vit D group , the fracture incidence was non-significantly decreased ( P = 0.229 ) in comparison with the placebo group . The estimated risk of new non-vertebral fractures among women treated with HRT alone was 0.29 ( 95 % CI , 0.10 - 0.90 ) and with Vit D 0.47 ( 95 % CI , 0.20 - 1.14 ) and with HRT + Vit D 0.44 ( 95 % CI , 0.17 - 1.15 ) , in comparison with the placebo group ( adjusted by femoral BMD and previous fractures ) . CONCLUSIONS This study is the first prospect i ve trial confirming the beneficial effect of HRT on prevention of peripheral fractures in non-osteoporotic postmenopausal women . The effect of low-dose Vit D remains to be proved", "Twenty-eight women with postmenopausal osteoporosis were studied in a double-blind trial aim ed to compare the effects of a one-year treatment with 1,25-dihydroxyvitamin D3 ( 1,25(OH)2D3 ) , estradiol valerate ( E2 ) and placebo . Patients were divided into 4 groups : group 1 was given 1,25(OH)2D3 alone , group 2 was given E2 alone , group 3 was given 1,25(OH)2D3 + E2 , group 4 received a placebo . The evaluation of the effects of the treatments included clinical examination of patients , the measurement of a number of biochemical parameters , such as plasma and urinary calcium and phosphate , urinary hydroxyproline , serum alkaline phosphatase , the measurement of intestinal calcium absorption and bone mineral content ( BMC ) and a histomorphometric study of bone biopsies from the iliac crest . The best clinical results were obtained in the patients who were given 1,25(OH)2D3 alone ; appreciable results were also noticed in the patients who were given E2 alone or in combination with 1,25(OH)2D3 , while patients in the placebo group worsened . BMC decreased in the placebo group and increased , although non significantly , in the patients treated with 1,25(OH)2D3 or E2 or both . The histomorphometric study showed a significant increase in the mean trabecular diameter in patients treated with 1,25(OH)2D3 alone or in combination with E2 . Changes in the volume density of trabecular bone paralleled those in BMC . The results of the trial indicate that 1,25(OH)2D3 is an effective therapeutic agent in postmenopausal osteoporosis", "OBJECTIVES To determine whether relative vitamin D deficiency during the winter months contributes to age-related bone loss and whether rates of change in hard- and soft-tissue mass vary during the year . DESIGN Double-blind , placebo-controlled , 1-year trial in 249 women in which equal numbers of women were r and omized to either placebo or 400 IU of vitamin D daily . All women received 377 mg/d of supplemental calcium largely as calcium citrate malate . PATIENTS Healthy , ambulatory postmenopausal women with usual intakes of vitamin D of 100 IU/d . MEASUREMENTS Duplicate spine and whole-body scans were done by dual energy x-ray absorptiometry at 6-month intervals that were timed to periods when 25-hydroxyvitamin D levels were highest and lowest . Period 1 was June-July to December-January and period 2 was December-January to the next June-July . Serum parathyroid hormone and plasma 25-hydroxyvitamin D levels were measured during periods 1 and 2 . MAIN RESULTS In the placebo group , spinal bone mineral density increased in period 1 , decreased in period 2 , and sustained no net change . Women treated with vitamin D had a similar spinal increase in period 1 ( 1.46 % compared with 1.40 % in placebo ) , less loss in period 2 ( -0.54 % compared with -1.22 % , CI for the difference , 0.05 % to 1.31 % , P = 0.032 ) and a significant overall benefit ( 0.85 % compared with 0.15 % , CI for the difference , 0.03 % to 1.37 % , P = 0.04 ) . In period 2 , 25-hydroxyvitamin D levels were lower and parathyroid hormone levels were higher in the placebo than in the vitamin D group . Whole-body lean and fat tissue and bone mineral density varied during the year but did not change overall . CONCLUSIONS At latitude 42 degrees , healthy postmenopausal women with vitamin D intakes of 100 IU daily can significantly reduce late wintertime bone loss and improve net bone density of the spine over one year by increasing their intake of vitamin D to 500 IU daily . A long-term benefit of preventing vitamin D insufficiency in the winter seems likely although it remains to be shown . Observed changes in bone as well as in fat and lean tissue appear to be related to season", "Background and aims : Supplementation of postmenopausal women with calcium alone or calcium-vitamin D association was suggested to have positive effects on bone turnover and bone density , as well as to lower fracture incidence . The beneficial effect appears to be mediated by a reduction in parathyroid hormone secretion . Our aim was to compare the respective efficacy of calcium and calcium-vitamin D supplements in reducing serum parathyroid hormone levels in postmenopausal women with prevalent low 25(OH)vitamin D levels . Methods : One hundred consecutive ambulatory postmenopausal women with serum 25(OH)vitamin D levels below 18 ng/mL were included in a r and omized , prospect i ve , open label study . For a duration of 90 days , the women were r and omly assigned to a daily supplementation of either one tablet of calcium gluconolactate and carbonate ( 500 mg calcium ) , or one powder-pack of an association of calcium carbonate ( 500 mg calcium ) , citric acid ( 2.175 gr ) and cholecalciferol ( 200 IU ) . Changes observed during the 90 days of the study in circulating PTH levels were the primary endpoint , while changes in serum 25(OH)D levels were assessed as secondary endpoint . Results : A significant difference was observed between the calcium-vitamin D ( CaD ) and the calcium ( Ca ) only groups for changes occurring during the 90 days of the study in PTH ( −14.5±40 % and + 2.5±46 % ) ( p=0.009 ) and 25(OH)D ( + 67±77 % and + 18±55 % ) ( p levels . PTH changes between baseline and day 90 were significant in the CaD group , but not in the Ca group . The odds ratio for a patient in group Ca to experience an absolute ( in circulating 25(OH)vitamin D levels , compared to a group CaD patient was statistically increased ( OR : 3.22 , 95 % CI : 1.33–7.80 ) . Conclusions : Our results support the recommendation of supplementing postmenopausal women with low circulating levels of 25(OH)vitamin D with a combination of calcium and vitamin D , rather than with calcium alone", "OBJECTIVES To determine whether vitamin D supplementation can reduce the incidence of falls and fractures in older people in residential care who are not classically vitamin D deficient . DESIGN R and omized , placebo-controlled double-blind , trial of 2 years ' duration . SETTING Multicenter study in 60 hostels ( assisted living facilities ) and 89 nursing homes across Australia . PARTICIPANTS Six hundred twenty-five residents ( mean age 83.4 ) with serum 25-hydroxyvitamin D levels between 25 and 90 nmol/L. INTERVENTION Vitamin D supplementation ( ergocalciferol , initially 10,000 IU given once weekly and then 1,000 IU daily ) or placebo for 2 years . All subjects received 600 mg of elemental calcium daily as calcium carbonate . MEASUREMENTS Falls and fractures recorded prospect ively in study diaries by care staff . RESULTS The vitamin D and placebo groups had similar baseline characteristics . In intention-to-treat analysis , the incident rate ratio for falling was 0.73 ( 95 % confidence interval (CI)=0.57 - 0.95 ) . The odds ratio for ever falling was 0.82 ( 95 % CI=0.59 - 1.12 ) and for ever fracturing was 0.69 ( 95 % CI=0.40 - 1.18 ) . An a priori subgroup analysis of subjects who took at least half the prescribed capsules ( n=540 ) , demonstrated an incident rate ratio for falls of 0.63 ( 95 % CI=0.48 - 0.82 ) , an odds ratio ( OR ) for ever falling of 0.70 ( 95 % CI=0.50 - 0.99 ) , and an OR for ever fracturing of 0.68 ( 95 % CI=0.38 - 1.22 ) . CONCLUSION Older people in residential care can reduce their incidence of falls if they take a vitamin D supplement for 2 years even if they are not initially classically vitamin D deficient", "Introduction The objectives were:(1 ) to vali date a quantitative balance assessment method for fall risk prediction ; ( 2 ) to investigate whether the effect of vitamin D and calcium on the risk of falling is mediated through postural or dynamic balance , as assessed by this method . Material s and methods A secondary analysis of a double blind r and omized controlled trial was employed , which included 64 institutionalized elderly women with complete balance assessment ( age range : 65–97 ; mean 25–hydroxyvitamin D levels : 16.4 ng/ml ( SD ±9.9 ) . Participants received 1,200 mg calcium plus 800 IU cholecalciferol ( n=33 ) or 1,200 mg calcium ( n=31 ) per day over a 3-month treatment period . Using an electronic device attached to the lower back of the participant , balance was assessed as the degree of trunk angular displacement and angular velocity during a postural task ( st and ing on two legs , eyes open , for 20 s ) and a dynamic task ( get up from a st and ard height chair with arm rests , sit down and then st and up again and remain st and ing ) . Results It was found that both postural and dynamic balance independently and significantly predicted the rate of falling within the 3-month follow-up . Vitamin D plus calcium reduced the rate of falls by 60 % [ relative risk (RR)=0.40 ; 95 % CI : 0.17 , 0.94 ] if compared with calcium alone . Once postural and dynamic balance were added to the regression analysis , they both attenuated the effect of vitamin D plus calcium on the rate of falls . For postural balance , the RR changed by 22 % from 0.40 to 0.62 if angular displacement was added to the model , and by 9 % from 0.40 to 0.49 if angular velocity was added . For dynamic balance , it changed by 1 % from 0.40 to 0.41 if angular displacement was added , and by 14 % from 0.40 to 0.54 if angular velocity was added . Discussion Thus , balance assessment using trunk angular displacement is a valid method for the prediction of falls in older women . Of the observed 60 % reduction in the rate of falls by vitamin D plus calcium supplementation compared with calcium alone , up to 22 % of the treatment effect was explained by a change in postural balance and up to 14 % by dynamic balance", "OBJECTIVES To study the effect of alfacalcidol ( 1alpha(OH)D3 ) on fall risk in community-dwelling elderly men and women . DESIGN R and omized , double-blind , placebo-controlled intervention trial . SETTING Basel , Switzerl and . PARTICIPANTS Three hundred seventy-eight community-dwelling elderly ( 191 women/187 men ) . INTERVENTION Participants were r and omly assigned to receive 1 microg of alfacalcidol or matched placebo daily for 36 weeks . MEASUREMENTS Serum 25-hydoxyvitamin D3 ( 25(OH ) D,1,25-dihydroxyvitamin D3 ( D-hormone ) , and intact parathormone ( iPTH ) levels were measured using radioimmunoassay at baseline and every 12 weeks . Numbers of fallers and falls were assessed using a question naire during each study site visit . Dietary calcium intake was assessed at baseline using a food frequency question naire . RESULTS At baseline , participants had , on average , normal vitamin D and D-hormone serum levels . Over 36 weeks , alfacalcidol treatment was associated with fewer fallers ( odds ratio (OR)=0.69 , 95 % confidence interval (CI)=0.41 - 1.16 ) than placebo . In a post hoc subgroups analysis by medians of total calcium intake , this reduction reached significance in alfacalcidol-treated subjects with a total calcium intake of more than 512 mg/d ( OR=0.45 , 95 % CI=0.21 - 0.97 , P=.042 ) but not in those who consumed less than 512 mg/d ( OR=1.00 , 95 % CI= 0.47 - 2.11 , P=.998 ) . Alfacalcidol treatment was also , independent of total calcium intake , associated with a significant 37.9 % reduction in iPTH serum levels ( P hypercalcemia were observed . CONCLUSION Provided a minimal calcium intake of more than 512 mg/d , alfacalcidol treatment significantly and safely reduces number of fallers in an elderly community dwelling population", "BACKGROUND A recent meta- analysis found that cholecalciferol ( vitamin D ) should reduce falls by more than 20 % . However , little is known about whether supplemental cholecalciferol plus calcium citrate malate will lower the long-term risk of falling in men , active older individuals , and older individuals with higher 25-hydroxyvitamin D levels . METHODS We studied the effect of 3-year supplementation with cholecalciferol-calcium on the risk of falling at least once in 199 men and 246 women 65 years or older and living at home . Individuals received 700 IU of cholecalciferol plus 500 mg of calcium citrate malate per day or placebo in a r and omized double-blind manner . Subjects were classified as less physically active if physical activity was below the median level . Low 25-hydroxyvitamin D levels were classified as those below 32 ng/mL ( fall . Mean + /- SD baseline 25-hydroxyvitamin D levels were 26.6 + /- 12.7 ng/mL ( 66.4 + /- 31.7 nmol/L ) in women and 33.2 + /- 14.2 ng/mL ( 82.9 + /- 34.9 ) in men . Cholecalciferol-calcium significantly reduced the odds of falling in women ( odds ratio [ OR ] , 0.54 ; 95 % confidence interval [ CI ] , 0.30 - 0.97 ) , but not in men ( OR , 0.93 ; 95 % CI , 0.50 - 1.72 ) . Fall reduction was most pronounced in less active women ( OR , 0.35 ; 95 % CI , 0.15 - 0.81 ) . Baseline 25-hydroxyvitamin D level did not modulate the treatment effect . CONCLUSIONS Long-term dietary cholecalciferol-calcium supplementation reduces the odds of falling in ambulatory older women by 46 % , and especially in less active women by 65 % . Supplementation had a neutral effect in men independent of their physical activity level", "Specific receptors for vitamin D have been identified in human muscle tissue . Cross-sectional studies show that elderly persons with higher vitamin D serum levels have increased muscle strength and a lower number of falls . We hypothesized that vitamin D and calcium supplementation would improve musculoskeletal function and decrease falls . In a double-blind r and omized controlled trial , we studied 122 elderly women ( mean age , 85.3 years ; range , 63 - 99 years ) in long-stay geriatric care . Participants received 1200 mg calcium plus 800 IU cholecalciferol ( Cal+D-group ; n = 62 ) or 1200 mg calcium ( Cal-group ; n = 60 ) per day over a 12-week treatment period . The number of falls per person ( 0 , 1 , 2 - 5 , 6 - 7 , > 7 falls ) was compared between the treatment groups . In an intention to treat analysis , a Poisson regression model was used to compare falls after controlling for age , number of falls in a 6-week pretreatment period , and baseline 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum concentrations . Among fallers in the treatment period , crude excessive fall rate ( treatment - pretreatment falls ) was compared between treatment groups . Change in musculoskeletal function ( summed score of knee flexor and extensor strength , grip strength , and the timed up&go test ) was measured as a secondary outcome . Among subjects in the Cal+D-group , there were significant increases in median serum 25-hydroxyvitamin D ( + 71 % ) and 1,25-dihydroxyvitamin D ( + 8 % ) . Before treatment , mean observed number of falls per person per week was 0.059 in the Cal+D-group and 0.056 in the Cal-group . In the 12-week treatment period , mean number of falls per person per week was 0.034 in the Cal+D-group and 0.076 in the Cal-group . After adjustment , Cal+D-treatment accounted for a 49 % reduction of falls ( 95 % CI , 14 - 71 % ; p crude average number of excessive falls was significantly higher in the Cal-group ( p = 0.045 ) . Musculoskeletal function improved significantly in the Cal+D-group ( p = 0.0094 ) . A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49 % compared with calcium alone . Over this short-term intervention , recurrent fallers seem to benefit most by the treatment . The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function", "Summary In 242 community-dwelling seniors , supplementation with either 1000 mg of calcium or 1000 mg of calcium plus vitamin D result ed in a decrease in the number of subjects with first falls of 27 % at month 12 and 39 % at month 20 . Additionally , parameters of muscle function improved significantly . Introduction The efficacy of vitamin D and calcium supplementation on risk of falling in the elderly is discussed controversially . R and omized controlled trials using falls as primary outcome are needed . We investigated long-term effects of calcium and vitamin D on falls and parameters of muscle function in community-dwelling elderly women and men . Methods Our study population consisted of 242 individuals recruited by advertisements and mailing lists ( mean [ ± SD ] age , 77 ± 4 years ) . All serum 25-hydroxyvitamin D ( 25[OH]D ) levels were below 78 nmol/l . Individuals received in a double blinded fashion either 1000 mg of calcium or 1000 mg of calcium plus 800 IU of vitamin D per day over a treatment period of 12 months , which was followed by a treatment-free but still blinded observation period of 8 months . Falls were documented using diaries . The study took place in Bad Pyrmont , Germany ( latitude 52 ° ) and Graz , Austria ( latitude 46 ° ) . Results Compared to calcium mono , supplementation with calcium plus vitamin D result ed in a significant decrease in the number of subjects with first falls of 27 % at month 12 ( RR = 0.73 ; CI = 0.54–0.96 ) and 39 % at month 20 ( RR = 0.61 ; CI = 0.34–0.76 ) . Concerning secondary endpoints , we observed significant improvements in quadriceps strength of 8 % , a decrease in body sway of 28 % , and a decrease in time needed to perform the TUG test of 11 % . Discussion Combined calcium and vitamin D supplementation proved superior to calcium alone in reducing the number of falls and improving muscle function in community-dwelling older individuals", "The aim of the current study was to examine whether calcium supplementation could prevent bone loss in postmenopausal women or more favourable outcomes could be obtained via the consumption of dairy products fortified with calcium and vitamin D3 . For this purpose changes in bone mineral density ( BMD ) at different skeletal sites , assessed by dual-energy X-ray absorptiometry , as well as in quantitative ultrasound ( QUS ) parameters of the calcaneus over 12 months were estimated . A population of 101 postmenopausal women ( 55 - 65 years old ) was r and omized into a dairy group ( DG : n 39 ) , receiving approximately 1200 mg calcium/d and 7.5 microg vitamin D3/d through fortified dairy products ; a calcium-supplemented group ( CaG : n 26 ) provided with a calcium supplement of 600 mg/d ; and a control group ( CG : n 36 ) . Over the intervention period the DG was found to have more favourable changes in pelvis ( P=0.040 ) , total spine ( P total body BMD ( P lumbar spine BMD ( 2.0 % ; 95 % CI 0.5 , 3.5 ) although it did not differentiate significantly compared to the other groups . No significant differences were observed with respect to the changes in QUS parameters . The current study revealed that recommended intakes of vitamin D3 and calcium via fortified dairy products for 12 months can induce favourable changes in pelvis , total spine and total body BMD in postmenopausal women but not in QUS parameters . No such favourable changes were observed via supplementation of calcium alone", "Vitamin D deficiency is common in elderly persons , especially those with hip fracture [ 1 , 2 ] . It is caused by low exposure to sunshine , decreased synthesis of vitamin D3 in the aging skin , and a diet low in vitamin D [ 3 , 4 ] . The mean vitamin D intake in elderly persons in the Netherl and s is about 100 IU/d , half that of elderly persons in the United States [ 5 ] . Most of this vitamin D comes from margarine , which is the only vitamin D-supplemented food in the Netherl and s ( 3 IU/g ) . In vitamin D deficiency , the low serum concentration of 25-hydroxyvitamin D [ 25(OH)D ] leads to a low 1,25-dihydroxyvitamin D [ 1,25(OH)2D ] concentration and then to a higher serum parathyroid hormone concentration , especially in the winter [ 6 - 10 ] . Histologically , the increased parathyroid activity is associated with high bone turnover , leading to cortical bone loss and low density bone [ 5 , 11 ] , which may lead to hip fracture . We previously studied the effects of vitamin D supplementation in residents of a home for the elderly and residents of a nursing home [ 10 ] . Vitamin D3 , 400 IU/d , led to an adequate increase of the serum 25(OH)D concentration , to a small but significant increase of the serum 1,25(OH)2D concentration , and to a decrease of the serum concentration of intact parathyroid hormone . It was recently observed [ 12 , 13 ] that bone mineral density at the hip is positively related to serum 25(OH)D concentration in postmenopausal and elderly women . Therefore , it might be expected that vitamin D supplementation would increase bone mineral density in elderly persons deficient in vitamin D. In line with this expectation , it was shown that vitamin D supplementation prevented bone loss from the spine during the winter in postmenopausal women [ 14 ] . These results suggest that vitamin D supplementation may reduce the incidence of hip fractures , because bone strength shows a strong correlation with bone mineral density [ 15 ] . However , increasing bone mineral density through a therapeutic intervention does not necessarily lead to increased bone strength , as has been shown with sodium fluoride [ 16 ] . Bone structure and bone quality are also determinants of bone strength [ 17 ] , and falls are a risk factor for hip fractures [ 18 ] . Therefore , hip fracture should be the outcome criterion in studies on the effect of vitamin D supplementation . Intervention studies on the prevention of osteoporotic fractures necessitate large numbers of patients , because the outcome has an annual incidence of 0.5 % to 4 % in the elderly population [ 19 ] . We report the results of a large-scale , prospect i ve study on the effect of vitamin D supplementation on the incidence of hip and other osteoporotic fractures . Methods Participants The study included 2578 persons ( 1916 women and 662 men ) 70 years of age and older ( mean age SD , 80 6 years ; range , 70 to 97 years ) . Participants were recruited from general practitioners , from apartment houses for elderly persons , and from homes for elderly persons in Amsterdam and its vicinity . Persons recruited from practitioners were living independently ; those recruited from apartment houses and homes were receiving some care , but less than they would have received in a nursing home . Participants had to be reasonably healthy and able to give informed consent . Persons with a history of hip fracture or total hip arthroplasty , known hypercalcemia , sarcoidosis , or recent urolithiasis ( were not excluded . The spontaneous use of vitamin D supplements and multivitamins was discouraged , but the prescription practice s of the general practitioners were not altered . All vitamin use was carefully documented . The study was approved by the Ethical Review Board of the Vrije Universiteit Hospital , and all participants gave informed consent . Study Design After checking the inclusion and exclusion criteria and obtaining informed consent , the participants were r and omly assigned to receive either active treatment with vitamin D3 or placebo . The study was double-blind , and r and omization was done in blocks of 10 per general practice , apartment house , or home . R and omization lists were made using a computerized r and om-number generator . Lists in sealed envelopes were sent to the hospital pharmacy for assignment . Each participant took either one tablet per day that contained vitamin D3 , 400 IU , or one placebo tablet per day that was identical in appearance and taste to the vitamin tablet . After enrollment , the participants received the first container of tablets ( 210 tablets ) . The container was replaced every 6 months with a full container . All participants were also advised in writing to consume at least three servings of dairy products per day ( for example , 1 glass of milk , 1 cup of yogurt , and 1 slice of cheese ) to ensure a calcium intake of at least 800 to 1000 mg/d . The study was started in August 1988 . The last participant was enrolled in December 1990 , and all participants had stopped using study medication by December 1993 . The follow-up period had been planned to last no more than 3 years , but because the number of hip fractures during the study was lower than expected , a 6-month extension was planned . The study participants thus received medication for 3 to 3.5 years ; those who received it for 3.5 years were those who consented to the 6-month extension . Total follow-up was to a maximum of 4 years . Data collected at baseline included an outdoor activity score ( 1 equals going outdoors less than once a week ; 2 equals going outdoors 1 or 2 times per week ; and 3 equals going outdoors 3 times per week or more ) and a score for sunshine exposure ( when outside : 1 equals in the shade as much as possible ; 2 equals sometimes in sunshine ; 3 equals much exposure to sunshine ) . These scores show a positive relation with serum 25(OH)D concentration [ 3 ] . Mobility was estimated by a walking score that ranged from 1 ( unable to walk ) to 5 ( walks independently a fair distance on any surface ) [ 20 ] . The dietary calcium intake from dairy products was estimated in a subset of 348 women by using a question naire , as described previously [ 21 ] . The participants were evaluated annually with a question naire on hip fractures , other peripheral fractures , outdoor score , sunshine exposure score , use of vitamin supplements , and walking score . Each general practitioner or caretaker was asked to immediately report change of address , hip fracture , or death . Hip fracture and death were verified by the general practitioner . All participants were followed for the maximal period of 4 years if possible , even if they had stopped using the trial medication , had sustained a fracture , or had moved to another city . To investigate possible selection bias , 267 potential participants in a home for the elderly and its adjunct apartments ( all residents of the institution ) were studied for baseline characteristics , including age , sex , sunshine exposure score , outdoor score , walking score , and reasons for nonparticipation . Compliance was checked when the tablet containers were replaced ( every 6 months ) , by question naire ( every year ) , and by measurement of the serum 25(OH)D concentration . Serum 25(OH)D concentration was measured at baseline and after 1 year in 270 persons who participated in a sub study investigating the effect of vitamin D supplementation on bone mineral density and bone turnover variables . This sub study included a nonr and om sample of participants from several apartment houses and homes for the elderly and is described in detail elsewhere [ 21 ] . In the same sub study , dietary calcium intake from diary products was assessed . Serum 25(OH)D concentration was also estimated during the third year of the study in February and March in a r and om sample of 96 participants drawn from the remaining study population . These participants received a letter giving them an appointment within 10 days ; the blood sample s were drawn at home . Serum 25(OH)D concentration was measured by competitive protein binding assay after being purified by gradient high-pressure liquid chromatography . The intra- and interassay coefficients of variation were 5 % and 6 % , respectively [ 22 ] . Statistical Analysis Baseline data of the vitamin D group and the placebo group were compared using t-tests ( age , calcium intake ) , chi-square tests ( sex , residence ) , and Wilcoxon rank-sum tests ( scores ) . The serum 25(OH)D concentrations of both groups were compared using t-tests . Data on fractures and mortality were analyzed by survival analysis using log-rank tests , Cox proportional-hazards regression , and hazard rate ratios [ 23 ] . Hip fractures are presented using the Kaplan-Meier method . All participants were kept in the study as long as possible . The data were analyzed in two ways . The intention-to-treat analysis included all r and omly assigned participants for either the total follow-up period or until fracture , death , or loss to follow-up . The active treatment analysis included the participants as long as they stated that they were using the trial medication . Thus , the participants were included in the active treatment analysis until they stopped using the trial medication , regardless of whether a fracture occurred after they had stopped . Age , sex , and residence were added in both analyses as covariates to the Cox regression model . Because outdoor score , sunshine score , and walking score were interrelated ( correlation coefficients ranging from 0.21 to 0.59 ) and were likely to indicate general health or mobility , they were averaged over the years and added up to a sum score . For this purpose , the walking score was simplified ( 1 , 2 , or 3 equals 1 ; 4 equals 2 ; 5 equals 3 ) , because the lower walking scores applied to a few participants only . The result ing total score , ranging from 3 to 9 , was entered as a covariate in the model . The level of compliance ( weekly intake as reported on", "The long term effects of hormone replacement therapy ( HRT ) and vitamin D3 ( Vit D ) on bone mineral density ( BMD ) were studied . A total of 464 nonosteoporotic early postmenopausal women from the Kuopio Osteoporosis Study ( n = 13100 ) were r and omized to four groups : 1 ) HRT ( sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate , 2 ) Vit D3 ( 300 and 100 IU/day during the fifth year ) , 3 ) HRT and Vit D combined , and 4 ) placebo . Lumbar ( L2-L4 ) and femoral neck BMD were determined by dual x-ray absorptiometry ( DXA ) at baseline and after 2.5 and 5 yr of treatment . Intention to treat analysis ( n = 464 ) showed that after 5 yr , lumbar BMD remained unchanged in the HRT and HRT plus Vit D groups [ + 0.2 % ( P = 0.658 ) and + 0.9 % ( P = 0.117 ) , respectively ] , whereas lumbar BMD decreased by 4.6 % in the Vit D group and by 4.5 % in the placebo group ( P loss of femoral neck BMD was less in the HRT ( -1.4 % ; P = 0.005 ) and HRT plus Vit D ( -1.3 % ; P = 0.003 ) groups than in the Vit D and placebo groups ( -4.3 % ; P 370 women who complied with the 5-yr treatment , the effect was more pronounced : lumbar BMD had increased by 1.5 % in the HRT ( P = 0.009 ) and by 1.8 % in the HRT plus Vit D group ( P = 0.005 ) , with a plateau after 2.5 yr , whereas lumbar BMD had decreased in both the Vit D and placebo groups ( 4.6 % and 4.7 % ; P Femoral neck BMD decreased again less in the HRT ( -0.4 % ) and HRT plus Vit D ( -0.6 % ) groups than in the Vit D and placebo groups ( -4.4 % in both ) . This study confirms the positive long term effect of HRT on BMD also seen in intention to treat analysis . The data suggest that low dose vitamin D3 supplementation does not prevent bone loss in healthy , nonosteoporotic , early postmenopausal women , and it confers no benefit additional to that of HRT alone ", "BACKGROUND Vitamin D deficiency is common in older people and may increase risk of falls and fracture . Hospital in patients are at particular risk of falling . Previous studies suggest that vitamin D improves neuromuscular function and reduces falls . OBJECTIVE To determine whether routine supplementation with vitamin D plus calcium reduces numbers of fallers and falls in a cohort of hospital admissions while they are in patients . DESIGN R and omised , double-blind , controlled study . PARTICIPANTS two hundred and five acute admissions > 65 years to a geriatric medical unit . METHODS Patients were r and omised to intervention of daily vitamin D 800 iu plus calcium 1,200 mg or control group of daily calcium 1,200 mg , until discharge or death . RESULTS Baseline characteristics were similar in both groups with a median age 84 years and a median length of stay = 30 days ( IQR 14.75 - 71.00 ) . In a pre-selected sub-group ( 54/205 participants ) , median admission vitamin D level = 22.00 nmol/l ( IQR 15.00 - 30.50 ) . This did not significantly increase in the treatment versus control group . Median study drug adherence = 88 % , with no significant difference between study groups ( Mann-Whitney : P = 0.711 ) . Although there were fewer fallers in the vitamin D cohort , this did not reach statistical significance ( vitamin D : calcium = 36:45 fallers ; RR 0.82 ( CI 0.59 - 1.16 ) . Neither the mean number of falls ( vitamin D : calcium = 1.040:1.155 ; Mann-Whitney P = 0.435 ) or time to first fall ( Log-rank test P = 0.377 ) differed between groups . CONCLUSIONS In a population of geriatric hospital in patients , vitamin D did not reduce the number of fallers . Routine supplementation can not be recommended to reduce falls in this group", "BACKGROUND Vitamin D deficiency is common in older population s , particularly during the winter months due to low levels of ultraviolet light exposure , and in nursing home residents . OBJECTIVE The main objective of the current study was to assess the distribution of serum 25-hydroxyvitamin D and its correlates in a sample of men and women with recent hip fractures who were part of a large clinical trial . METHODS This was a cross-sectional exploratory study of screened and ultimately r and omized patients with hip fractures . They were part of a multinational ( 115 clinical centers in 20 countries ) , r and omized , placebo-controlled , double-blind study testing the efficacy of a yearly IV bisphosphonate ( zoledronic acid ) in the prevention of new clinical fractures in patients with recent hip fracture repair . Levels of 25-hydroxyvitamin D , calcium , alkaline phosphatase , creatinine clearance , and albumin were measured at a screening visit using blood serum . Demographic variables were assessed by patient self-report . Bone mineral density ( BMD ) was assessed by dual-energy x-ray absorptiometry of the nonfractured hip . RESULTS This report included 1174 screened patients ( 526 with vitamin D measured ) and 655 ( 385 with vitamin D measured ) patients r and omized before the protocol amendment . In screened patients , levels of 25-hydroxyvitamin D were low ( median , 14.7 ng/mL ; interquartilc range , 7.6 , 21.65 ) . Overall , 51 % were at or below the clinical ly meaningful threshold of 15 ng/mL. Among those patients r and omized , the level of 25-hydroxyvitamin D was significantly positively related to male sex ( rho , 0.13 ; P serum calcium ( rho , 0.16 ; P BMD at the femoral neck ( rho , 0.22 ; P Low serum 25-hydroxyvitamin D ( low serum calcium ( odds ratio , 0.16 ; 95 % CI , 0.05 - 0.52 ) in multivariable logistic models controlling for sex , age , race , body mass index , living at home , alkaline phosphatase , and creatinine clearance . CONCLUSIONS We concluded that vitamin D insufficiency was a common problem in this population of elderly patients who had recently suffered a hip fracture . This insufficiency was related only to serum calcium in multivariable controlled models but can not be reliably identified or excluded by measuring serum calcium alone . Physicians should be encouraged to check and monitor patients ' serum levels of 25-hydroxyvitamin", "OBJECTIVES Low trauma fractures in older people incur enormous physical , social and economic costs . Previous research indicates that an annual intramuscular injection of vitamin D may reduce fracture rates in this group . This strategy requires validation in a population setting . METHODS R and omized , double-blind , placebo-controlled trial of 300,000 IU intramuscular ( i.m . ) vitamin D2 ( ergocalciferol ) injection or matching placebo every autumn over 3 years . 9440 people ( 4354 men and 5086 women ) aged 75 yrs and over were recruited from general practice registers in Wessex , Engl and . Primary outcome measure was all non-vertebral fracture . Secondary outcomes were hip and wrist fractures , and all falls . RESULTS 585 subjects had incident non-spine fractures ( hip 110 , wrist 116 , ankle 37 ) . Hazard ratios ( HRs ) for fracture in the vitamin D group were : 1.09 [ 95 % confidence interval ( CI ) 0.93 - 1.28 , P = 0.29 ] for any first fracture , 1.49 ( 95 % CI 1.02 - 2.18 , P = 0.04 ) for hip and 1.22 ( 95 % CI 0.85 - 1.76 , P = 0.28 ) for wrist . There was no effect on falls : HR 0.98 ( 0.93 - 1.04 ) . No protective effect was observed in any subgroup when the cohort was stratified by sex , age , previous fracture or mobility . CONCLUSIONS An annual i.m . injection of 300,000 IU vitamin D2 is not effective in preventing non-vertebral fractures among elderly men and women resident in the general population", "The long-term effects of calcium and vitamin D supplementation on bone material and structural properties in older men are not known . The aim of this study was to examine the effects of high calcium ( 1000 mg/day)- and vitamin-D(3 ) ( 800 IU/day)-fortified milk on cortical and trabecular volumetric BMD ( vBMD ) and bone geometry at the axial and appendicular skeleton in men aged over 50 years . One hundred and eleven men who were part of a larger 2-year r and omized controlled trial had QCT scans of the mid-femur and lumbar spine ( L(1)-L(3 ) ) to assess vBMD , bone geometry and indices of bone strength [ polar moment of inertia ( I(polar ) ) ] . After 2 years , there were no significant differences between the milk supplementation and control group for the change in any mid-femur or L(1)-L(3 ) bone parameters for all men aged over 50 years . However , the mid-femur skeletal responses to the fortified milk varied according to age , with a split of 62 years being the most significant for discriminating the changes between the two groups . Subsequent analysis revealed that , in the older men ( > 62 years ) , the expansion in mid-femur medullary area was 2.8 % ( P milk supplementation compared to control group , which helped to preserve cortical area in the milk supplementation group ( between group difference 1.1 % , P mid-femur cortical vBMD and I(polar ) , the net loss was 2.3 and 2.8 % less in the milk supplementation compared to control group ( P calcium-vitamin-D(3)-fortified milk may represent an effective strategy to maintain bone strength by preventing endocortical bone loss and slowing the loss in cortical vBMD in elderly men", "A two-year double-blind study monitored and evaluated the effects of 1 alpha-hydroxy vitamin D3 ( 1 alpha(OH)D3 ) on the lumbar ( L2 - 4BMD ) and total body bone mineral densities ( TBBMD ) and occurrence of fracture in 113 female osteoporotic patients receiving 0.75 micrograms/day of 1 alpha(OH)D3 ( n = 57 ) or a placebo ( n = 56 ) with calcium supplementation in both groups . L2 - 4BMD increased 1.81.% and 2.32 % after one and 2 years in the 1 alpha (OH)D3 group , but decreased 1.89 % ( P TBBMD decreased significantly in the placebo group by 3.34 % ( P new fractures occurred in the control group , but only two in the 1 alpha(OH)D3 group ( Odd 's ratio = 0.343 , 95 % confidence range ; 0.0648 - 1.815 ) . There were no serious adverse effects of the 1 alpha(OH)D3 treatment . It was concluded that two-year treatment with 1 alpha(OH)D3 increased the lumbar BMD and inhibited the decrease in TBBMD . Although it was not significant , new fracture occurrence in the 1 alpha(OH)D3 group was around 1/3 of that in the control group", "The efficacy of calcium ( Ca ) in reducing bone loss is debated . In a r and omized placebo-controlled double-masked study , we investigated the effects of oral Ca supplements on femoral shaft ( FS ) , femoral neck ( FN ) and lumbar spine ( LS ) bone mineral density ( BMD ) , and on the incidence of vertebral fracture in vitamin-D-replete elderly . Ninety-three healthy subjects ( 72.1±0.6 years ) were r and omly allocated to three groups receiving 800 mg/day Ca in two different forms or a placebo for 18 months . Sixty-three patients ( 78.4±1.0 years ) with a recent hip fracture were allocated to two groups receiving the two forms of Ca without placebo . FS BMD changes in Ca-supplemented non-fractured women were significantly different from those in the placebo group ( + 0.6±0.5 % v −1.2±0.7%,p of Ca . The changes of + 0.7±0.8 % v −1.7±1.6 % in FN BMD of Ca-supplemented women and the placebo group did not reach statistical significance . In fractured patients , FS , FN and LS BMD changes were −1.3±0.8 , + 0.3±1.6 and + 3.1±1.2 % ( p . The rate of new vertebral fractures was 74.3 and 106.2 fractures per 1000 patient-years in Ca-supplemented non-fractured subjects and in the placebo group , respectively , and 144.0 in Ca-supplemented fractured patients . Thus , oral Ca supplements prevented a femoral BMD decrease and lowered vertebral fracture rate in the elderly", "To evaluate the efficacy and safety of 1-alpha(OH ) vitamin D3 in the treatment of postmenopausal osteoporosis , we conducted a six month prospect i ve , double blind study in 20 postmenopausal women . Women were r and omly divided into two groups . One group ( n=12 ) received 1-alpha(OH ) vitamin D3 ( 0.25 mcg twice a day ) , the other ( n=8 ) received placebo . At the same time both groups received one calcium tablet ( 500 mg daily ) . In the group treated with 1-alpha(OH ) vitamin D3 , there was a significant increase in serum calcium ( p urinary excretion of calcium ( p serum 1.25(OH)2 vitamin D3 concentracion ( p parathyroid hormone levels showed tendency to fall without statistical significance . In the group treated with placebo and calcium , after treatment there was only a significant increase in serum calcium ( p placebo group occurrance of one new vertebral fracture was recorded . There were no side effects during treatment in both groups . It was concluded that the administration of 1-alpha(OH ) vitamin D3 is a safe and potentially efficient drug in the treatment of postmenopausal osteoporosis ", "The therapeutic effect of 1,25-dihydroxycholecalciferol ( 1,25(OH)2D3 ) in postmenopausal osteoporosis was tested in a single blind , r and omized prospect i ve study . Thirty-nine women , 50 - 65 years of age , were treated for three years with 0.5 microgram 1,25(OH)2D3 daily . In a control group , 37 women were given 400 IU vitamin D3 daily . There was no significant difference in annual bone loss from the distal or proximal forearm between the groups . New vertebral fractures were evaluated , and in the treatment group , the annual increase in vertebral fractures was 0.18 + /- 0.387 and in the control group 0.13 + /- 0.330 . New long bone fractures were 7 and 5 , respectively . None of the observed differences were statistically significant . In the 1,25(OH)2D3 group , 28 % had to reduce the dose because of slight hypercalcaemia . We conclude that 1,25(OH)2D3 as used in this study is not effective in the treatment of osteoporosis", "Summary In order to investigate the effect of a supplementation of vitamin D in the prophylaxis of fractures of the bones of aged people , an annual intramuscular injection of ergocalciferol ( 150,000–300,000 IU ) was given to two series of aged subjects : first to 199 ( 45 male ) of 479 subjects ( 110 male ) aged more than 85 years who were living in their own home , and second to 142 ( 29 male ) of 320 ( 58 male ) subjects aged 75–84 and living in a home for aged people . This prospect i ve series was divided into treatment groups according to month of birth . These injections were given annually from September to December in the years 1985–1989 , two to five times to each participant . The fracture rates , laboratory values , vitamin D levels , possible side effects , and mortality were followed until October 1990 . A total of 56 fractures occurred in the 341 vitamin D recipients ( 16.4 % ) and 100 in 458 controls ( 21.8 % ) ( P=0.034 ) . The fracture rate was about the same in both outpatient and municipal home series . Fractures of the upper limb were fewer in the vitamin D recipients , 10/341=2.9 % ( P=0.025 ) , than in the controls , 28/458=6.1 % , during the follow-up . A similar result was obtained in fractures of ribs , 3/341=0.9 % and 12/458=2.6 % , respectively . Fractures of the lower limbs occurred almost as frequently , 31/341=9.1 % , among the vitamin D recipients as among the controls , 49/458=10.7 % . The fracture rate was higher in females ( 22.2 % ) than in males ( 9.5 % ) . The fractures were fewer in the vitamin D recipients only in females . No significant differences were found in total mortality , or due to any group of diseases , between the two treatment groups . No deleterious effects of the vitamin D injections were seen . The authors recommend the supplementation of vitamin D in aged people , at least in northernmost latitudes ( e.g. , as an annual intramuscular injection )", "To examine whether the administration of 1 alpha (OH)-vitamin D3 ( 1 alpha (OH)D3 ) could prevent the occurrence of vertebral crush fractures in senile osteoporosis , crush fractures of the thoracic or lumbar spine in senile osteoporosis treated with 1 alpha (OH)D3 , 1.0 microgram/day ( 22 cases ) , 1 alpha (OH)D3 1.0 microgram/day + Ca 1.0 g/day ( 16 cases ) or Ca 1.0 g/day ( 23 cases ) were compared with those in non-treated controls ( 25 cases ) . The average treatment periods were 1.7 + /- 0.7 years in the 1 alpha (OH)D3 group , 2.1 + /- 1.0 years in the 1 alpha (OH)D3 + Ca group and 1.7 + /- 0.9 years in the Ca group . Occurrence of spinal crush fractures per 1000 patient years was significantly less in the 1 alpha (OH)D3 + Ca group ( P less than 0.01 ) than in the non-treated control group . These findings suggest that administration of 1 alpha (OH)D3 is effective in preventing the occurrence of pathological fractures in senile osteoporosis", "To evaluate the effects of calcium and 25-OHD in the therapy of senile osteoporosis , we studied a group of 39 women aged 69 + /- 7 ( st and ard deviation , SD ) years with severe osteoporosis . The group was characterized histomorphometrically by depressed bone remodeling rates without hyperosteoidosis . No subject had risk factors for osteopenia other than their age and postmenopausal status , and no subject was receiving therapy for bone disease at the onset of the study . Subjects were followed for 2 years after r and omization to receive either 1200 mg/day of calcium ( as calcium carbonate ) and 40 micrograms/day of 25-OHD ( calcium-25-OHD group ) , or 1200 mg/day of calcium plus placebo ( calcium-placebo group ) . Calcium-25-OHD result ed in a clear increase in 25-OHD levels ( p less than 0.001 ) and an increase in calcium absorption as indicated by urinary calcium excretion . Nevertheless , there was no significant change in fasting serum calcium , phosphorus , alkaline phosphatase , PTH , or 1,25-(OH)2D in either group . Radial and phalangeal bone mineral content and trabecular bone volume in the biopsied patients remained stable in both groups over the 2 year period . Unexpectedly , repeat bone biopsies revealed a clear improvement in the rate of mineralization in both groups , presumably as a result of the calcium supplementation alone . In summary , calcium-placebo and calcium-25-OHD treatment were both associated with stable appendicular bone mineral content in women with senile osteopenia . The finding of an effect of calcium supplementation on the rate of mineralization indicates that relative calcium deficiency may impair the mineralization phase of remodeling . ( ABSTRACT TRUNCATED AT 250 WORDS", "OBJECTIVES To investigate the effect of vitamin K2 treatment for a year on spinal bone mineral density ( BMD ) in postmenopausal women , comparing with vitamin D3 hormone replacement therapy and to determine the factors which affect the efficacy of vitamin K2 therapy . SUBJECTS AND METHODS Seventy-two postmenopausal women were r and omized into four groups and treated with respective agents . Before the therapy , 6 and 12 months after the treatment , their lumbar spine BMD were measured by dual energy X-ray absorptiometry . The rates of change in BMD ( delta BMD ) were calculated . Correlations of BMD with age , year since menopause and the initial BMD were determined . RESULTS Vitamin K2 suppressed the decrease in spinal BMD as compared with no treatment group . BMD in women treated with vitamin K2 was inversely correlated with their age ( r = -0.54 ; P Vitamin K2 therapy may be a useful method for preventing postmenopausal spinal bone mineral loss . In addition , the therapy should be started early in postmenopausal period", "OBJECTIVE Patients with osteoarthritis ( OA ) have increased bone mineral density ; however , the association between knee OA and fracture is controversial . Few data exist on the association between knee pain and fracture . We examined the association of knee OA and knee pain with fracture and falls in elderly men and women . METHODS The study group comprised 6,641 men and women ages > or = 75 years who participated in a 3-year r and omized controlled trial of intramuscular vitamin D therapy . Patients completed a question naire about knee pain and OA . Fracture and fall data were collected prospect ively every 6 months . RESULTS Knee pain prevalence and a clinician diagnosis of knee OA were 35.2 % and 6.8 % , respectively . A total of 436 incident nonvertebral fractures were reported , and 3,992 patients sustained a fall . Prevalent knee pain was associated with an increased risk of falls ( hazard ratio [ HR ] 1.26 , 95 % confidence interval [ 95 % CI ] 1.17 - 1.36 ) and hip fracture ( HR 2.0 , 95 % CI 1.18 - 3.37 ) . Increasing severity of knee pain was associated with a greater risk of falls and hip fracture . Clinician diagnosis of knee OA was associated with an increased risk of nonvertebral fractures ( HR 1.61 , 95 % CI 1.09 - 2.36 ) . The increased risk of fracture was not substantially reduced by adjusting for falls , but was attenuated by adjustment for the use of walking aids . CONCLUSION Patients with a clinical diagnosis of knee OA and with knee pain have an increased risk of nonvertebral and hip fracture . This is not explained by the increased risk of falls , but is more likely to be due to the severity of falls sustained . Knee pain and OA should be regarded as independent risk factors for fracture", "There is an increase in the incidence of falls with aging and about 10 % of falls lead to fractures . Nearly all hip fractures are due to falls and hip fractures are the most severe of the osteoporotic fractures because they lead to a 20 % mortality rate and a loss of independent living in 50 % of cases . Although there are multiple factors associated with falls , our interest is the role that vitamin D metabolism plays in the pathogenesis of falls . Recent clinical trials show that both vitamin D and the metabolite calcitriol reduce the number of falls by 30 - 40 % in elderly subjects . This should also reduce the number of fractures . In European studies , the decrease in falls could be attributed to an improvement in the muscle weakness that often accompanies vitamin D deficiency . However , in the studies using calcitriol there was no vitamin D deficiency , so the mechanism of its efficacy is less clear . It could be due to increased muscle strength , an improvement in the neurological control of balance or both . Underst and ing these mechanisms would allow us to search for analogs of vitamin D that act more selectively on muscle and on the central nervous system", "OBJECTIVES To study the effects of vitamin D supplementation in healthier population s of men . DESIGN : R and omized , controlled trial . SETTING General clinical research center . PARTICIPANTS Sixty-five healthy , community-dwelling men ( mean age+/-st and ard deviation=76+/-4 , range 65 - 87 ) . INTERVENTION Cholecalciferol ( 1,000 IU/d ) or placebo supplementation for 6 months ; all received 500 mg supplemental calcium . MEASUREMENTS Upper and lower extremity muscle strength and power , physical performance and activity , health perception , calcium and vitamin D intake , and biochemical assessment , including 25-hydroxyvitamin D ( 25OHD ) , parathyroid hormone ( PTH ) , and ionized calcium levels . RESULTS The levels of 25OHD increased and PTH decreased in the cholecalciferol group , whereas there were no significant changes in the control group ( P Baseline 25OHD levels correlated with baseline single-leg stance time and physical activity score . Baseline PTH levels correlated with baseline 8-foot walk time and physical activity score . No significant difference in strength , power , physical performance , or health perception was found between groups . CONCLUSION The 25OHD or PTH levels correlated with physical activity and physical performance in older , community-dwelling men with normal 25OHD status . Vitamin D supplementation increased 25OHD levels and decreased PTH levels but did not increase muscle strength or improve physical performance or health perception in this group of healthy , older men . Further investigations of the effects of vitamin D supplementation should focus on individuals with low levels of vitamin", "BACKGROUND We conducted a r and omized , placebo-controlled , double-blind trial to test the hypothesis that vitamin D(3 ) supplementation would prevent bone loss in calcium-replete , African American postmenopausal women . METHODS Two hundred eight healthy black postmenopausal women , 50 to 75 years of age , were assigned to receive either placebo or 20 microg/d ( 800 IU ) of vitamin D(3 ) . Calcium supplements were provided to ensure a total calcium intake of 1200 to 1500 mg/d . After 2 years , the vitamin D(3 ) dose was increased to 50 microg/d ( 2000 IU ) in the active group , and the study continued for an additional year . Bone mineral density ( BMD ) was measured every 6 months . Markers of bone turnover , vitamin D metabolites , and parathyroid hormone ( PTH ) levels were measured in serum . RESULTS There were no significant differences in BMD between the active and control groups throughout the study . There was also no relationship between serum 25-hydroxyvitamin D levels attained and rates of bone loss . There was an increase in BMD of the total body , hip , and radius at 1 year in both groups . Over the 3 years , BMD declined at these sites by 0.26 % to 0.55 % per year . The BMD of the lumbar spine increased slightly in the placebo and active groups . There were no persistent changes in serum PTH levels or the markers of bone turnover , although there was a transient decline in PTH in both groups at 3 months . No significant adverse events were attributed to vitamin D supplementation . CONCLUSIONS There was no observed effect of vitamin D(3 ) supplementation on bone loss or bone turnover markers in calcium-replete , postmenopausal African American women . Further studies are needed to determine if these findings are applicable to women of other ethnic groups", "Antifracture efficacy of high-dose vitamin D ( 800 IU ) and calcium ( 1000 mg ) remains controversial . To determine whether daily 800 IU of vitamin D and 1000 mg of calcium supplementation prevents fractures , we r and omized 3432 women of the population -based Osteoporosis Risk Factor and Prevention ( OSTPRE ) Study cohort ( ages 65 to 71 years ) living in the region of northern Savonia , Finl and ( latitude 62 degrees to 64 degrees N ) for 3 years to receive 800 IU of cholecalciferol and 1000 mg of calcium as calcium carbonate or to a control group that did not receive placebo . The main outcome measure was incident fractures . Fracture data were collected in telephone interviews and vali date d. Data on 3195 women , 1586 in the intervention group and 1609 in the control group , were available for analysis . In adjusted Cox proportional hazards models , the risk of any fracture decreased in the vitamin D and calcium group by 17 % [ adjusted hazard ratio ( aHR ) = 0.83 ; 95 % confidence interval ( CI ) 0.61 - 1.12 ] , and the risk of any nonvertebral fracture decreased by 13 % ( aHR = 0.87 ; 95 % CI 0.63 - 1.19 ) . The risk of distal forearm fractures decreased by 30 % ( aHR = 0.70 ; 95 % CI 0.41 - 1.20 ) , and the risk of any upper extremity fractures decreased by 25 % ( aHR = 0.75 ; 95 % CI 0.49 - 1.16 ) , whereas the risk of lower extremity fractures remained essentially equal ( aHR = 1.02 ; 95 % CI 0.58 - 1.80 ) . None of these effects reached statistical significance . In conclusion , this study did not produce statistically significant evidence that vitamin D and calcium supplementation prevents fractures in a 65- to 71-year-old general population of postmenopausal women", "CONTEXT Mono- and polyunsaturated fats may have opposing effects on vitamin D absorption . OBJECTIVE The purpose of this study was to determine whether intakes of different dietary fats are associated with the increase in serum 25-hydroxyvitamin D ( 25OHD ) after supplementation with vitamin D(3 ) . DESIGN , SETTING , AND PARTICIPANTS This analysis was conducted in the active treatment arm of a r and omized , double-blind , placebo-controlled trial of vitamin D and calcium supplementation to prevent bone loss and fracture . Subjects included 152 healthy men and women age 65 and older who were assigned to 700 IU/d vitamin D(3 ) and 500 mg/d calcium . Intakes of monounsaturated fatty acids ( MUFA ) , polyunsaturated fatty acids ( PUFA ) , and saturated fatty acids ( SFA ) were estimated by food frequency question naire . MAIN OUTCOME MEASURE The change in plasma 25OHD during 2 yr vitamin D and calcium supplementation was assessed . RESULTS The change in plasma 25OHD ( nanograms per milliliter ) during vitamin D supplementation was positively associated with MUFA , ( β = 0.94 ; P = 0.016 ) , negatively associated with PUFA , ( β = -0.93 ; P = 0.038 ) , and positively associated with the MUFA/PUFA ratio ( β = 6.46 ; P = 0.014 ) . CONCLUSION The fat composition of the diet may influence the 25OHD response to supplemental vitamin D(3 ) . Diets rich in MUFA may improve and those rich in PUFA may reduce the effectiveness of vitamin D(3 ) supplements in healthy older adults . More studies are needed to confirm these findings", "BACKGROUND Frequent use of personal , non protocol calcium supplements obscured an adverse effect of coadministered calcium and vitamin D ( CaD ) on cardiovascular risk in the Women 's Health Initiative ( WHI ) . OBJECTIVE We investigated the effects of the use of personal calcium or vitamin D supplements on other outcomes in the WHI CaD Study ( WHI CaD ) by using the WHI limited-access clinical trials data set . DESIGN The WHI CaD was a 7-y , r and omized , placebo-controlled trial of CaD ( 1 g Ca/400 IU vitamin D daily ) in 36,282 community-dwelling , postmenopausal women . The incidence of total cancer ( excluding nonmelanoma skin cancers ) , breast and colorectal cancers , hip and total fracture , and mortality was assessed by using Cox proportional hazards models . RESULTS In the WHI CaD , interactions between the use of either personal calcium or vitamin D supplements and CaD were found for total , breast , and colorectal cancers but not for fracture or mortality . In 15,646 women ( 43 % ) who were not taking personal calcium or vitamin D supplements at r and omization , CaD significantly decreased the risk of total , breast , and invasive breast cancers by 14 - 20 % and nonsignificantly reduced the risk of colorectal cancer by 17 % . In women taking personal calcium or vitamin D supplements , CaD did not alter cancer risk ( HR : 1.06 - 1.26 ) . CONCLUSIONS For women in the WHI CaD who were not taking personal calcium or vitamin D supplements at r and omization , CaD decreased the risk of total , breast , and colorectal cancers and did not change the risk of fractures or total mortality . The nonskeletal effects of CaD may be more important than the skeletal effects and should be considered when evaluating these supplements . The WHI CaD trial is registered at clinical trials.gov as NCT00000611", "Malabsorption of calcium is a common finding in patients with postmenopausal osteoporosis ( 1 , 2 ) . In a number of studies serum 1,25 dihydroxyvitamin D levels were found to be significantly lower in osteoporotic patients , which could account for the calcium absorptive defect ( 3–6 ) . Based on these findings , we studied the effects of synthetic calcitriol ( Rocaltrol ) in women with osteoporosis . We showed that calcitriol , 0.25 μg twice daily , improved and normalized the absorption of calcium in all patients and improved calcium balance ( 7 ) . Urine hydroxyproline , which is a measure of bone resorption , decreased significantly after 2 years of treatment with Rocaltrol . Because of these preliminary findings , further clinical studies were carried out at two centers using a variable dose of Rocaltrol . In these studies we focused on the effectiveness of Rocaltrol in preventing vertebral fractures in patients with spinal osteoporosis . Methods The results from two centers have been analyzed both as separate groups and as one combined group . One study was performed at the Mayo Clinic ( Protocol 861 ) and the other at Creighton University ( Protocol 860 ) . In both centers the studies performed were double blind and r and omized , and compared the effect of placebo against Rocaltrol for a period of 1 year . At the end of 1 year all patients on placebo were crossed over to treatment with Rocaltrol and followed for 2 more years . Patients initially treated with Rocaltrol were followed for an additional 2 years , thus yielding treatment data extending to 3 years in a number of patients . In the study design , patients were given Rocaltrol at a starting dose of 0.25 μg twice daily , if hypercalcemia and hypercalciuria did not occur the dose then was increased to 0.75 μg or 1.0 μg daily at the discretion of the investigator", "OBJECTIVES To determine the effectiveness of vitamin D and home-based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge . DESIGN Multicenter , r and omized , controlled trial with a factorial design . SETTING Five hospitals in Auckl and , New Zeal and , and Sydney , Australia . PARTICIPANTS Two hundred forty-three frail older people . INTERVENTIONS Patients were r and omized to receive a single dose of vitamin D ( calciferol , 300,000 IU ) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits . MEASUREMENTS The primary endpoints were physical health according to the short-form health survey at 3 months and falls over 6 months . Physical performance and self-rated function were secondary endpoints . Assessment s took place in the participants ' homes at 3 and 6 months after r and omization and were performed by blinded assessors . RESULTS There was no effect of either intervention on physical health or falls , but patients in the exercise group were at increased risk of musculoskeletal injury ( risk ratio = 3.6 , 95 % confidence interval = 1.5 - 8.0 ) . Vitamin D supplementation did not improve physical performance , even in those who were vitamin D deficient ( vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved rehabilitation outcomes in frail older people after hospitalization . There was no effect of vitamin D on physical performance , and the exercises increased the risk of musculoskeletal injury . These findings do not support the routine use of these interventions at these dosages in the rehabilitation of frail older people", "The progress of spinal bone loss was monitored by measurements of the vertebral body height of T6 to L5 in seventy 70-year-old women who participated in a controlled , double-blind therapeutic trial . They were treated for one year by 1,25(OH)2D3 , 0.50 micrograms a day ( or less if hypercalcemia occurred ) and cyclical estrogen/gestagen , alone or combined , or placebo . Sufficient calcium intake was ensured in all . The vertebral body height decreased significantly , by 1 % , in both of the 1,25(OH)2D3 groups , whereas it remained unchanged in the hormone and the placebo + calcium group . This observation does not encourage the use of 1,25(OH)2D3 for prevention or treatment of postmenopausal bone loss", "Osteoporosis in men is an emerging public health problem . As calcitriol reduces the rate of vertebral fractures in osteoporotic postmenopausal women , we conducted a prospect i ve study of this treatment in men with primary osteoporosis . Our study was a 2-yr , r and omized , double masked , double placebo-controlled trial of calcitriol ( 0.25 microg twice daily ) or calcium ( 500 mg twice daily ) in 41 men with primary osteoporosis and at least 1 baseline fragility fracture . Thirty-three men ( 85 % ) completed the study . There were no differences in baseline characteristics . Spinal and femoral neck bone mineral densities at 2 yr were unchanged in both groups . Serum osteocalcin decreased in both groups by 30 % ( P urine N-telopeptide cross-links decreased only in the calcium group by 30 % ( P fractional calcium absorption increased by 34 % ( P fragility fractures occurred ( 14 vertebral and 5 nonvertebral ) in 7 men . Over 2 yr , the number of men with vertebral fractures ( 6 vs. 1 ; P = 0.097 ) was similar in both groups . In conclusion , the efficacy of calcitriol remains unproven as a single agent for the treatment of osteoporosis in men", "R and omized controlled trials have shown that a combination of vitamin D and calcium can prevent fragility fractures in the elderly . Whether this effect is attributed to the combination of vitamin D and calcium or to one of these nutrients alone is not known . We studied if an intervention with 10 microg of vitamin D3 per day could prevent hip fracture and other osteoporotic fractures in a double-blinded r and omized controlled trial . Residents from 51 nursing homes were allocated r and omly to receive 5 ml of ordinary cod liver oil ( n = 569 ) or 5 ml of cod liver oil where vitamin D was removed ( n = 575 ) . During the study period of 2 years , fractures and deaths were registered , and the principal analysis was performed on the intention-to-treat basis . Biochemical markers were measured at baseline and after 1 year in a sub sample . Forty-seven persons in the control group and 50 persons in the vitamin D group suffered a hip fracture . The corresponding figures for all nonvertebral fractures were 76 persons ( control group ) and 69 persons ( vitamin D group ) . There was no difference in the incidence of hip fracture ( p = 0.66 , log-rank test ) , or in the incidence of all nonvertebral fractures ( p = 0.60 , log-rank test ) in the vitamin D group compared with the control group . Compared with the control group , persons in the vitamin D group increased their serum 25-hydroxyvitamin D concentration with 22 nmol/liter ( p = 0.001 ) . In conclusion , we found that an intervention with 10 microg of vitamin D3 alone produced no fracture-preventing effect in a nursing home population of frail elderly people", "BACKGROUND survivors of hip fracture are at 5- to 10-fold risk of a second hip fracture . There is little consensus about secondary prevention . Many are given calcium and vitamin D , but the evidence supporting this is circumstantial . OBJECTIVE to compare the effects of different calcium and vitamin D supplementation regimens on bone biochemical markers , bone mineral density and rate of falls in elderly women post-hip fracture . DESIGN r and omised controlled trial . SETTING orthogeriatric rehabilitation ward . METHODS 150 previously independent elderly women , recruited following surgery for hip fracture , were assigned to receive a single injection of 300,000 units of vitamin D(2 ) , injected vitamin D(2 ) plus 1 g/day oral calcium , 800 units/day oral vitamin D(3 ) plus 1 g/day calcium , or no treatment . Follow-up was one year , with measurement of 25-hydroxyvitamin D , parathyroid hormone , bone mineral density , and falls . RESULTS mean 25-hydroxyvitamin D increased and mean parathyroid hormone was suppressed in all the actively treated groups , more so in the group receiving combined oral vitamin D and calcium . Twenty per cent of participants injected with vitamin D were deficient in 25-hydroxyvitamin D a year later . Bone mineral density showed small but statistically significant differences of up to 4.6 % between actively treated groups and placebo . Relative risk of falling in the groups supplemented with vitamin D was 0.48 ( 95 % CI 0.26 - 0.90 ) compared with controls . CONCLUSION Vitamin D supplementation , either orally or with injected vitamin D , suppresses parathyroid hormone , increases bone mineral density and reduces falls . Effects may be more marked with calcium co-supplementation . The 300,000 units of injected vitamin D may not last a whole year", "The effect of two different estrogen/gestagen regimens and 24R,25-(OH)2-cholecalciferol on bone formation was studied in a r and omized trial with 144 healthy postmenopausal women . Urinary excretion ( UE ) of 99m-technetium-diphosphonate and serum alkaline phosphatase ( AP ) was determined before and then once a year for 2 years of treatment . Both estimates of bone formation showed highly significant decreases ( p less than .001 ) to normal premenopausal levels in women receiving unopposed 17 beta-estradiol or in a sequential combination with progestagen , whereas unchanged high values were found in the groups receiving 24R,25-(OH)2D3 and placebo . The data show that bone turnover increases in early postmenopausal women concomitantly with the loss of bone mass , and that hormonal substitutional therapy normalizes the total skeletal turnover as well as preventing bone loss", "Osteoporosis is a major public health issue leading to significant morbidity , loss of independence and excess loss of life . It has been estimated that 13 to 17 million postmenopausal women have low bone mass or osteoporosis ( 1 , 2 ) . This is associated with almost 1.5 million fractures annually , including 300,000 hip fractures ( 2 , 3 ) . A review of the evidence by Cumming in 1990 ( 4 ) and subsequently published r and omized clinical trials have shown that calcium and /or vitamin D supplements may play a role in the prevention and treatment of osteoporosis by slowing the rates of bone loss in postmenopausal and elderly women ( 5–9 ) . However , there are a limited number of calcium and /or vitamin D trials ( 10–13 ) and observational studies [ review of evidence by Cumming and Nevitt ( 14 ) and Kanis ( 15 ) ] , to support a role for calcium and vitamin D supplementation in the reduction of hip and other fractures . It has also been suggested that calcium and vitamin D supplementation may play a role in the reduction of colorectal cancer incidence ( 16–21 ) . To address these major health concerns of postmenopausal women , the Calcium-Vitamin D ( CaD ) trial of the Women ’s Health Initiative ( WHI ) was design ed to test the primary hypothesis that women who are r and omized to receive calcium and vitamin D supplementation will have a lower risk of hip fracture and secondarily , a lower risk of all fractures and colorectal cancer than women receiving corresponding placebo . The objective of this paper is", "Background In r and omized trials there may be no overriding reason whether or not to have a placebo control . Purpose We assessed the effects of an open trial design ( no placebo and people know what tablets they are given ) compared with a blinded , placebo-controlled design on recruitment , compliance and retention within a r and omized trial of secondary osteoporotic fracture prevention . Methods We undertook a r and omized controlled comparison nested within a placebo-controlled trial of nutritional supplementation amongst people aged 70 years or over who had previously sustained a fracture , recruited in a UK teaching hospital . R and omization was 2 : 1 in favour of the blinded , placebo-controlled trial design . Results From 180 eligible participants r and omized to receive information based on the open trial design , 134 ( 74.4 % ) consented to take part , compared with 233 ( 65.1 % ) of 358 people r and omized to the blinded , placebo-controlled design ( difference 9.4 % , 95 % confidence interval 1.3–17.4 % ) . Reluctance to take a placebo and the desire to know tablet allocation were reasons given for not taking part in the blinded , placebo-controlled design . There was no significant difference in tablet compliance . Open trial participants were more likely to remain in the trial for one year ( difference 13.9 % , 95 % confidence interval 3.1–24.6 % ) , mainly reflecting the high retention of the open trial no tablet group compared to the open trial tablet group ( difference 23.6 % , 95 % confidence interval 11.9–35.2 % ) . The odds ratio for reporting an adverse event in the open trial compared to the blinded , placebo-controlled design was 0.64 ( 95 % confidence interval 0.28–1.49 ) , and for reporting a fracture was 0.81 ( 0.36–1.85 ) . Conclusions We conclude that using an open trial design may enhance participant recruitment and retention and thus improve generalizability and statistical power , but withdrawal rates may differ between the study allocations and may threaten the internal validity of the trial", "OBJECTIVE To evaluate functional improvement in a population of frail , homebound older persons with low vitamin D status as vitamin D stores improve . DESIGN R and omized , controlled intervention study . SETTING Subjects ' homes and a nursing facility in Baltimore , Maryl and . PARTICIPANTS The first 32 subjects ( community-dwelling , homebound older subjects from the Johns Hopkins Elder Housecall Program and nursing home residents from the Johns Hopkins Geriatrics Center ) entered in a longitudinal study of vitamin D replacement . MEASUREMENTS Baseline 25-hydroxyvitamin D levels were measured and repeated at least 1 month after therapy with either placebo or vitamin D ( ergocalciferol ) . Subjects were also administered the Frail Elderly Functional Assessment ( FEFA ) question naire , an instrument demonstrated to be reliable , valid , and sensitive to small increments of functional change in this population . MAIN RESULTS All subjects started with 25-hydroxyvitamin D levels less than 15 ng/mL. Those subjects whose levels improved by at least 3 ng/mL ( > assay coefficient of variation ) also demonstrated improvement in FEFA score . Regression analysis between change in FEFA score compared with change in 25-hydroxyvitamin D was significant ( r = .4 ; P = .02 ) . CONCLUSIONS In this cohort of homebound older people , improvement in vitamin D status was associated with functional improvement as measured by the FEFA question naire", "BACKGROUND Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons . METHODS We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density , biochemical measures of bone metabolism , and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home . They received either 500 mg of calcium plus 700 IU of vitamin D3 ( cholecalciferol ) per day or placebo . Bone mineral density was measured by dual-energy x-ray absorptiometry , blood and urine were analyzed every six months , and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records . RESULTS The mean ( + /-SD ) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows : femoral neck , + 0.50+/-4.80 and -0.70+/-5.03 percent , respectively ( P=0.02 ) ; spine,+2.12+/-4.06 and + 1.22+/-4.25 percent ( P=0.04 ) ; and total body , + 0.06+/-1.83 and -1.09+/-1.71 percent ( P calcium-vitamin D and placebo groups was significant at all skeletal sites after one year , but it was significant only for total-body bone mineral density in the second and third years . Of 37 subjects who had nonvertebral fractures , 26 were in the placebo group and 11 were in the calcium-vitamin D group ( P=0.02 ) . CONCLUSIONS In men and women 65 years of age or older who are living in the community , dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck , spine , and total body over the three-year study period and reduced the incidence of nonvertebral fractures", "BACKGROUND AND PURPOSE It has been demonstrated that bone mass was significantly reduced on the hemiplegic side of stroke patients , which might increase their risk of hip fracture . We evaluated the efficacy of 1 alpha-hydroxyvitamin D3 [ 1 alpha (OH)D3 ] and supplemental elemental calcium in maintaining bone mass and decreasing the incidence of hip fractures after hemiplegic stroke . METHODS In a r and omized study , 64 patients with hemiplegia after stroke with a mean duration of illness of 4.8 years received either 1 microgram 1 alpha (OH)D3 daily ( treatment group , n = 30 ) or an inactive placebo ( placebo group , n = 34 ) for 6 months and were observed for this duration . Both groups received 300 mg of elemental calcium daily . The bone mineral density ( BMD ) and metacarpal index ( MCI ) in the second metacarpals were determined by computed x-ray densitometry . The incidence of hip fractures in these patients was recorded . RESULTS BMD on the hemiplegic side decreased by 2.4 % in the treatment group and 8.9 % in the placebo group ( P = .0021 ) , while BMD on the intact side increased by 3.5 % and decreased by 6.3 % in the treated and placebo groups , respectively ( P = .0177 ) . In the treatment group , the difference in BMD between hemiplegic and nonhemiplegic sides decreased significantly compared with that before r and omization . This difference increased in the placebo group . We observed a similar improvement in MCI in the treatment group but not in the placebo group . Four patients in the placebo group suffered a hip fracture compared with none in the treatment group ( P = .0362 ) . CONCLUSIONS Treatment with 1 alpha (OH)D3 and supplemental elemental calcium can reduce the risk of hip fractures and can prevent further decreases in BMD and MCI on the hemiplegic side of patients with a long-st and ing stroke . Treatment also may improve these indices on the intact side", "Treatment with 1,25-(OH)2D3 ( calcitriol ) was compared with placebo in a double-blind , r and omized , parallel clinical trial of 24 months ' duration . Subjects were white women with postmenopausal osteoporosis . The study was completed by 15 patients who received placebo and 12 patients who received calcitriol . Positive slopes were observed in the active treatment group for total body calcium , bone mineral content of the radius , bone mineral density of the lumbar spine , and radiographic absorptiometry of the middle phalanges . In contrast , negative slopes were observed for the bone mineral measurements in the placebo group . Measurement of urinary hydroxyproline and of serum alkaline phosphatase and osteocalcin suggested that the mechanism of action of 1,25-(OH)2D3 involved reduction of bone resorption . Hypercalciuria occurred regularly and preceded hypercalcemia by about 2 weeks . A decline in creatinine clearance was observed in two patients , one of whom had nephrolithiasis on sonography . Calcitriol is effective in preventing bone loss , but must be used with caution", "Calcitriol was compared with placebo in the treatment of postmenopausal osteoporosis in a double-blind , r and omized , parallel clinical trial of 24 months ' duration . Adjustment was made in dietary calcium to maximize the dose of calcitriol . The study was completed by 15 patients who received placebo and 12 patients who received calcitriol . The calcitriol group had positive slopes ( compared with negative slopes for the placebo group ) for total body calcium , bone mineral content of the radius , bone mineral density of the lumbar spine , and radiographic absorptiometry of the middle phalanges . The difference between the two groups was statistically significant for each of these measurements . The fracture rate in the treatment group was 250 per 1,000 patient-years as compared with 333 for the placebo group . The mean dose of calcitriol was 0.8 micrograms per day . Hypercalcemia , hypercalciuria , and perhaps nephrolithiasis were observed as complications of treatment . Calcitriol increased bone mineral density by decreasing bone resorption , but not by increasing bone formation . Future studies should concentrate on treatment with oral calcitriol in lower doses . It would also be of interest to examine parenteral administration of calcitriol . It is possible that bone formation can be increased by achieving higher serum levels of the drug , whereas complications may be avoided by using a non-oral route of administration", "CONTEXT In humans , few studies have compared the potencies of ergocalciferol and cholecalciferol in improving and maintaining vitamin D status . OBJECTIVE Our objective was to evaluate the effects of a single very large dose of both calciferols on serum changes of 25-hydroxyvitamin D [ 25(OH)D ] , 1,25-dihydroxyvitamin D [ 1,25(OH)(2)D ] , ionized calcium , and parathyroid hormone ( PTH ) at baseline , and at 3 , 7 , 30 , and 60 d. DESIGN This was a prospect i ve r and omized intervention study . SETTING The study was performed in a nursing home residence . PARTICIPANTS A total of 32 elderly female patients ( age range 66 - 97 yr ) , with vitamin D deficiency was included in the study . INTERVENTION Participants were r and omized into four groups of eight to receive a single dose of 300,000 IU ergocalciferol or cholecalciferol by oral ( os ) or i m route . RESULTS 25(OH)D levels sharply increased at d 3 only when vitamins were given os . The 30-d basal difference in serum 25(OH)D was significantly greater after cholecalciferol os administration ( 47.8 + /- 7.3 ng/ml ) compared with other forms ( D(3 ) i m : 15.9 + /- 11.3 ; D(2 ) os : 17.3 + /- 4.7 ; D(2 ) i m : 5 + /- 4.4 ; all P area under the curve ( AUC ) of the serum 25(OH)D against time ( AUC(60 ) ) was : D(3 ) os , 3193 + /- 759 ng x d/ml vs. D(2 ) os , 1820 + /- 512 , P PTH levels at 3 ( P ( cholecalciferol ) significantly lowers PTH levels ( P = 0.037 ) . CONCLUSIONS Cholecalciferol is almost twice as potent as ergocalciferol in increasing serum 25(OH)D , when administered either by mouth or i m . 25(OH)D plays a role in modulating serum PTH", "BACKGROUND Elderly people who have a fracture are at high risk of another . Vitamin D and calcium supplements are often recommended for fracture prevention . We aim ed to assess whether vitamin D3 and calcium , either alone or in combination , were effective in prevention of secondary fractures . METHODS In a factorial- design trial , 5292 people aged 70 years or older ( 4481 [ 85 % ] of whom were women ) who were mobile before developing a low-trauma fracture were r and omly assigned 800 IU daily oral vitamin D3 , 1000 mg calcium , oral vitamin D3 ( 800 IU per day ) combined with calcium ( 1000 mg per day ) , or placebo . Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months . Analysis was by intention-to-treat and the primary outcome was new low-energy fractures . FINDINGS 698 ( 13 % ) of 5292 participants had a new low-trauma fracture , 183 ( 26 % ) of which were of the hip . The incidence of new , low-trauma fractures did not differ significantly between participants allocated calcium and those who were not ( 331 [ 12.6 % ] of 2617 vs 367 [ 13.7 % ] of 2675 ; hazard ratio ( HR ) 0.94 [ 95 % CI 0.81 - 1.09 ] ) ; between participants allocated vitamin D3 and those who were not ( 353 [ 13.3 % ] of 2649 vs 345 [ 13.1 % ] of 2643 ; 1.02 [ 0.88 - 1.19 ] ) ; or between those allocated combination treatment and those assigned placebo ( 165 [ 12.6 % ] of 1306 vs 179 [ 13.4 % ] of 1332 ; HR for interaction term 1.01 [ 0.75 - 1.36 ] ) . The groups did not differ in the incidence of all-new fractures , fractures confirmed by radiography , hip fractures , death , number of falls , or quality of life . By 24 months , 2886 ( 54.5 % ) of 5292 were still taking tablets , 451 ( 8.5 % ) had died , 58 ( 1.1 % ) had withdrawn , and 1897 ( 35.8 % ) had stopped taking tablets but were still providing data for at least the main outcomes . Compliance with tablets containing calcium was significantly lower ( difference : 9.4 % [ 95 % CI 6.6 - 12.2 ] ) , partly because of gastrointestinal symptoms . However , potentially serious adverse events were rare and did not differ between groups . INTERPRETATION The findings do not support routine oral supplementation with calcium and vitamin D3 , either alone or in combination , for the prevention of further fractures in previously mobile elderly people", " A cross-section of an elderly population was assessed in a double-blind trial for the effects of prophylactic vitamin D. The subjects who completed the trial were assessed clinical ly , by physiotherapy tests of muscle function and by biochemical analysis , before and after a course of vitamin D or placebo . A significant fall in serum phosphate was found in the placebo group but not in the vitamin D group . The fall was maximal between the months of October and March which correspond to maximum and minimum amounts of circulating 25-hydroxy-vitamin D during the year . No difference in muscle function between treated and untreated groups was shown . Two out of 63 individuals on vitamin D developed hypercalcaemia . It is concluded that , although there appears to be improvement in the phosphate status of treated patients over the short term of this trial , hypercalcaemia after vitamin D administration precludes the continuous prophylactic use of vitamin D at the levels employed in this trial", "OBJECTIVE The hypothesis was that the calcium and vitamin D supplementation prevents falls at the population level . STUDY DESIGN The OSTPRE-FPS was a r and omized population -based open-trial with 3-year follow-up . The supplementation group ( n=1566 ) received daily cholecalciferol 800IU+calcium carbonate 1000 mg , while the control group ( n=1573 ) received no supplementation or placebo . A r and omly selected sub sample of 593 subjects underwent a detailed measurement program including serum 25(OH)D measurements . MAIN OUTCOME MEASURE The occurrence of falls was the primary outcome of the study . The participants in the sub sample were telephoned at 4 months intervals and the rest of the trial population was interviewed by phone once a year . RESULTS In the entire trial population ( ETP ) , there were 812 women with 1832 falls in the intervention group and 833 women with 1944 falls in the control group ( risk ratio was 0.98 , 95 % CI 0.92 - 1.05 , P=0.160 ) . The supplementation was not associated with single or multiple falls in the ETP . However , in the sub sample , multiple fall incidence decreased by 30 % ( odds ratio ( OR ) 0.70 , 95 % CI 0.50 - 0.97 , P=0.034 ) in the supplementation group . Further , the supplementation decreased the incidence of multiple falls requiring medical attention ( OR 0.72 , 95 % CI 0.53 - 0.97 , P=0.031 ) in the ETP . The mean compliance in the entire trial population was 78 % and in the sub sample 79 % . DISCUSSION Overall , the primary analysis showed no association between calcium and vitamin D supplementation and risk of falls . However , the results of a post hoc analysis suggested that there was a decreased risk of multiple falls requiring medical attention : this finding requires confirmation", "OBJECTIVE Calcium and vitamin D deficiency is common in older individuals , particularly those who live in nursing homes , and increases the risk of osteoporosis and fractures . METHODS We conducted a r and omized double-blind placebo-controlled study of combined supplementation with 500 mg of elemental calcium , as carbonate , and 400 IU of vitamin D bid for 12 months in women older than 65 years of age with vitamin D deficiency , defined as serum 25(OH)D concentrations RESULTS Mean patient age was 75 + /- 7 years , and median daily dietary intakes of calcium and vitamin D were 697 mg and 66.8 IU in the supplemented group ( n = 95 ) and 671 mg and 61.8 IU in the placebo group ( n = 97 ) . The median serum 25(OH)D level was 7.0 ng/ml in both groups , and the medial intact parathyroid hormone ( PTHi ) levels were 49 and 48 pg/ml in the supplemented and placebo groups , respectively . The median increase in serum 25(OH)D was 22.0 ng/ml in the supplemented group and 4 ng/ml in the placebo group ( P median bone mineral density increase was significantly greater in the supplemented group than in the placebo group : + 2.98 % vs. -0.21 % at L2-L4 ( P = 0.0009 ) , + 1.19 % and -0.83 % at the femoral neck ( P = 0.015 ) , + 0.86 % and -0.56 % at the trochanter ( P = 0.015 ) , and + 0.99 % and + 0.11 % for the whole body ( P = 0.01 ) . Similarly , the median decrease in the main bone markers was significantly greater in the treated group than in the placebo group : -1.35 microg/l vs. + 0.50 microg/l for bone alkaline phosphatase ( P = 0.008 ) , -16.6 nmol/mmol creatinine vs. -2.3 nmol/mmol creatinine for urinary type I amino-terminal telopeptide ( P = 0.001 ) , and -896 pmol/l vs. -201 pmol/l for serum type I carboxy-terminal telopeptide ( P = 0.003 ) . We found no significant differences between the two groups for serum calcium , although urinary calcium excretion changed more in the supplemented group than in the placebo group . In conclusion , bone mass in older women with vitamin D deficiency increases significantly at the lumbar spine , femur , trochanter , and whole body after calcium and vitamin D supplementation for 1 year , and concomitantly bone markers improved as vitamin D levels returned to normal", "BACKGROUND A suboptimal vitamin D and calcium status has been associated with higher risk of type 2 diabetes in observational studies , but evidence from trials is lacking . OBJECTIVE We determined whether vitamin D supplementation , with or without calcium , improved glucose homeostasis in adults at high risk of diabetes . DESIGN Ninety-two adults were r and omly assigned in a 2-by-2 factorial- design , double-masked , placebo-controlled trial to receive either cholecalciferol ( 2000 IU once daily ) or calcium carbonate ( 400 mg twice daily ) for 16 wk . The primary outcome was the change in pancreatic β cell function as measured by the disposition index after an intravenous-glucose-tolerance test . Other outcomes were acute insulin response , insulin sensitivity , and measures of glycemia . RESULTS Participants had a mean age of 57 y , a body mass index ( BMI ; in kg/m(2 ) ) of 32 , and glycated hemoglobin ( Hb A(1c ) ) of 5.9 % . There was no significant vitamin D × calcium interaction on any outcomes . The disposition index increased in the vitamin D group and decreased in the no-vitamin D group ( adjusted mean change ± SE : 300 ± 130 compared with -126 ± 127 , respectively ; P = 0.011 ) , which was explained by an improvement in insulin secretion ( 62 ± 39 compared with -36 ± 37 mU · L(-1 ) · min , respectively ; P = 0.046 ) . Hb A(1c ) increased less , but nonsignificantly , in the vitamin D group than in the no-vitamin D group ( 0.06 ± 0.03 % compared with 0.14 ± 0.03 % , respectively ; P = 0.081 ) . There was no significant difference in any outcomes with calcium compared with no calcium . CONCLUSION In adults at risk of type 2 diabetes , short-term supplementation with cholecalciferol improved β cell function and had a marginal effect on attenuating the rise in Hb A(1c ) . This trial was registered at clinical trials.gov as NCT00436475", "BACKGROUND Serum 25-hydroxyvitamin D ( 25-[OH]D ) is considered the best biomarker of clinical vitamin D status . OBJECTIVE To determine the effect of increasing oral doses of vitamin D(3 ) on serum 25-(OH)D and serum parathyroid hormone ( PTH ) levels in postmenopausal white women with vitamin D insufficiency ( defined as a 25-[OH]D level ≤50 nmol/L ) in the presence of adequate calcium intake . These results can be used as a guide to estimate the Recommended Dietary Allowance ( RDA ) ( defined as meeting the needs of 97.5 % of the population ) for vitamin D(3 ) . DESIGN R and omized , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00472823 ) SETTING Creighton University Medical Center , Omaha , Nebraska . PARTICIPANTS 163 healthy postmenopausal white women with vitamin D insufficiency enrolled in the winter or spring of 2007 to 2008 and followed for 1 year . INTERVENTION Participants were r and omly assigned to receive placebo or vitamin D(3 ) , 400 , 800 , 1600 , 2400 , 3200 , 4000 , or 4800 IU once daily . Daily calcium supplements were provided to increase the total daily calcium intake to 1200 to 1400 mg . MEASUREMENTS The primary outcomes were 25-(OH)D and PTH levels at 6 and 12 months . RESULTS The mean baseline 25-(OH)D level was 39 nmol/L. The dose response was curvilinear and tended to plateau at approximately 112 nmol/L in patients receiving more than 3200 IU/d of vitamin D(3 ) . The RDA of vitamin D(3 ) to achieve a 25-(OH)D level greater than 50 nmol/L was 800 IU/d . A mixed-effects model predicted that 600 IU of vitamin D(3 ) daily could also meet this goal . Compared with participants with a normal body mass index ( 25-(OH)D level that was 17.8 nmol/L lower . Parathyroid hormone levels at 12 months decreased with an increasing dose of vitamin D(3 ) ( P = 0.012 ) . Depending on the criteria used , hypercalcemia occurred in 2.8 % to 9.0 % and hypercalciuria in 12.0 % to 33.0 % of participants ; events were unrelated to dose . LIMITATION Findings may not be generalizable to other age groups or persons with substantial comorbid conditions . CONCLUSION A vitamin D(3 ) dosage of 800 IU/d increased serum 25-(OH)D levels to greater than 50 nmol/L in 97.5 % of women ; however , a model predicted the same response with a vitamin D(3 ) dosage of 600 IU/d . These results can be used as a guide for the RDA of vitamin D(3 ) , but prospect i ve trials are needed to confirm the clinical significance of these results . PRIMARY FUNDING SOURCE National Institute on Aging", "The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials", "There are few data on the relative effects of calcium supplementation with or without extra vitamin D on BMD in patients selected for low vitamin D status . The aim of this study is to evaluate the relative importance of vitamin D and calcium treatment on BMD and bone-related chemistry in elderly women with vitamin D insufficiency . Three hundred two elderly women ( age , 77.2 + /- 4.6 yr ) with serum 25(OH)D concentrations in a 1-yr r and omized , double-blind , placebo-controlled trial . All subjects received 1000 mg calcium citrate per day with either 1000 IU ergocalciferol ( vitamin D(2 ) ) or identical placebo ( control ) . The effects of time and time treatment interactions were evaluated by repeated- measures ANOVA . At baseline , calcium intake was 1100 mg/d , and 25(OH)D was 44.3 + /- 12.9 nM ; this increased in the vitamin D group by 34 % but not the control group after 1 year ( 59.8 + /- 13.8 versus 45.0 + /- 13.3 nM , p Total hip and total body BMD increased significantly , and procollagen type I intact N-terminal propeptide ( PINP ) decreased during the study with no difference between the treatment groups ( hip BMD change : vitamin D , + 0.5 % ; control , + 0.2 % ; total body BMD change : vitamin D , + 0.4 % ; control , + 0.4 % ; PINP change : vitamin D , -3.9 % ; placebo , -2.8 % ) . Although the fasting plasma and urine calcium increased in both groups equally , there was no detectable change in serum PTH . The increase in 25(OH)D achieved with vitamin D supplementation had no extra effect on active fractional intestinal calcium absorption , which fell equally in both groups ( vitamin D , -17.4 % ; control , -14.8 % ) . In patients with a baseline calcium intake of 1100 mg/d and vitamin D insufficiency , vitamin D(2 ) 1000 IU for 1 year has no extra beneficial effect on bone structure , bone formation markers , or intestinal calcium absorption over an additional 1000 mg of calcium . Vitamin D supplementation adds no extra short-term skeletal benefit to calcium citrate supplementation even in women with vitamin D insufficiency" ]	41188c9a-06ff-11f0-808a-c43d1ab1c353
Early experiences in physical activity ( PA ) are important to shape healthy movement behaviours long-term ; as such , it is critical that PA is promoted from infancy , and that detrimental behaviours ( e.g. , prolonged sedentary time [ ST ] ) are minimized . The purpose of this systematic review and meta- analysis was to examine infants ’ and toddlers ’ movement behaviours across daytime hours . Seven online data bases were search ed for terms related to infants ( PA , ST , and accelerometry . Two independent review ers examined 4873 articles for peer- review ed original research , published in English , that assessed infants ’ ( counts/min ) and /or toddlers ’ PA or ST ( min/day ) using accelerometry across daytime hours . Infants ’ mean PA level ( counts/min ) was averaged across studies , and ranges were produced . Estimates of toddlers ’ movement behaviours were aggregated meta-analytically to produce average daily rates , and accelerometer placement , cut-point validity , device type , and epoch length were tested as a moderating variables . Twenty-four studies from 16 countries ( published 2011–2019 ) , representing 3699 participants , were included in the systematic review . Five studies reported on infants ’ PA , which ranged from 78.2 to 2580.5 cpm . Across 20 studies , toddlers ’ total PA , light PA , moderate-to vigorous-intensity PA , and ST ranged from 72.9 to 636.5 , 48.5 to 582.4 , 6.5 to 89.9 , and 172.7 to 545.0 min/day , respectively . After taking into account accelerometer placement , cut-point validity , device type , and epoch length , we found that toddlers engaged in 246.19 min/day ( SE = 28.50 ; 95 % CI : 190.34 , 302.04 ) of total PA , 194.10 min/day ( SE = 28.76 ; 95 % CI : 137.73 , 250.47 ) of light PA , and 60.16 min/day ( SE = 5.88 ; 95 % CI : 48.64 , 71.69 ) of moderate-to vigorous-intensity PA . Toddlers engaged in 337.04 min/day ( SE = 32.67 ; 95 % CI : 273.01 , 401.07 ) of ST . With limited studies conducted in infants ( n = 5 ) , PA estimates are inconclusive and largely heterogeneous . Overall , toddlers tend to exceed the total PA recommendation of 180 min/day ; however , very little of this time is spent at higher movement intensities . Even with high PA rates , toddlers still engage in substantial ST . More consistent and valid measurement protocol s are needed to improve comparability across studies	[ "Objective To assess the effect of a governmentally-led center based child care physical activity program ( Youp’là Bouge ) on child motor skills . Patients and methods We conducted a single blinded cluster r and omized controlled trial in 58 Swiss child care centers . Centers were r and omly selected and 1:1 assigned to a control or intervention group . The intervention lasted from September 2009 to June 2010 and included training of the educators , adaptation of the child care built environment , parental involvement and daily physical activity . Motor skill was the primary outcome and body mass index ( BMI ) , physical activity and quality of life secondary outcomes . The intervention implementation was also assessed . Results At baseline , 648 children present on the motor test day were included ( age 3.3 ± 0.6 , BMI 16.3 ± 1.3 kg/m2 , 13.2 % overweight , 49 % girls ) and 313 received the intervention . Relative to children in the control group ( n = 201 ) , children in the intervention group ( n = 187 ) showed no significant increase in motor skills ( delta of mean change ( 95 % confidence interval : -0.2 ( −0.8 to 0.3 ) , p = 0.43 ) or in any of the secondary outcomes . Not all child care centers implemented all the intervention components . Within the intervention group , several predictors were positively associated with trial outcomes : 1 ) free-access to a movement space and parental information session for motor skills 2 ) highly motivated and trained educators for BMI 3 ) free-access to a movement space and purchase of mobile equipment for physical activity ( all p child care centers confirms the complexity of implementing an intervention outside a study setting and identified potentially relevant predictors that could improve future programs . Trial registration Clinical trials.gov", "Physical activity is beneficial for children ’s well-being . The effect of dietary supplementation on children ’s physical activity in food-insecure areas remains little studied . We examined the effects of a lipid-based nutrient supplement ( LNS ) on children ’s objective ly measured physical activity in a r and omised , controlled , outcome -assessor-blinded trial . Mothers of the children received one capsule daily of Fe-folic acid ( IFA ) , one capsule containing eighteen micronutrients ( MMN ) or one 20 g sachet of LNS ( containing twenty-two MMN , protein , carbohydrates , essential fatty acids and 494 kJ ( 118 kcal ) ) during pregnancy and for 6 months thereafter . Children in the IFA and MMN groups received no supplementation , and these groups were collapsed into a single control group ; children in the LNS group received 20 g LNS from 6 to 18 months . We measured physical activity with accelerometers over 1 week at 18 months . The main outcome was mean vector magnitude counts/15 s. Of the 728 children at the beginning of child intervention at 6 months , 570 ( 78 % ) provided sufficient data for analysis . The mean accelerometer counts for the 190 children in the LNS group and for the 380 children in the control group were 303 ( sd 59 ) and 301 ( sd 56 ) , respectively ( P for difference=0·65 ) . LNS , given to mothers during pregnancy and 6 months postpartum and to their infants from 6 to 18 months of age , did not increase physical activity among 18-month-old children", "IMPORTANCE Identifying associations between preschool-aged children 's electronic media use and their later well-being is essential to supporting positive long-term outcomes . OBJECTIVE To investigate possible dose-response associations of young children 's electronic media use with their later well-being . DESIGN , SETTING , AND PARTICIPANTS The IDEFICS ( Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants ) study is a prospect i ve cohort study with an intervention component . Data were collected at baseline from September 1 , 2007 , through June 30 , 2008 , and at follow-up from September 1 , 2009 , through May 31 , 2010 , in 8 European countries participating in the IDEFICS study . This investigation is based on 3604 children aged 2 to 6 years who participated in the longitudinal component of the IDEFICS study only and not in the intervention . EXPOSURE Early childhood electronic media use . MAIN OUTCOMES AND MEASURES The following 6 indicators of well-being from 2 vali date d instruments were used as outcomes at follow-up : Peer problems and Emotional problems subscales from the Strengths and Difficulties Question naire and Emotional well-being , Self-esteem , Family functioning , and Social networks subscales from the KINDLR ( Question naire for Measuring Health-Related Quality of Life in Children and Adolescents-Revised Version ) . Each scale was dichotomized to identify those children at risk for poorer outcomes . Indicators of electronic media use ( weekday and weekend television and electronic game [e-game]/computer use ) from baseline were used as predictors . RESULTS Associations varied between boys and girls ; however , associations suggested that increased levels of electronic media use predicted poorer well-being outcomes . Television viewing on weekdays or weekends was more consistently associated with poorer outcomes than e-game/computer use . Across associations , the likelihood of adverse outcomes in children ranged from a 1.2- to 2.0-fold increase for emotional problems and poorer family functioning for each additional hour of television viewing or e-game/computer use depending on the outcome examined . CONCLUSIONS AND RELEVANCE Higher levels of early childhood electronic media use are associated with children being at risk for poorer outcomes with some indicators of well-being . Further research is required to identify potential mechanisms", "Background : Recent studies have cl aim ed a positive effect of physical activity and body composition on vagal tone . In pediatric population s , there is a pronounced decrease in heart rate with age . While this decrease is often interpreted as an age-related increase in vagal tone , there is some evidence that it may be related to a decrease in intrinsic heart rate . This factor has not been taken into account in most previous studies . The aim of the present study was to assess the association between physical activity and /or body composition and heart rate variability ( HRV ) independently of the decline in heart rate in young children . Methods : Anthropometric measurements were taken in 309 children aged 2–6 years . Ambulatory electrocardiograms were collected over 14–18 h comprising a full night and accelerometry over 7 days . HRV was determined of three different night segments : ( 1 ) over 5 min during deep sleep identified automatically based on HRV characteristics ; ( 2 ) during a 20 min segment starting 15 min after sleep onset ; ( 3 ) over a 4-h segment between midnight and 4 a.m. Linear models were computed for HRV parameters with anthropometric and physical activity variables adjusted for heart rate and other confounding variables ( e.g. , age for physical activity models ) . Results : We found a decline in heart rate with increasing physical activity and decreasing skinfold thickness . HRV parameters decreased with increasing age , height , and weight in HR-adjusted regression models . These relationships were only found in segments of deep sleep detected automatically based on HRV or manually 15 min after sleep onset , but not in the 4-h segment with r and om sleep phases . Conclusions : Contrary to most previous studies , we found no increase of st and ard HRV parameters with age , however , when adjusted for heart rate , there was a significant decrease of HRV parameters with increasing age . Without knowing intrinsic heart rate correct interpretation of HRV in growing children is impossible", "OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity", "The purpose of this study was twofold : first to document the gender differences in Moderate to Vigorous Physical Activity ( MVPA ) according to two epoch systems ( 5 vs. 60 s ) in preschoolers , and , second to document the differences in physical activity ( PA ) patterns according to two different epoch choices . The sample comprised 59 preschoolers ( 31 girls ) aged 2 - 5 years old . PA was assessed by accelerometer during school hours . The time spent in MVPA was significantly higher ( p MVPA . Different epoch times might affect the time spent in MVPA among preschool children", "Adequate physical activity is associated with improved sleep in adults . Such associations , however , vary greatly across studies in pediatric population s , with no studies involving infants found in the literature . This prospect i ve observational study was design ed , therefore , to examine the association between physical activity and sleep patterns in infants . A total of 183 healthy infants aged 6 months wore an actigraph for 7 days to measure physical activity and sleep . Parents and caregivers completed a sleep-activity diary over the same period documenting the different types of infant activities . Daily mean time spent in screen-time-or-limited physical activity , including screen-based ( e.g. , watching television or other electronic devices ) and non-screen based activity ( e.g. , quiet play or restricted infant movement when carried by caregivers or seated in high chairs , swings , or bouncer seats ) , was 6.68 hr ( SD = 1.99 ) , which represented 47.50 % of daytime waking hours ( SD = 13.73 ) . We found that 65 ( 35.5 % ) infants engaged in some screen time during the study , with 10 ( 5.5 % ) infants having an average daily screen time > 30 min . In our multivariate linear regression model , more hours of screen-time-or-limited physical activity per day were significantly associated with a decrease in total daily 24 hr sleep duration ( p reducing screen-time-or-limited physical activity might be an approach for promoting adequate sleep and lengthening infant daily sleep duration" ]	41188cd6-06ff-11f0-808a-c43d1ab1c353
Group sports interventions have been developed to improve health-related physical fitness of overweight/obese youth . However , its benefits are not systematic ally documented . This study synthesizes the evidence about the effects of group sports on health-related physical fitness of overweight/obese youth . Pubmed , Web of Knowledge , Scopus , Medline , CINAHL , SportD iscus , and Academic Search Complete were search ed in February 2016 . Studies assessing the effects of group sports on body composition , cardiorespiratory endurance , muscle strength , flexibility , and neuromotor fitness of overweight/obese youth ( aged Effect sizes ( ES ) were calculated with Cohen 's d and its 95 % confidence intervals ( CI ) . Improvements were found in ( i ) body composition - percentage of fat body mass ( pooled ES = 0.67 ; 95 % CI = 0.24 - 1.10 ) and waist circumference ( ES = 0.69 ; P = 0.004 ) ; ( ii ) cardiorespiratory endurance - peak oxygen consumption ( pooled ES = 0.53 ; 95 % CI = 0.13 - 0.92 ) and ( iii ) muscle strength - h and grip strength ( ES = 0.72 ; P = 0.003 ) . No significant effects were found for body mass index ( pooled ES = 0.27 ; 95 % CI = -0.14 to 0.69 ) , percentage of lean body mass ( ES = 0.01 ; P > 0.05 ) , maximal power output ( ES from 0 to 0.06 ; P > 0.05 ) , sit- and -reach test ( pooled ES = 0.26 ; 95 % CI = -0.16 to 0.68 ) and agility test ( ES = 0 ; P = 0.48 ) . Group sports improve body composition , cardiorespiratory endurance , and h and grip strength of overweight/obese youth . Flexibility and neuromotor fitness do not seem to change following group sports	[ "OBJECTIVE To evaluate the feasibility , acceptability , and efficacy of an after-school team sports program for reducing weight gain in low-income overweight children . DESIGN Six-month , 2-arm , parallel-group , pilot r and omized controlled trial . SETTING Low-income , racial/ethnic minority community . PARTICIPANTS Twenty-one children in grade s 4 and 5 with a body mass index at or above the 85th percentile . INTERVENTIONS The treatment intervention consisted of an after-school soccer program . The \" active placebo \" control intervention consisted of an after-school health education program . MAIN OUTCOME MEASURES Implementation , acceptability , body mass index , physical activity measured using accelerometers , reported television and other screen time , self-esteem , depressive symptoms , and weight concerns . RESULTS All 21 children completed the study . Compared with children receiving health education , children in the soccer group had significant decreases in body mass index z scores at 3 and 6 months and significant increases in total daily , moderate , and vigorous physical activity at 3 months . CONCLUSION An after-school team soccer program for overweight children can be a feasible , acceptable , and efficacious intervention for weight control", "The present study aim ed at analyzing the efficacy of a 6-month football training program compared with a st and ard exercise program on health and fitness parameters in overweight children . The study design was a 6-month , two-arm , parallel-group r and omized trial . Twenty-two overweight children were r and omly assigned to two groups ( age=10.8+/-1.2 years , height=1.56+/-0.08 m , weight= 65.1+/-11.4 kg ) . One group conducted a football training program , and the other group an established st and ard sports program . Both interventions took place three times per week from mid-May to mid-November . Before , after 3 months and after the training period , comprehensive testing was conducted : anthropometric characteristics , cycling ergometry , psychometric monitoring as well as several motor ability tests . Maximal performance capacity increased and submaximal heart rate during cycling ergometry decreased significantly . Several motor skills as well as self-esteem also improved considerably . Body composition and other psychometric variables remained nearly unchanged . No relevant differences were observed between both exercise programs . It can be concluded that a 6-month football training is as efficacious in improving the physical capacity , health-related fitness parameters and self-esteem of overweight children as a st and ard exercise program . These results provide further evidence that playing football has significant health effects", "Background . Obesity has become the most common pediatric chronic disease in the modern era . Early prevention and treatment of childhood and adolescent obesity is m and ated . Surprisingly , however , only a minor fraction of obese children participate in weight reduction interventions , and the longer-term effects of these weight-reduction interventions among children have not been eluci date d. Objective . To examine prospect ively the short- and long-term effects of a 3-month , combined dietary-behavioral-physical activity intervention on anthropometric measures , body composition , dietary and leisure-time habits , fitness , and lipid profiles among obese children . Methods . In this r and omized prospect i ve study , 24 obese subjects completed the 3-month intervention and were compared with 22 obese , age- and gender-matched , control subjects . Results . At 3 months , there were significant differences in changes in body weight ( −2.8 ± 2.3 kg vs 1.2 ± 2.2 kg ) , BMI ( −1.7 ± 1.1 kg/m2 vs −0.2 ± 1.0 kg/m2 ) , body fat percentage ( from skinfold tests ; −3.3 ± 2.6 % vs 1.4 ± 4.7 % ) , serum total cholesterol level ( −24.6 ± 15.1 mg/dL vs 0.8 ± 18.7 mg/dL ) , low-density lipoprotein cholesterol level ( −23.3 ± 15.2 mg/dL vs −3.7 ± 17.3 mg/dL ) , and fitness ( 215 ± 107 seconds vs 50 ± 116 seconds ) in the intervention group versus the control group . After a 1-year follow-up period , there were significant differences between the intervention group ( n = 20 ) and the control group ( n = 20 ) in body weight ( 0.6 ± 6.0 kg vs 5.3 ± 2.7 kg ) , BMI ( −1.7 ± 2.3 kg/m2 vs 0.6 ± 0.9 kg/m2 ) , and body fat percentage . There was a significant increase in leisure-time physical activity among the intervention participants , compared with a decrease among the control subjects . Conclusions . Our data demonstrate the short- and longer-term beneficial effects of a combined dietary-behavioral-physical activity intervention among obese children . These results highlight the importance of multidisciplinary programs for the treatment of childhood obesity and emphasize their encouraging long-term effects", "BACKGROUND : The Freiburg Intervention Trial for Obese Children ( FITOC ) is an interdisciplinary , outpatient program for obese children consisting of regular physical exercise and comprehensive dietary and behavioral education . Parental involvement is required . The study is design ed as a longitudinal , nonr and omized clinical observation study . An 8-month intensive phase preceded a follow-up phase of 1 y or longer . METHODS : Data were collected from 31 groups comprising 496 children ( 267 girls , 229 boys ) , with an average age of 10.5 y. Body height and weight , fasting total-cholesterol ( CH ) , low-density lipoprotein-cholesterol ( LDL-C ) , high-density lipoprotein-cholesterol ( HDL-C ) and physical performance were measured initially and after 8.5 months . A group of n=35 obese children ( 16 girls , 19 boys ) who did not take part in this intervention program served as controls . RESULTS : After the intensive intervention phase , body mass index ( BMI , kg/m2 ) as well as BMI deviation scores ( BMI -SDS ) decreased in both sexes ( P BMI increased ( P BMI -SDS remained constant . Whereas CH was only significantly lower ( P LDL-C decreased significantly in both sexes . HDL-C tended to increase in both sexes ( not significant ) . The controls showed no significant changes in CH , LDL-C and HDL-C. The fitness levels ( W/kg body weight ) improved in the intervention group ( P obese children can be successfully treated in such an intervention program . BMI -SDS and risk factors decreased and physical performance improved . To maintain therapeutical success , we highly recommended that these children enroll in community-based exercise programs in order to help them maintain a more active lifestyle after the follow-up phase", "Abstract We examined effects of a 3-month football training programme in overweight children using comprehensive echocardiography and peripheral arterial tonometry . Twenty preadolescent overweight children ( 17 boys , 3 girls aged 8–12 yrs ; body mass index [ BMI ] ≥ 85th percentile ) participated in a structured 3-month football training programme , consisting of 4 weekly 60–90 min sessions with mean heart rate ( HR ) > 80 % of HRmax ( football group , FG ) . A parallel control group ( CG ) included 11 children ( 7 boys , 4 girls ) of equivalent age from an obesity clinic . After 3 months , systolic blood pressure was unchanged in FG , but had increased in CG ( 112 [ s 6 ] vs. 122 [ 10 ] mmHg , P = 0.02 ) . FG demonstrated increased left ventricular ( LV ) posterior wall diameter ( 0.60 [ 0.07 ] vs. 0.68 [ 0.10 ] cm , P an improved right ventricular systolic function determined by tricuspid annular plane systolic excursion ( TAPSE , 2.01 [ 0.29 ] vs. 2.27 [ 0.28 ] cm , P = 0.003 ) . Measures of LV systolic function showed only discrete alterations and two-dimensional ( 2D ) global strain was not changed . After 3 months , global isovolumetric relaxation time ( IVRTglobal ) had increased in FG ( 64.0 [ 7.5 ] vs. 73.9 [ 9.4 ] ms , P examined LV diastolic function variables were not altered . No echocardiographic changes were observed in CG . Between-group differences in pre-post delta values were observed for systolic blood pressure , TAPSE , and IVRTglobal ( P = 0.02–0.03 ) . We conclude that short-term football training may have positive structural and functional effects on the cardiovascular system in overweight preadolescent children", "Little is known about the relative injury risk of obese adolescent football players . Two high school varsity teams were followed prospect ively for injuries after measurement of height , weight , and triceps and subscapular skinfolds during the preseason . Certified athletic trainers who were present at all practice s recorded all injuries that required a player to miss at least one practice or game . In all , 98 players were enrolled in the study . Twenty-eight injuries were documented in 24 different players . There were 27 ( 28 % ) players with the sum of skinfolds > or = 95th percentile for age ; eight of them had nine injuries . The overall prevalence of injuries per player per season was 0.28 for players High body mass ( body weight > 90 kg ) was associated with a 2.5 times higher relative risk of injury . While this study did not find evidence for an overall higher injury rate in overly fat high school football players , an alarmingly high incidence of obesity was found in this athletic population", "The effects of a 5-month intervention of football instruction and practice on the perceived psychological status and body composition of overweight boys were examined . Twelve boys ( 8 - 12 years ; body mass index ≥ 85th percentile ) participated in a structured 5-month football program , consisting of four weekly 60 - 90 min sessions with mean heart rate > 80%HRmax [ football group ( FG ) ] . A control group ( CG ) included eight boys of equivalent age from an obesity clinic located in the same area as the school . Both groups participated in two sessions of 45 - 90-min physical education per week at school . Indicators of perceived psychological status included body image , self-esteem , attraction to participation in physical activity , and perceived physical competence measured with st and ardized question naires . Body composition was evaluated using dual-energy X-ray absorptiometry . From baseline through 5 months , FG improved ( P all indicators of psychological status ( % Δ = + 11.7 to + 29.2 % ) compared with CG ( % Δ = -32.1 to + 0.5 % ) . Changes in percentage body fat and lean body mass , however , did not differ between FG and CG . The findings suggest that a 5-month football intervention program was effective in improving the psychological status of overweight boys but did not significantly alter body composition" ]	41188d12-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Very high blood pressure during pregnancy poses a serious threat to women and their babies . The use of drugs to lower blood pressure will reduce this risk for the women , and possibly also for the baby . OBJECTIVES The objective of this review was to compare different antihypertensive drugs used for treatment of severe hypertension during pregnancy . SEARCH STRATEGY We search ed the Cochrane Pregnancy and Childbirth Group trials register ( April 2002 ) , the Cochrane Controlled Trials Register ( The Cochrane Library , Issue 2 2002 ) and MEDLINE ( April 2002 ) . SELECTION CRITERIA Studies were r and omised trials . Quasi r and om design s were excluded . Participants were women with severe hypertension during pregnancy . Women postpartum at trial entry were excluded . Interventions were any comparisons of one antihypertensive agent with another . DATA COLLECTION AND ANALYSIS Data were extracted independently by two review ers to assess eligibility and describe the trial characteristics , and by one review er for the meta-analyses . Discrepancies were resolved by discussion . There was no blinding of authors hip or results . Whenever possible , unpublished data were sought from investigators . MAIN RESULTS Twenty trials were included ( 1637 women ) and 19 were excluded . There were ten different comparisons . Hydralazine was the most common drug for others to be evaluated against . Diazoxide , given as 75 mg bolus injections , appears to be associated with maternal hypotension requiring treatment , and ketanserin is less effective than hydralazine at reducing blood pressure . There is no other clear evidence that any one of the other antihypertensive agents is better than another for women with severe hypertension during pregnancy . REVIEW ER 'S CONCLUSIONS Until better evidence is available , the choice of antihypertensive should depend on the experience and familiarity of an individual clinician with a particular drug , and on what is known about adverse maternal and fetal side-effects . Exceptions are diazoxide and ketanserin , which are probably not good choices	[ "The effect of intravenous infusion of labetalol and of dihydralazine in increasing doses was compared in 12 women with severe hypertension in pregnancy . In 5 our of 6 women labetalol produced a smooth , progressive fall in blood pressure to normal levels with minimal side effects . In 2 our of 6 women on dihydralazine the blood pressure control was satisfactory but in the remaining 4 patients treatment had to by discontinued because of unpredictable , sudden falls in blood pressure . One of the 6 infants of mothers treated with labetalol manifested signs of adrenergic blockade . Continuous infusion of labetalol appears to offer significant advantages in the management of severe hypertension in pregnancy and merits further trial", "Summary : The results of a prospect i ve trial to evaluate the use of diazoxide and labetalol given intravenously in the management of severe hypertensive disease in pregnancy are presented", "OBJECTIVES The purpose s of this study were to compare the efficacy of sublingual nifedipine with intravenous hydrallazine in the control of acute hypertension of pregnancy and to make a preliminary assessment whether sublingual nifedipine could be recommended for use by midwives faced with severe hypertension in pregnancy in a rural setting . METHODS Subjects were 200 consecutive patients admitted to Kuala Tereng-ganu General Hospital , Malaysia with severe hypertension in pregnancy between August 1989 and June 1990 . Admission criteria were an ongoing viable pregnancy more than 28 weeks and diastolic blood pressure ( DBP ) more than 120 mmHg . The patients were r and omly divided into 2 groups . In group I , sublingual nifedipine 5 mg was administered and repeated after 15 minutes if DBP > 120 mmHg ; and in group II hydrallazine 5 mg was intravenously injected and repeated after 15 minutes if DBP > 120 mmHg . Both groups were put on hydrallazine infusion if DBP > 120 mmHg after 30 minutes . The Chi-square test was used for analysis with significance at p efficacy of therapy for decreasing blood pressure between the 2 groups . The groups were comparable by age , parity , gestational age at presentation , birth weight of infants , incidence of postpartum haemorrhage and fetal distress . Caesarian section rates were similar . In the observational studies on nurses administering the drugs , no significant difficulties were observed . CONCLUSION Sublingual nifedipine was comparable to IV hydrallazine in the treatment of acute hypertension of pregnancy . Nurses were able to administer lingual nifedipine without difficulty", "OBJECTIVE The purpose of this study was to compare the efficacy of nifedipine ( Cordipin ) and hydralazine in lowering blood pressure in severe preeclampsia . METHOD A r and omized , prospect i ve study of 104 patients with severe preeclampsia in the Department of Obstetrics and Gynecology , Korle-Bu Teaching Hospital , Accra , Ghana , was conducted between January 1992 and June 1994 . RESULTS Of the 104 patients recruited into the study , six did not deliver at our hospital and were thus excluded from the study . Nifedipine and hydralazine as first-line drugs controlled the blood pressure in 44 and 35 patients , respectively , but failed in 5 and 14 , respectively . This was statistically significant ( P mean birth weight was higher in the nifedipine group ( 2500+/-800 g vs. 2400+/-800 g ) . There were 11 admissions to the neonatal intensive care unit in the nifedipine group and 13 in the hydralazine group but the difference was not statistically significant . CONCLUSION Nifedipine and hydralazine could both be used effectively to control blood pressure in severe preeclampsia in our subregion . While hydralazine is administered intravenously and needs strict monitoring , nifedipine is more effective , is easy to administer orally , less dem and ing on hospital staff , convenient and more predictable", "Pre-eclampsia is an extremely severe condition . It is associated with vasospasm , activation of the coagulation system and abnormal haemostasis . In pre-eclamptic patients increased plasmatic concentrations of fibronectin , laminin , von Willebr and factor ( VWF ) and endothelin are observed . Experimental studies on rats have also shown that the doses of antithrombin III ( AT ) needed to mediate anti-inflammatory processes are much higher than those required to obtain the anti-coagulant effect . The study aim ed to evaluate the clinical efficacy of treatment with high AT doses ( HD ) in comparison with st and ard doses ( SD ) . The primary endpoint was the prolongation of pregnancy defined as time ( in days ) from enrollment to delivery and to assess the maternal bleeding at and after delivery . The secondary endpoint was to demonstrate a role for AT in controlling haemostasis at conventional doses , and the inflammatory state at higher doses . The biochemical parameters assessed were : AT activity ( % ) , Fibronectin ( Fn ) , Fibrinogen , D-dimer , Uricemia , Proteinuria 24h , Protein C Reactive ( PCR ) , Granulocyte Elastase and Endothelin . This study included 23 pre-eclamptic women . Patients were r and omly subdivided into two groups : 10 patients ( \" cases \" ) were treated with high doses of AT ( 6 vials : 3000 units ) once daily for 5 days , or until delivery , while 13 women ( \" controls \" ) were treated with doses of AT sufficient to maintain at least 80 % of the activity . High-dose therapy was associated with prolongation of pregnancy by 2.5 days more when compared with controls ( p = 0.03 ; Mann-Whitney test ) . The incidence of clinical significant bleeding was lower in cases than in controls ( mean 550 mL vs. 650 mL , respectively ) . Preventive- and conservative-type treatment of moderate-severe pre-eclampsia , based on the administration high doses of AT , allows a significant prolongation of pregnancy , and thus a better neonatal outcome , as well as less maternal intra- and post-operative bleeding . Fn , PCR and elastase levels ( markers of inflammation ) decrease in the HD group in comparison with SD group . In the HD group , the AT plasma levels were obviously higher both at the end of the treatment ( p fibrinogen and D-dimer levels were above the reference interval in both groups . TPA and PAI 1 were found to be significantly raised in the course of pre-eclampsia . In conclusion , the bio-chemical findings support a role for AT in controlling the haemostasis at conventional doses , and the inflammatory state at higher doses", "OBJECTIVE To evaluate the safety of long-term nicardipine treatment in severely pre-eclamptic women and their fetuses/newborns . METHODS We divided 50 pregnant women into three groups according to the length of their treatment : short-term treatment of severely pre-eclamptic women ( 7 days or less , n=20 ) ; medium-term treatment also of severely pre-eclamptic women ( 8 - 28 days , n=20 ) ; and long-term treatment of women with severe superimposed pre-eclampsia ( 29 days or more , n=10 ) . RESULTS Nicardipine significantly lowered both systolic ( P diastolic blood pressures ( P incidence of delivery before 28 weeks of gestation was very low in all three groups . There were no maternal or fetal/neonatal adverse effects . CONCLUSION Our results suggest that long-term treatment with nicardipine for severe pre-eclampsia is as effective and safe as a short- and medium-term treatment", "The administration of diazoxide to patients with severe hypertension in pregnancy in 60 and 150 mg doses , which are smaller than the usual 300 mg dose , is described . A 60 mg dose is effective and does not cause the undesirable hypotension occasionally produced by larger doses", "We hypothesised that long term epidural anaesthesia suppresses sympathetic overactivity in pre-eclampsia . Two equal groups of severe pre-eclamptic patients were treated either with long-term epidural anaesthesia ( epidural group ) or bed rest , diet control , and an antihypertensive drug ( control group ) . After 7 days of epidural block , mean arterial blood pressures decreased , platelet count and serum total protein increased in all cases while proteinuria decreased in four cases . All patients treated with a long-term epidural therapy continued their pregnancies for more than 3 weeks after admission . The infants in the epidural group had 1-min Apgar scores above 8 , a body weight of 2240 ± 310 g ( mean ± s.d . ) and normal neonatal progress . In contrast , the pregnancies of eight patients in the control group were terminated within 2 weeks of admission due to severe pre-eclampsia or foetal distress , the birth weight of the infants was 1590 ± 380 g ( mean ± s.d . ) and four had neonatal distress . Progressive worsening in the mean arterial pressure , proteinuria , platelet count and serum total protein was found in these patients . Long-term epidural anaesthesia suppresses the sympathetic hyperactivity and thus improves pre-eclamptic condition which may open a new treatment in case of progressive severe pre-eclampsia", "This prospect i ve study was conducted at Dhaka Medical College and Hospital , Bangladesh . The objective was to identify the time required to control high blood pressure levels in obstetric patients by injection of hydralazine in a bolus intravenous dose vs continuous drip . Seventy-seven patients with eclampsia and hypertensive emergencies comprised the target population . Patients were managed either by hydralazine drip in normal saline ( existing official protocol , n = 33 ) or hydralazine bolus injection ( as experiment , n = 44 ) until diastolic blood pressure fell to 90 - 95 mmHg . Results were compared . Student 's t-test was done for statistical significance , and a P value of The groups were similar with respect to maternal age and their mean systolic and diastolic blood pressure at the time of enrollment . Patients who received bolus injection required less time to achieve the therapeutic goal ( 65.23 + /- 23.38 minutes ) than continuous drip ( 186.36 + /- 79.77 minutes ; P lower doses ( 6.68 + /- 1.66 mg ) in comparison to that required by control group ( 20.07 + /- 11.38 mg ; P overshoot hypotension in either group . The data suggest that hydralazine bolus dose is equally safe and more effective than continuous drip in the management of hypertensive emergencies in pregnancy", "BACKGROUND The primary objective of treatment in women with severe hypertension and pre-eclampsia is to prevent complications such as encephalopathy and haemorrhage . In many countries dihydralazine is considered the drug of choice for treating hypertension in pregnancy , because it now has been used safely for about 30 years , and the introduction of a new drug in pregnancy is a difficult task with partially unknown hazards . In some other countries combined alpha- and beta-blockers are also used . Taking into account that some patients with pre-eclampsia do not respond to dihydralazine and the drug has serious side-effects like headache and reflex tachycardia , there is some need for developing alternative treatment strategies using drugs that are more adequate for pregnancy than dihydralazine . METHODS Urapidil is a post-synaptic alpha 1 adrenoceptor antagonist , which is widely used to control hypertensive crises unrelated to pregnancy . Since it is known that pre-eclampsia is associated with increased sympathetic activity , administration of an alpha 1 adrenoceptor antagonist provides a reasonable therapeutic basis . So far there is only one report describing the i.v . use of urapidil in the treatment of hypertension in pregnancy unresponsive to dihydralazine and one report which describes the oral use of urapidil . In an earlier pilot study we examined the dose range for i.v . application of urapidil necessary for adequate blood pressure control in patients with pre-eclampsia . In the present r and omized controlled study 26 white women with pre-eclampsia and hypertension in pregnancy were included . Treatment was not blinded . During the initial period of intensive intravenous treatment all subjects were under constant surveillance by a physician and a nurse . RESULTS Effective prolonged control of blood pressure ( values below 150/100 mmHg ) was achieved in all patients of the two groups . In one patient of the dihydralazine group signs of lightheadedness and near syncope were noted . After this side-effect of dihydralazine the patient was treated with urapidil . At the end of the observation period the maternal heart rate in the dihydralazine group was higher than in the urapidil group . CONCLUSIONS Since urapidil decreased the high blood pressure in patients with pre-eclampsia without serious side-effects urapidil appears preferable superior to dihydralazine . The haemodynamic effects of urapidil were more predictable than those of dihydralazine . The reduction of intracerebral pressure could be an additional advantage of urapidil in the treatment of patients with pre-eclampsia", "OBJECTIVE A hypothesis , based on animal studies and human observational studies , was developed proposing a direct pathogenic link between hyperuricemia and preeclampsia . Epidemiological characteristics of preeclampsia such as its uniqueness to humans and an increased incidence of preeclampsia in multiple pregnancies , increased body mass index , renal and hypertensive disease all have uric acid as their common denominator . Animal studies have linked hyperuricaemia to hypertensive , cardiovascular and renal disease . The aim of the study was to determine whether lowering the serum uric acid levels in preeclampsia would affect biochemical parameters and hypertensive control . DESIGN A r and omized , double-blind , placebo controlled study . SETTING A tertiary referral center . POPULATION Forty women with preeclampsia between 26 and 32 weeks gestation . INTERVENTION Probenecid 250 mg twice daily for seven days . MAIN OUTCOME MEASURES Renal function and haematological parameters , hypertensive control . RESULTS In the Probenecid group , there was a significant drop in the serum uric acid levels . Lower uric acid levels in the Probenecid group had no significant effect on blood pressure . Patients in the Probenecid group had a significantly lower serum creatinine value at the end of the study when compared to patients in the placebo group . Other renal function parameters ( creatinine clearance , urea , 24 h urinary protein excretion ) did not show any significant difference between the two groups . Platelet count differed between the two groups with the platelet count being significantly higher in the Probenecid group at the end of the study . CONCLUSION The significant improvement in the platelet count in the Probenecid group warrants further study", "A double-blind , r and omized , placebo-controlled trial was conducted to evaluate whether treatment with Antithrombin ( AT ) concentrates improved the clinical and perinatal outcome in patients with severe preeclampsia . Severe preeclamptic patients ( 24 to 35 weeks of gestation . Gestosis Index ( GI ) > or = 6 points ) were r and omized into two groups : 66 received AT and 67 received placebo . There were no statistical differences in the clinical profiles of the two groups . Study drugs were given intravenously once daily for 7 consecutive days . Maternal symptoms were evaluated from the difference of GI between before and after treatment , and fetal findings were evaluated from the changes of the biophysical profile score and the estimated fetal weight gain . Improvement was significantly greater in the AT group for both the GI ( p = 0.020 ) and the estimated fetal weight gain ( p = 0.029 ) . The improvement of coagulation parameters was also evaluated . The D-dimer levels increased significantly in the placebo group ( p = 0.026 ) , but did not change in the AT group . Gestation was significantly prolonged ( p = 0.007 ) , and the number of low-birth weight infants was significantly smaller ( p = 0.011 ) in the AT group . No adverse events related to AT were observed . It is revealed that AT concentrate therapy for preeclampsia is effective and safe , leading to an improved perinatal outcome", "The effect of nifedipine ( Adalat ; Bayer-Miles)--a calcium channel blocker , which has a well-established place in nonobstetric hypertension -- was compared with dihydralazine in 33 primigravidas with severe hypertension of pregnancy . Patients with a diastolic blood pressure greater than 110 mmHg before drug administration were r and omly assigned to treatment with either nifedipine or dihydralazine . Both drugs were found to be equally efficacious . Nifedipine , however , showed an earlier onset of action in lowering systolic blood pressure and had the advantage of oral administration", "Summary . Intravenous treatment with 10 mg of hydralazine or 100 mg of labetalol was r and omly allocated to 30 hypertensive pregnant women . Umbilical artery flow velocity waveforms were recorded using a pulsed Doppler duplex scanner ( ATL Mk V ) and umbilical artery pulsatility index ( PI ) and fetal heart rate ( FHR ) were derived from these recordings . Maternal blood pressure decreased significantly after both drugs . Maternal pulse rate increased after hydralazine but did not change significantly after labetalol . FHR did not change significantly after hydralazine but decreased after labetalol . PI decreased after hydralazine and increased after labetalol‐most fetuses showed little change but a few in each group showed large changes in PI , as did two of five additional patients studied . We attributed the decrease in PI in some fetuses after hydralazine to vasodilation , and the increase in PI in some fetuses after labetalol to vasoconstriction in the fetoplacental circulation , suggesting that fetal beta‐blockade may occur after maternal treatment with labetalol ", "Objective To determine whether nifedipine or prazosin is the more appropriate second‐line antihypertensive agent in pregnancy", "Ninety‐seven women with moderate to severe preeclampsia ( PE ) were allocated at r and om to labetalol or hydralazine treatment . Of these , 22 women with severe PE gave birth to neonates with VLBW ( very low birth weight ≥ 1500 g ) . Seven were allocated to labetalol treatment ( Group A ) , eight to hydralazine treatment ( Group B ) and seven women received both drugs due to poor blood pressure control with a single drug therapy ( Group C ) . No difference in cesarean section rate or in the indication for operative delivery could be seen . Gestational age was 29.9 weeks ( 25.4–32.5 ) in Group A. 28.6 weeks ( 26.6–33.4 ) in Group B and 27.3 weeks ( 26.7–31.1 ) in Group C ( median and range ) . Birth weight did not differ between groups and 13 of the 22 infants weighed below 1000 g. There was a tendency to lower Apgar scores at five minutes in the hydralazine group . Time spent in the neonatal intensive care unit did not differ between groups . Five of the 11 neonates with gestational age (GA)≥28 weeks and three of the seven neonates in GA 29–30 weeks died . Neither the number of infants requiring intermittent positive pressure ventilation or duration of O2‐treatment , nor number of infants with respiratory distress syndrome differed between groups . We did not find any difference in the outcome of the VLBW infants when the hypertensive mother had been treated with either hydralazine or labetalol ", "OBJECTIVE Our aim was to assess the impact of beta-adrenergic blockade during the peripartum period on the previously observed high incidence of ventricular arrhythmias in eclamptic parturients . STUDY DESIGN An open , r and omized comparison of intravenous labetalol versus dihydralazine was conducted in 40 eclamptic subjects in the peripartum period . Cardiac rhythm was assessed by blinded analysis of a 24-hour Holter record by means of the Lown classification of arrhythmias . RESULTS There was a significantly higher incidence of serious ventricular arrhythmias in patients receiving dihydralazine ( 81 % ) than in those receiving labetalol ( 17 % , p labetalol showed a significant decrease in mean heart rate ( p dihydralazine showed a significant increase ( p beta-adrenergic blockade into peripartum hypertensive management of eclampsia significantly reduced the incidence of dangerous ventricular arrhythmias . Myocardial oxygen supply/dem and ratio may be improved by beta-blockade", "OBJECTIVE We sought to compare the efficacies of oral nifedipine and intravenous labetalol in the acute management of hypertensive emergencies of pregnancy . STUDY DESIGN We performed a r and omized double-blind trial of oral nifedipine ( 10 mg ) and intravenous labetalol ( 20 mg ) in 50 peripartum patients with sustained systolic blood pressure of > /=170 mm Hg or diastolic blood pressure of > /=105 mm Hg . Both agents were repeated at sequentially escalating dosages every 20 minutes until a therapeutic goal of systolic blood pressure of time to achievement of the therapeutic goal . Secondary outcome variables were agent failure , urinary output , and adverse effects . Data were analyzed by unpaired t test , Mann-Whitney U test , and analysis of variance for repeated measures . RESULTS The time to achieve the blood pressure goal was significantly shorter with nifedipine ( mean + /- SD , 25 + /- 13.6 minutes ) than with labetalol ( 43.6 + /- 25.4 minutes ; P = .002 ) . No patients required crossover therapy . Urine output was significantly increased ( P nifedipine dosing ( 99 + /- 99 mL ) compared with labetalol ( 44.8 + /- 19.1 mL ) and remained significantly increased at 2 , 6 , 12 , 18 , and 24 hours after initial administration . Adverse effects were infrequent . There were no differences in maternal age , gestational age , number of antepartum patients , or enrollment blood pressures between groups . CONCLUSIONS Both oral nifedipine and intravenous labetalol are effective in the management of acute hypertensive emergencies of pregnancy ; however , nifedipine controls hypertension more rapidly and is associated with a significant increase in urinary output", "OBJECTIVE To compare the efficacy and safety of intravenous dihydralazine with ketanserin in the management of severe hypertension in the third trimester . STUDY DESIGN A double blind r and omised controlled trial , comparing 5 mg dihydralazine with 10 mg ketanserin after an intravenous infusion of 500 ml of a crystalloid solution . Medication was repeated every 20 min till the therapeutic goal of 90 mm Hg was reached , to a maximum of 4 dosages . Main outcome measures were treatment failures and emergency deliveries for fetal distress . RESULTS The therapeutic goal was met more often in patients receiving dihydralazine ( 36/38 compared to 27/42 ; P need for delivery for fetal distress did not differ ( 3 after dihydralazine , 1 after ketanserin , P = 0.29 ) No therapy related perinatal loss occurred , but one mother with an undiagnosed phaechromocytoma died 24 h after receiving dihydralazine . CONCLUSION Ketanserin in this dosage is less effective to lower diastolic blood pressure . The place of a fluid load prior to dihydralazine needs to be further investigated , as fetal heart rate decelerations were less common than previously reported", "Labetalol ( Tr and ate ; Allen & Hanburys ) , a combined alpha- and beta-adrenergic blocking agent , was compared with the more commonly used peripheral vasodilator , dihydrallazine ( Nepresol ; Ciba ) , each administered as an infusion , in the treatment of severe hypertension in 20 primigravidas at greater than or equal to 32 weeks ' gestation . With the dosage regimen used in this study there was a tendency towards more effective blood pressure control with dihydrallazine . The pulse rate was unaffected by labetalol therapy and there were no harmful effects on the neonate or fetus directly attributable to either drug", "OBJECTIVE An open , r and omized , prospect i ve , multicenter trial was conducted to compare the efficacy and safety of intravenous ketanserin , a selective serotonin 2 receptor blocker , with that of intravenous dihydralazine in the management of severe early-onset ( End points of this study were blood pressure control and maternal outcome . STUDY DESIGN Patients with a diastolic blood pressure > 110 mm Hg were r and omly assigned to receive either ketanserin ( n = 22 ) or dihydralazine ( n = 22 ) as initial therapy . Plasma volume expansion preceded antihypertensive treatment , which was administered according to a fixed schedule . RESULTS The reductions in blood pressure with the 2 drugs were similar ; however , adequate blood pressure control was reached significantly earlier with ketanserin ( 84 + / _ 63 vs 171 + /- 142 minutes , P = .017 ) . Occurrence of maternal complications was significantly lower among patients who received ketanserin than among patients who received dihydralazine ( n = 6 vs n = 18 , P = .0007 ) . A significant difference in favor of ketanserin was noted in daily fluid balance . CONCLUSION Antihypertensive efficacies of ketanserin and dihydralazine were comparable , but significantly fewer maternal complications were noted among the patients receiving ketanserin . Ketanserin is an attractive alternative in the management of severe early-onset preeclampsia", "Sixty peripartum patients with diastolic blood pressures ( BP ) 110 mmHg or higher were r and omized in a 2:1 ratio to receive repeated intravenous injections of either labetalol ( 20 - 80 mg ) or hydralazine ( 5 mg ) until the diastolic BP was below 100 mmHg . There were four treatment failures in the labetalol group ( N = 40 ) and none in the hydralazine group ( N = 20 ) . Hydralazine lowered mean arterial pressure ( MAP ) more than did labetalol ( 33.3 + /- 13.2 versus 25.5 + /- 11.2 mmHg ; mean + /- SD ) , but labetalol had a more rapid effect . There was considerable interpatient variability in the dose of labetalol required to control BP , which could not be predicted by any clinical characteristic before therapy . The duration of action also varied in the labetalol group , with the shortest duration occurring in those patients who required the highest dosage for BP control . No significant fetal or neonatal problems ascribable to drug treatment were noted in the 13 instances in which labetalol was given before delivery . However , fetal distress occurred in two of the six cases involving antenatal hydralazine . We conclude that labetalol appears to be a safe and effective alternative to hydralazine for treating hypertension in the peripartum period , but serious rare side effects have not yet been quantified", "OBJECTIVE Data are accumulating to suggest that cerebral perfusion pressure may be either abnormally high or low in preeclampsia and eclampsia . Little is known of the cerebral perfusion pressure effects of magnesium sulfate or nimodipine . Our objective in this study was to compare the change in cerebral perfusion pressure in patients with severe preeclampsia r and omly selected to receive nimodipine or magnesium sulfate . STUDY DESIGN Patients with severe preeclampsia were r and omly selected to receive magnesium sulfate ( 6 g bolus and 2 g/hr intravenous infusion ) or nimodipine ( 60 mg taken orally every 4 hours ) . Transcranial Doppler ultrasonography was used to measure flow velocities in the right and left middle cerebral arteries , and the results were averaged . Measurements were obtained before treatment ( baseline ) and 30 minutes after the magnesium sulfate bolus was completely infused or 30 minutes after the nimodipine was ingested . Studies were performed before any other intervention . The person performing the ultrasonography was unaware of the patient 's group assignment . Estimated cerebral perfusion pressure was calculated with the following formula : Estimated cerebral perfusion pressure = Velocity(mean ) x [ ( Blood pressure(mean ) - Blood pressure(diastolic ) ) /(Velocity(mean ) - Velocity(diastolic ) ) ] . The difference between estimated cerebral perfusion pressure at baseline and after treatment was compared between the 2 groups by means of the Mann-Whitney rank sum test . RESULTS Nine patients were r and omly selected to receive nimodipine and 12 to receive magnesium sulfate . Patient demographics and severity of condition were not significantly different between the 2 groups . The change in estimated cerebral perfusion pressure was significantly different between the groups . Estimated cerebral perfusion pressure increased after nimodipine use and decreased after magnesium sulfate use . CONCLUSION Shortly after administration to patients with severe preeclampsia , nimodipine result ed in increased cerebral perfusion pressure in comparison with magnesium sulfate", "Abstract Objectives . To assess the efficacy and safety of nicardipine in comparison to labetalol in the initial management of severe hypertension in pregnancy . Design . R and omized prospect i ve study . Setting . The obstetric ward of the teaching hospital of Monastir Tunisia . Patients . Sixty consecutive pregnant women admitted beyond the 24th week of pregnancy with severe hypertension . Intervention . Patients were r and omly assigned to receive intravenously for 1 h either labetalol ( n=30 ) or nicardipine ( n=30 ) . Treatment was titrated to achieve a 20 % lowering of blood pressure ( BP ) . Measurements . Maternal BP and heart rate were measured at inclusion and repeatedly during the first hour following the drugs administration . Fetal heart rate was recorded throughout the study period . The main outcome endpoints were the success rate and the length of time needed to achieve the therapeutic goal . The rate of maternal and fetal adverse events and dose adjustments were also analyzed . Results . Labetalol and nicardipine achieved the 20 % lowering in BP in the same proportion ( 63 % and 70 % success rates , respectively ) . Overall nicardipine caused a significantly greater decrease in systolic and diastolic BP . No patient had any episode of hypotension . The length of time to achieve the BP goal was also similar ( 12 vs. 11 min , respectively ) . Both drugs were well tolerated except for a moderate tachycardia observed with the use of nicardipine . Conclusion . Nicardipine and labetalol are effective and safe in the initial treatment of severe hypertension of pregnancy", "Placental blood flow is decreased in pre-eclampsia and is worsened by decreasing blood pressure . Hydralazine , which causes vasodilatation , does not affect placental bed vessels . Calcium channel blockers ( like isradipine ) are vasodilators that do affect placental bed vessels and should improve blood flow even while decreasing blood pressure . The aim of the study was to determine if isradipine ( parenteral and oral ) was better than parenteral hydralazine and oral methyl dopa in severe pre-eclampsia in achieving better control of blood pressure . The study was a prospect i ve r and omised trial performed at The University Hospital of the West Indies . The sample consisted of 39 women with severe pre-eclampsia . Variables examined consisted of blood pressure before and after treatment , the increment in gestational age at delivery related to treatment , fetal Apgar score and birth weight . There were no significant differences in any of these variables between the two groups . Isradipine was as effective as hydralazine in reducing maternal blood pressure and in prolonging pregnancy", "The objective of this study was to evaluate the effectiveness of sublingual isosorbide dinitrate ( ID ) in the acute control of hypertension in patients with severe preeclampsia . A r and omized , double-blind clinical trial with a pre inclusion period of response to hydration and rest was performed in 60 patients with severe preeclampsia . The treatment group ( 30 patients ) received 5 mg of sublingual ID , a dose that could be repeated on a second occasion . The control group consisted of 30 patients who received placebo . Both groups continued with rest and hydration during the study . Maternal blood pressure and fetal heart rate were measured in all patients every 10 min until 1 h was completed . Treatment was considered effective when the diastolic blood pressure could be reduced to between 80 and 100 mm Hg . ID was effective in 56.6 % of the patients in the first 10 min after its administration and in 96.6 % from 40 to 60 min . In the treatment group the systolic and diastolic blood pressures dropped gradually from 171 ± 13 and 113 ± 8 mm Hg , respectively , to 136 ± 14 and 87 ± 9 mm Hg . In the placebo group , blood pressure was not reduced . There was no significant difference in fetal heart rate between both groups throughout the study . In conclusion , ID was shown to be effective in the acute control of hypertension in patients with severe preeclampsia , where high blood pressure persists after a period of rest and hydration", "OBJECTIVES To compare ketanserin with hydralazine in the treatment of hypertension in late pregnancy . STUDY DESIGN R and omised control trial . Ten milligrams ketanserin were compared with 5 mg hydralazine , both given intravenously to 10 patients in each group . Blood pressure , maternal and fetal heart rate and umbilical and arcuate artery Doppler flow velocimetry waveforms were recorded before and every 10 minutes after administration of the drug . RESULTS No significant differences were found between the two drugs in respect of initial blood pressures and readings taken 10 minutes after each 30-minute administration . One patient in the hydralazine group developed severe hypotension and fetal distress for which a caesarean section was performed . No change in the flow velocity waveforms of umbilical and arcuate arteries was noticed . CONCLUSION No unforeseen complications followed the administration of ketanserin . No major differences in the effects of the two drugs could be detected . Ketanserin appears to be safer as no hypotension occurred , and it reduced blood pressure more gradually . As ketanserin could become an alternative to hydralazine , more studies with larger numbers of patients are needed to compare it with hydralazine", "OBJECTIVE To establish the optimal dosage of ketanserin in the treatment of severe hypertension in pregnancy . STUDY DESIGN A double blind prospect i ve r and omised controlled trail , comparing 10 mg ketanserin given as intravenous boluses either every 10 or 20 min , until the therapeutic goal of 90 mmHg ( diastolic blood pressure ) was reached , to a maximum of eight boluses . Main outcome measures were treatment failures and caesarean sections for fetal distress . RESULTS There was no difference in reaching the therapeutic goal between patients receiving 10 mg ketanserin either every 10 or 20 min . CONCLUSION Ketanserin appears to be an attractive medicine in the treatment of severe hypertension in pregnancy , but the optimal dosage could not be established", "OBJECTIVE To determine the efficacy of Nifedipine on postpartum blood Loss in patients with Pregnancy Induced Hypertension ( PIH ) . METHODS 64 cases of PIH were r and omly divided into study group ( n = 32 ) and control group ( n = 32 ) . Before labor Nifedipine 10 mg-20 mg was given three time daily for all cases . In study group Nifedipine was taken orally every 6 hours during the labor course until the end of second stage . In control group Nifedipine was not given in the labor stages . The postpartum blood loss was collected and measured carefully within 2 hours after delivery . RESULTS The amount of pastpartum hemorrhage was ( 359.1 + /- 136.6 ) ml in study group which was significantly higher than that of control group ( 268.5 + /- 110.7 ) ml P postpartum hemorrhage rate in study and control group was 43.75 % and 18.75 % respectively . The difference was statistically significant ( P Nifedipine for PIH cases can increase the amount of postpartum blood loss and rate of postpartum hemorrnage", "Summary : Doppler studies of the uterine and umbilical arteries were performed in 24 acutely hypertensive pregnant women . Women were divided into 2 groups : Group 1 ( diastolic blood pressure (DBP)>110 mm Hg ) received placebo ( n = 6 ) or 10 mg oral nifedipine ( n = 9 ) ; Group 2 ( DBP ≥ 110 mm Hg ) received 10 mg oral nifedipine ( n = 5 ) or 10 mg intravenous hydralazine ( n = 4 ) . Treatment allocations were r and om within groups and the investigator and patient were blind to the treatments . Baseline flow velocity waveforms ( FVW ) and posttreatment FVW 's at 30 , 60 and 120 minutes were recorded . There was no significant difference between baseline and posttreatment FVW indices within or between groups . Placebo was as effective as nifedipine in lowering blood pressure over 2 hours of study . There were no significant adverse effects of treatment", "The prospect i ve feasibility study was design ed to determine whether treatment with antithrombin ( AT ) concentrates could be used for patients with severe preeclampsia to provide clinical efficacy without the full systemic antihypertensive drug . Twenty-nine severe preeclamptic patients ( 24 to 36 weeks of gestation , gestosis index [ GI ] > /= 6 points ) were r and omized to receive AT ( 1500 U/day ) or not . AT was given intravenously once daily for 7 consecutive days . Twenty-four hours of continuous infusion of 5000 U/day of unfractionated heparin was given simultaneously in both groups . There were no statistical differences in the clinical profiles of the two groups . Maternal symptoms were evaluated from the difference of GI before and after treatment , and fetal findings were evaluated from the changes of the biophysical profile score . Improvement was significantly greater in the AT group for both the GI ( P = 0.046 ) and the biophysical profile score ( P = 0.022 ) . The improvement of coagulation parameters was also evaluated . The improvement of plasmin-plasmin inhibitor complex ( PPIC ) , D-dimer levels , and platelet counts was observed in the AT group compared with the non-AT group . The coagulation index as a composite coagulation test parameter showed a significantly improvement in the AT group . No adverse events related to AT were observed . Given that AT plus heparin was significantly better than treatment with heparin alone for improvement of both GI and biophysical profile of infant , it is suggested that therapy with AT alone might be effective enough for severe preeclampsia", "OBJECTIVE The purpose of this study was to determine whether the slower- and longer-acting nifedipine tablets were as effective and safe as the rapid onset and short-acting nifedipine capsules for the treatment of acute severe hypertension in pregnancy . STUDY DESIGN Sixty-four women in the second half of pregnancy who were not in labor r and omly received 10 mg nifedipine tablets ( n = 55 studies ) or 10 mg nifedipine capsules ( n = 74 studies ) if blood pressure was > or = 170/110 mm Hg . Blood pressure , heart rate , and cardiotocography were monitored over the subsequent 90 minutes . Successful treatment was a target blood pressure of 110 to 169/80 to 109 mm Hg after 90 minutes ; unsuccessful treatment included fetal distress at any stage , the requirement for additional treatment ( intravenous hydralazine ) , or the development of hypotension by 90 minutes after treatment . RESULTS Nifedipine capsules lowered blood pressure further ( 28/19 vs 21/13 mm Hg ; P = .03 ) than nifedipine tablets , but more than three quarters of each group had a successful treatment . Twice as many women ( 28 % ) who received nifedipine tablets required a second dose to achieve successful treatment ( P = .05 ) , but fewer women had hypotensive episodes ( P = .001 ) . Fetal distress was uncommon in both groups ( 3%-4 % ) , and both groups were delivered an average of 4 days after the study . CONCLUSION Nifedipine tablets , although of slower onset , are as effective as nifedipine capsules for the rapid treatment of severe hypertension in pregnancy", " Background . Pre‐eclampsia is one of the most serious and common complications of pregnancy . Nifedipine , a calcium channel blocker , and the vasodilator hydralazine have both been used as antihypertensive agents in this condition . The aim of this study was to determine which of these two agents is the most appropriate antihypertensive in the management of severe pre‐eclampsia", "Objective To compare the haemodynamic efficacy of ketanserin ( a selective serotonin2‐receptor blocker ) with dihydralazine in the management of severe early‐onset hypertension in pregnancy", "We conducted a r and omized clinical trial in which patients with severe preeclampsia between 26 - 36 weeks of gestation received either nifedipine ( 10 - 30 mg sublingually , then 40 - 120 mg/day orally ; N=24 ) or hydralazine ( 6.25 - 12.5 mg intravenously , then 80 - 120 mg/day orally ; N=25 ) . Effective control of blood pressure was achieved with nifedipine in 95.8 % of subjects and with hydralazine in 68 % , a statistically significant difference ( P Maternal side effects were minor in both groups . Acute fetal distress developed in one nifedipine subject and in 11 treated with hydralazine . Mean prolongation of gestation was 15.5 ± 10 days with nifedipine and 9.5 ± 11 days with hydralazine , a difference that did not reach statistical significance ( P nifedipine were delivered at more advanced gestational ages ( 34.6 ± 2.3 versus 33.6 ± 2.4 weeks ; statistically not significant ) , weighed more ( 1826 ± 456 versus 1580 ± 499 g ; statistically not significant ) , and tended to have fewer , mainly minor , complications . The average number of days spent in the neonatal intensive care unit was significantly lower in the nifedipine group ( 15.1 versus 32.7 days ; P reduction in total ( maternal and neonatal ) hospitalization related charges for each nifedipine-treated pregnancy . We conclude that nifedipine is an effective , convenient , and low-cost treatment for patients with severe preeclampsia , and is not associated with undesirable side", " Prostagl and in A1 is a potent hypotensive , peripheral vasodilator , a weak oxytocic , antiplatelet aggregator . It improves the renal hemodynamics . Its effect on placental circulation was evaluated ( expressed as systolic/diastolic ratio and umbilical artery resistance index ) in 20 women with severe pre‐eclampsia and 10 normotensive pregnant women , by using the Doppler technique . Moreover , another 10 women with severe pre‐eclampsia received dextrose 5 % as a placebo for comparative purpose s. Significant improvements in both parameters studied were observed in the women with severe pre‐eclampsia . The beneficial changes differed significantly from the recorded values when using dextrose in pre‐eclampsia or prostagl and in A , in normotensive subjects . Such promising data add another important perspective to prostagl and in A , in severe pre‐eclampsia and may open up new avenues for its use in other situations with compromised placental flow", "OBJECTIVE Our purpose was to compare the hemodynamic effects of orally administered nifedipine and intravenously administered labetalol in preeclamptic hypertensive emergencies . STUDY DESIGN Our study was a r and omized , double-blind evaluation of nifedipine and labetalol in women with preeclampsia and a systolic blood pressure > 170 mm Hg or a diastolic blood pressure > 105 mm Hg . Nifedipine or labetalol and placebo were given , so patients received both tablet and intravenous solution . Hemodynamic parameters at dosing and at 15 , 30 , 60 , and 120 minutes were recorded . Outcome measures were cardiac index , systemic vascular resistance index , mean arterial pressure , and heart rate . Data were analyzed by repeated- measures analysis of variance ( Friedman test ) with Dunn posttests , the Mann-Whitney U test , and the chi(2 ) test with the Yates correction . Significance was set at P the nifedipine group ( n = 6 ) had a cardiac index of 3.08 + /- 0.51 L/min per square meter . There was a 43 % increase in the cardiac index after nifedipine administration ( P = .0008 ) . There was no significant effect in the labetalol group ( P = .697 ) . There was a significant decrease in the systemic vascular resistance index after nifedipine dosing ( P = .002 ) but no significant effect on this index after labetalol use ( P = .479 ) . The mean arterial pressure was significantly affected in both groups as follows : nifedipine , P = . 001 ; labetalol , P = .004 . The post analysis showed significance at 60 minutes for both . An insignificant increase in heart rate with nifedipine ( P = .147 ) and a significant decrease with labetalol ( P = . 034 ) were noted . CONCLUSIONS Nifedipine increases cardiac index , whereas labetalol may not do so", "Patients with acute pregnancy-related hypertension were r and omized to treatment with 200 mg oral labetalol or 10 mg intramuscular hydralazine . Labetalol was found to be at least as effective , more predictable , more acceptable and produced no change in heart rate compared to hydralazine" ]	41188d58-06ff-11f0-808a-c43d1ab1c353
Background Autism spectrum disorder ( ASD ) is characterised by significant impairment in social communication and the presence of restrictive and repetitive behaviour or interest . Intervention during early childhood could decrease ASD symptoms . We aim ed to identify the most effective intervention based on cognitive , developmental , and behavioural approaches and the factors that impact the effectiveness of the intervention . Methods We performed a systematic review and meta- analysis of existing interventions for ASD in preschool-aged children . Electronic data bases were search ed for related articles with r and omised controlled trial ( RCT ) design s published between 2001 to 2015 . Outcome measures were communication , behavioural and cognitive skills , reported as st and ardised mean differences ( SMD ) compared to a control group . A R and om-effects model was utilised to calculate the pooled estimate effect . Between- study variability was also assessed . The registering number of this study is CRD42017035354 . Findings Out of the initial 5174 studies that were identified , there were 14 RCTs ( 746 children ) that were included in the final systematic review and meta- analysis . Pooled estimate effect provided by r and om-effects model was 0.23 ( 95 % confidence interval , CI [ 0.08 - 0.37 ] ) with no between- study heterogeneity ( I2 = 0.00 % , p = 0.0018 ) . Three studies of music therapy interventions provided the greatest outcome effects with a shorter duration and lower intensity . SMD for music therapies ranged from 0.40 to 0.62 with 95 % CI [ 0.22 to 1.85 ] . The quality of the health care provider , the duration , and the intensity of intervention played an important role in the effectiveness of the intervention . Interpretation Music therapy appears to be an effective tool for improving social interaction in preschool-aged children with ASD . However , more evidence -based trials are required to further vali date the effectiveness of music therapy in ASD	[ "This study reports results of a r and omized controlled trial aim ed at joint attention ( JA ) and symbolic play ( SP ) in preschool children with autism , with prediction to language outcome 12 months later . Participants were 58 children ( 46 boys ) with autism between 3 and 4 years of age . Children were r and omized to a JA intervention , an SP intervention , or control group . Interventions were conducted 30 min daily for 5 - 6 weeks . Assessment s of JA skills , SP skills , mother-child interactions , and language development were collected at 4 time points : pre- and postintervention and 6 and 12 months postintervention by independent testers . Results indicate that expressive language gains were greater for both treatment groups compared with the control group , and results could not be explained by differences in other interventions in which children participated . For children beginning treatment with the lowest language levels , the JA intervention improved language outcome significantly more than did the SP or control interventions . These findings suggest clinical ly significant benefits of actively treating JA and SP skills in young children with autism", "The current study is a r and omized clinical trial evaluating the efficacy of Focused Playtime Intervention ( FPI ) in a sample of 70 children with Autism Spectrum Disorder . This parent-mediated intervention has previously been shown to significantly increase responsive parental communication ( Siller et al. in J Autism Dev Disord 43:540–555 , 2013a ) . The current analyses focus on children ’s attachment related outcomes . Results revealed that children who were r and omly assigned to FPI showed bigger increases in attachment-related behaviors , compared to children assigned to the control condition . Significant treatment effects of FPI were found for both an observational measure of attachment-related behaviors elicited during a brief separation-reunion episode and a question naire measure evaluating parental perceptions of child attachment . The theoretical and clinical implication s of these findings are discussed", "OBJECTIVE : To conduct a r and omized , controlled trial to evaluate the efficacy of the Early Start Denver Model ( ESDM ) , a comprehensive developmental behavioral intervention , for improving outcomes of toddlers diagnosed with autism spectrum disorder ( ASD ) . METHODS : Forty-eight children diagnosed with ASD between 18 and 30 months of age were r and omly assigned to 1 of 2 groups : ( 1 ) ESDM intervention , which is based on developmental and applied behavioral analytic principles and delivered by trained therapists and parents for 2 years ; or ( 2 ) referral to community providers for intervention commonly available in the community . RESULTS : Compared with children who received community-intervention , children who received ESDM showed significant improvements in IQ , adaptive behavior , and autism diagnosis . Two years after entering intervention , the ESDM group on average improved 17.6 st and ard score points ( 1 SD : 15 points ) compared with 7.0 points in the comparison group relative to baseline scores . The ESDM group maintained its rate of growth in adaptive behavior compared with a normative sample of typically developing children . In contrast , over the 2-year span , the comparison group showed greater delays in adaptive behavior . Children who received ESDM also were more likely to experience a change in diagnosis from autism to pervasive developmental disorder , not otherwise specified , than the comparison group . CONCLUSIONS : This is the first r and omized , controlled trial to demonstrate the efficacy of a comprehensive developmental behavioral intervention for toddlers with ASD for improving cognitive and adaptive behavior and reducing severity of ASD diagnosis . Results of this study underscore the importance of early detection of and intervention in autism", "Summary Background Results of small trials suggest that early interventions for social communication are effective for the treatment of autism in children . We therefore investigated the efficacy of such an intervention in a larger trial . Methods Children with core autism ( aged 2 years to 4 years and 11 months ) were r and omly assigned in a one-to-one ratio to a parent-mediated communication-focused ( Preschool Autism Communication Trial [ PACT ] ) intervention or treatment as usual at three specialist centres in the UK . Those assigned to PACT were also given treatment as usual . R and omisation was by use of minimisation of probability in the marginal distribution of treatment centre , age ( ≤42 months or > 42 months ) , and autism severity ( Autism Diagnostic Observation Schedule-Generic [ ADOS-G ] algorithm score 12–17 or 18–24 ) . Primary outcome was severity of autism symptoms ( a total score of social communication algorithm items from ADOS-G , higher score indicating greater severity ) at 13 months . Complementary secondary outcomes were measures of parent-child interaction , child language , and adaptive functioning in school . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N58133827 . Results 152 children were recruited . 77 were assigned to PACT ( London [ n=26 ] , Manchester [ n=26 ] , and Newcastle [ n=25 ] ) ; and 75 to treatment as usual ( London [ n=26 ] , Manchester [ n=26 ] , and Newcastle [ n=23 ] ) . At the 13-month endpoint , the severity of symptoms was reduced by 3·9 points ( SD 4·7 ) on the ADOS-G algorithm in the group assigned to PACT , and 2·9 ( 3·9 ) in the group assigned to treatment as usual , representing a between-group effect size of −0·24 ( 95 % CI −0·59 to 0·11 ) , after adjustment for centre , sex , socioeconomic status , age , and verbal and non-verbal abilities . Treatment effect was positive for parental synchronous response to child ( 1·22 , 0·85 to 1·59 ) , child initiations with parent ( 0·41 , 0·08 to 0·74 ) , and for parent-child shared attention ( 0·33 , −0·02 to 0·68 ) . Effects on directly assessed language and adaptive functioning in school were small . Interpretation On the basis of our findings , we can not recommend the addition of the PACT intervention to treatment as usual for the reduction of autism symptoms ; however , a clear benefit was noted for parent-child dyadic social communication . Funding UK Medical Research Council , and UK Department for Children , Schools and Families", "BACKGROUND With rates of autism diagnosis continuing to rise , there is an urgent need for effective and efficient service delivery models . Pivotal Response Treatment ( PRT ) is considered an established treatment for autism spectrum disorder ( ASD ) ; however , there have been few well-controlled studies with adequate sample size . The aim of this study was to conduct a r and omized controlled trial to evaluate PRT parent training group ( PRTG ) for targeting language deficits in young children with ASD . METHODS Fifty-three children with autism and significant language delay between 2 and 6 years old were r and omized to PRTG ( N = 27 ) or psychoeducation group ( PEG ; N = 26 ) for 12 weeks . The PRTG taught parents behavioral techniques to facilitate language development . The PEG taught general information about ASD ( clinical trial NCT01881750 ; http://www . clinical trials.gov ) . RESULTS Analysis of child utterances during the structured laboratory observation ( primary outcome ) indicated that , compared with children in the PEG , children in the PRTG demonstrated greater improvement in frequency of utterances ( F(2 , 43 ) = 3.53 , p = .038 , d = 0.42 ) . Results indicated that parents were able to learn PRT in a group format , as the majority of parents in the PRTG ( 84 % ) met fidelity of implementation criteria after 12 weeks . Children also demonstrated greater improvement in adaptive communication skills ( Vinel and -II ) following PRTG and baseline Mullen visual reception scores predicted treatment response to PRTG . CONCLUSIONS This is the first r and omized controlled trial of group-delivered PRT and one of the largest experimental investigations of the PRT model to date . The findings suggest that specific instruction in PRT results in greater skill acquisition for both parents and children , especially in functional and adaptive communication skills . Further research in PRT is warranted to replicate the observed results and address other core ASD symptoms", "Imitation is an early skill thought to play a role in social development , leading some to suggest that teaching imitation to children with autism should lead to improvements in social functioning . This study used a r and omized controlled trial to evaluate the effect of a focused imitation intervention on initiation of joint attention and social-emotional functioning in 27 young children with autism . Results indicated the treatment group made significantly more gains in joint attention initiations at post-treatment and follow-up and social-emotional functioning at follow-up than the control group . Although gains in social functioning were associated with treatment , a mediation analysis did not support imitation as the mechanism of action . These findings suggest the intervention improves social functioning in children with ASD", "The purpose of this study was to investigate the effects of improvisational music therapy on joint attention behaviors in pre-school children with autism . It was a r and omized controlled study employing a single subject comparison design in two different conditions , improvisational music therapy and play sessions with toys , and using st and ardized tools and DVD analysis of sessions to evaluate behavioral changes in children with autism . The overall results indicated that improvisational music therapy was more effective at facilitating joint attention behaviors and non-verbal social communication skills in children than play . Session analysis showed significantly more and lengthier events of eye contact and turn-taking in improvisational music therapy than play sessions . The implication s of these findings are discussed further", "CONTEXT To our knowledge , there is no published information on the epidemiology of autism spectrum disorders ( ASDs ) in adults . If the prevalence of autism is increasing , rates in older adults would be expected to be lower than rates among younger adults . OBJECTIVE To estimate the prevalence and characteristics of adults with ASD living in the community in Engl and . DESIGN A stratified , multiphase r and om sample was used in the third national survey of psychiatric morbidity in adults in Engl and in 2007 . Survey data were weighted to take account of study design and nonresponse so that the results were representative of the household population . SETTING General community ( ie , private households ) in Engl and . PARTICIPANTS Adults ( people 16 years or older ) . MAIN OUTCOME MEASURES Autism Diagnostic Observation Schedule , Module 4 in phase 2 vali date d against the Autism Diagnostic Interview-Revised and Diagnostic Interview for Social and Communication Disorders in phase 3 . A 20-item subset of the Autism-Spectrum Quotient self-completion question naire was used in phase 1 to select respondents for phase 2 . Respondents also provided information on sociodemographics and their use of mental health services . RESULTS Of 7461 adult participants who provided a complete phase 1 interview , 618 completed phase 2 diagnostic assessment s. The weighted prevalence of ASD in adults was estimated to be 9.8 per 1000 ( 95 % confidence interval , 3.0 - 16.5 ) . Prevalence was not related to the respondent 's age . Rates were higher in men , those without educational qualifications , and those living in rented social ( government-financed ) housing . There was no evidence of increased use of services for mental health problems . CONCLUSIONS Conducting epidemiologic research on ASD in adults is feasible . The prevalence of ASD in this population is similar to that found in children . The lack of an association with age is consistent with there having been no increase in prevalence and with its causes being temporally constant . Adults with ASD living in the community are socially disadvantaged and tend to be unrecognized", "Tests of mediation in treatment trials can illuminate processes of change and suggest causal influences in development . We conducted a mediation analysis of a previously published r and omised controlled trial of parent-mediated communication-focused treatment for autism against ordinary care , with 28 children aged 2–5 years ( Aldred et al. in J Child Psychol Psychiatr 45:1–11 , 2004 ) . The hypothesised mediating process , targeted by the intervention , was an increase in parental synchronous response within parent – child interaction . The results showed partial mediation , with change in synchrony accounting for 34 % of the positive intervention effect on autism symptomatology ( Autism Diagnostic Observation Schedule communication and social domain algorithm ) ; the result was confirmed by bootstrap estimation . Improved parental synchronous response to child communication can alter short-term autism symptom outcome with targeted therapy", "Aim : To determine the effect of parent education on adaptive behaviour , autism symptoms and cognitive/ language skills of young children with autistic disorder . Method : A r and omised group comparison design involving a parent education and counselling intervention and a parent education and behaviour management intervention to control for parent skills training and a control sample . Two rural and two metropolitan regions were r and omly allocated to intervention groups ( n = 70 ) or control ( n = 35 ) . Parents from autism assessment services in the intervention regions were r and omly allocated to parent education and behaviour management ( n = 35 ) or parent education and counselling ( n = 35 ) . Results : Parent education and behaviour management result ed in significant improvement in adaptive behaviour and autism symptoms at 6 months follow-up for children with greater delays in adaptive behaviour . Parent education and behaviour management was superior to parent education and counselling . We conclude that a 20-week parent education programme including skills training for parents of young children with autistic disorder provides significant improvements in child adaptive behaviour and symptoms of autism for low-functioning children", "This study compared a common form of Applied Behavior Analysis Verbal Behavior ( ABA VB ) approach and music incorporated with ABA VB method as part of developmental speech- language training in the speech production of children with Autism Spectrum Disorders ( ASD ) . This study explored how the perception of musical patterns incorporated in ABA VB operants impacted the production of speech in children with ASD . Participants were 22 children with ASD , age range 3 to 5 years , who were verbal or pre verbal with presence of immediate echolalia . They were r and omly assigned a set of target words for each of the 3 training conditions : ( a ) music incorporated ABA VB , ( b ) speech ( ABA VB ) and ( c ) no-training . Results showed both music and speech trainings were effective for production of the four ABA verbal operants ; however , the difference between music and speech training was not statistically different . Results also indicated that music incorporated ABA VB training was most effective in echoic production , and speech training was most effective in tact production . Music can be incorporated into the ABA VB training method , and musical stimuli can be used as successfully as ABA VB speech training to enhance the functional verbal production in children with ASD", "The study evaluates a social-communication-based approach to autism intervention aim ed at improving the social interaction skills of children with autism spectrum disorder . We report preliminary results from an ongoing r and omized controlled trial of 51 children aged 2 years 0 months to 4 years 11 months . Participants were assigned to either a target treatment or community treatment group . Families in the target treatment group were given 2 hours of therapy and coaching each week in an intervention emphasizing social-interaction and the parent-child relationship . Children in the community treatment group received a variety of services averaging 3.9 hours per week . After 12 months , outcomes were measured to determine changes in the groups in social interaction and communication . In addition , a regression analysis was conducted to determine whether changes in social interaction skills were associated with language development . Results suggest that children in the treatment group made significantly greater gains in social interaction skills in comparison to the community treatment group , but no between-group differences were found for st and ard language assessment s. Initiation of joint attention , involvement , and severity of language delay were found to be significantly associated with improvement of language skills in children with autism . Finally caregiver skills targeted by the intervention were found to be significantly associated with changes in children ’s interaction skills", "BACKGROUND Deficits in joint attention ( JA ) and joint engagement ( JE ) represent a core problem in young children with autism as these affect language and social development . Studies of parent-mediated and specialist-mediated JA-intervention suggest that such intervention may be effective . However , there is little knowledge about the success of the intervention when done in preschools . AIM Assess the effects of a preschool-based JA-intervention . METHODS 61 children ( 48 males ) with autistic disorder ( 29 - 60 months ) were r and omized to either 8 weeks of JA-intervention , in addition to their preschool programs ( n = 34 ) , or to preschool programs only ( n = 27 ) . The intervention was done by preschool teachers with weekly supervision by trained counselors from Child and Adolescent Mental Health Clinics ( CAMHC ) . Changes in JA and JE were measured by blinded independent testers using Early Social Communication Scale ( ESCS ) and video taped preschool teacher-child and mother-child play at baseline and post-intervention . CLINICAL TRIALS REGISTRATION Clinical trials.gov : NCT00378157 . RESULTS Intention-to-treat analysis showed significant difference between the intervention and the control group , with the intervention group yielding more JA initiation during interaction with the preschool teachers . The effect generalized to significantly longer duration of JE with the mothers . CONCLUSIONS This is the first r and omized study to show positive and generalized effects of preschool-based JA-intervention", "Objective : This study aim ed to ( 1 ) investigate whether provision of a home-based program in addition to a center-based program improves development in young children with disabilities and coping abilities of their families and ( 2 ) describe the characteristics of children and families who benefit most from the intervention . Methods : Fifty-nine children , aged 3–5 years , with no cerebral palsy , participated in the study . Half of the group was r and omized to receive an additional program in their homes . A special education teacher provided 40 visits over 12 months working with the families to help generalize skills to the home environment and assist with their concerns . All children were assessed before and after the intervention , and families completed question naires assessing family stress , support , and empowerment on both occasions . Differences in change over time and between the intervention and control group were analyzed by repeated measures and the association between characteristics of children and families with improved outcome by multivariate analysis of variance . Results : Change in cognitive development and behavior ( in the centers ) over time favored the children who received the extra intervention ( p = .007 and p = .007 , respectively ) . The groups did not differ on any of the family measures of change . Multivariate analysis of variance revealed more improvement for children in the intervention group from higher than lower stressed families . Conclusions : Results suggest the need for daily reinforcement of skills learned at the center-based program and the importance of involving families , especially those with few re sources and relatively high stress" ]	41188d94-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Infantile colic is typically defined as full-force crying for at least three hours per day , on at least three days per week , for at least three weeks . Infantile colic affects a large number of infants and their families worldwide . Its symptoms are broad and general , and while not indicative of disease , may represent a serious underlying condition in a small percentage of infants who may need a medical assessment . Probiotics are live microorganisms that alter the microflora of the host and provide beneficial health effects . The most common probiotics used are of Lactobacillus , Bifidobacterium and Streptococcus . There is growing evidence to suggest that intestinal flora in colicky infants differ from those in healthy infants , and it is suggested that probiotics can redress this balance and provide a healthier intestinal microbiota l and scape . The low cost and easy availability of probiotics makes them a potential prophylactic solution to reduce the incidence and prevalence of infantile colic . OBJECTIVES To evaluate the efficacy and safety of prophylactic probiotics in preventing or reducing severity of infantile colic . SEARCH METHODS In January 2018 we search ed CENTRAL , MEDLINE , Embase , PsycINFO , CINAHL , 10 other data bases and two trials registers . In addition , we h and search ed the abstract s of relevant meetings , search ed reference lists , ran citation search es of included studies , and contacted authors and experts in the field , including the manufacturers of probiotics , to identify unpublished trials . SELECTION CRITERIA R and omised control trials ( RCTs ) of newborn infants less than one month of age without the diagnosis of infantile colic at recruitment . We included any probiotic , alone or in combination with a prebiotic ( also known as synbiotics ) , versus no intervention , another intervention(s ) or placebo , where the focus of the study was the effect of the intervention on infantile colic . DATA COLLECTION AND ANALYSIS We used st and ard method ological procedures of Cochrane . MAIN RESULTS Our search yielded 3284 records , and of these , we selected 21 reports for full-text review . Six studies with 1886 participants met our inclusion criteria , comparing probiotics with placebo . Two studies examined Lactobacillus reuteri DSM , two examined multi-strain probiotics , one examined Lactobacillus rhamnosus , and one examined Lactobacillus paracasei and Bifidobacterium animalis . Two studies began probiotics during pregnancy and continued administering them to the baby after birth . We considered the risk of bias for r and omisation as low for all six trials ; for allocation concealment as low in two studies and unclear in four others . All studies were blinded , and at low risk of attrition and reporting bias . A r and om-effects meta- analysis of three studies ( 1148 participants ) found no difference between the groups in relation to occurrence of new cases of colic : risk ratio ( RR ) 0.46 , 95 % confidence interval ( CI ) 0.18 to 1.19 ; low-certainty evidence ; I2 = 72%.A r and om-effects meta- analysis of all six studies ( 1851 participants ) found no difference between the groups in relation to serious adverse effects ( RR 1.02 , 95 % CI 0.14 to 7.21 ; low-certainty evidence ; I2 not calculable ( only four serious events for one comparison , two in each group : meconium plug obstruction , patent ductus arteriosus and neonatal hepatitis).A r and om-effects meta- analysis of three studies ( 707 participants ) found a mean difference ( MD ) of -32.57 minutes per day ( 95 % CI -55.60 to -9.54 ; low-certainty evidence ; I2 = 93 % ) in crying time at study end in favour of probiotics . A subgroup analysis of the most studied agent , Lactobacillus reuteri , showed a reduction of 44.26 minutes in daily crying with a r and om-effects model ( 95 % CI -66.6 to -21.9 ; I2 = 92 % ) , in favour of probiotics . AUTHORS ' CONCLUSIONS There is no clear evidence that probiotics are more effective than placebo at preventing infantile colic ; however , daily crying time appeared to reduce with probiotic use compared to placebo . There were no clear differences in adverse effects . We are limited in our ability to draw conclusions by the certainty of the evidence , which we assessed as being low across all three outcomes , meaning that we are not confident that these results would not change with the addition of further research	[ "Background . There is controversy regarding whether hypersensitivity to food proteins contributes to colic among breastfed infants . Methods . A r and omized , controlled trial of a low-allergen maternal diet was conducted among exclusively breastfed infants presenting with colic . In the active arm , mothers excluded cow 's milk , eggs , peanuts , tree nuts , wheat , soy , and fish from their diet ; mothers in the control group continued to consume these foods . Outcomes were assessed after 7 days , as the change in cry/fuss duration over 48 hours , with vali date d charts . The primary end point was a reduction in cry/fuss duration of ≥25 % from baseline . Mothers also assessed the responses to diet with categorical and visual analog scales . Results . Of 107 infants , 90 completed the trial ( mean age : 5.7 weeks ; range : 2.9–8.6 weeks ; 54 male infants ) . Infants in both groups presented with significant distress ( geometric mean : low-allergen group : 690 minutes per 48 hours ; control group : 631 minutes per 48 hours ) . In follow-up assessment s on days 8 and 9 , there were significantly more responders in the low-allergen group ( 74 % vs 37 % ) , ie , an absolute risk reduction of 37 % ( 95 % confidence interval : 18–56 % ) . Cry/fuss duration per 48 hours was reduced by a substantially greater amount in the low-allergen group ; the adjusted geometric mean ratio was 0.79 ( 95 % confidence interval : 0.63–0.97 ) , ie , an average reduction of 21 % ( 95 % confidence interval : 3–37 % ) . Mothers ' subjective assessment s of the responses to diet indicated little difference between the groups . Conclusion . Exclusion of allergenic foods from the maternal diet was associated with a reduction in distressed behavior among breastfed infants with colic presenting in the first 6 weeks of life", "Background Probiotics have rarely been studied in young healthy infants from low-income countries . This phase I study investigated the safety and acceptability of two probiotics in Bangladesh . Methods Healthy infants aged four to twelve weeks from urban slums in Bangladesh were r and omized to one of three different intervention dosing arms ( daily , weekly , biweekly – once every two weeks ) of Lactobacillus reuteri DSM 17938 and Bifidobacterium longum subspecies infantis 35624 over one month or to a fourth arm that received no probiotics . All subjects were followed for two additional months . Reported gastrointestinal and respiratory symptoms as well as breastfeeding rates , hospitalizations , differential withdrawals , and caretakers ’ perception of probiotic use were compared among arms . Results In total , 160 infants were r and omized ( 40 to each arm ) with 137 ( Daily n = 35 , Weekly n = 35 , Biweekly n = 35 , Control n = 32 ) followed up for a median of twelve weeks ; 113 completed the study . Illness and breastfeeding rates were similar across all arms . Ten hospitalizations unrelated to probiotic use occurred . Forty eight percent of the caretakers of infants in intervention arms believed that probiotics improved their baby ’s health . Conclusions These two commonly used probiotics appeared safe and well-accepted by Bangladeshi families . Trial registration Clinical Trials.gov NCT01899378 . Registered July 10 , 2013", "OBJECTIVE To determine whether administration of Lactobacillus reuteri ( L reuteri ) DSM 17938 is beneficial in breastfed infants with infantile colic . STUDY DESIGN Eighty infants aged 50 % ) breastfed were r and omly assigned to receive L reuteri DSM 17938 ( 10(8 ) colony-forming units ) ( n = 40 ) or an identically appearing and tasting placebo ( n = 40 ) , both orally , in 5 drops , 1 time daily , for 21 days . The primary outcome measures were the treatment success , defined as the percentage of children achieving a reduction in the daily average crying time ≥ 50 % , and the duration of crying ( minutes per day ) at 7 , 14 , 21 , and 28 days after r and omization . RESULTS The rate of responders to treatment was significantly higher in the probiotic group compared with the placebo group at day 7 ( P = .026 ) , at day 14 ( relative risk ( RR ) 4.3 , 95 % CI 2.3 - 8.7 ) , at day 21 ( RR 2.7 , 95 % CI 1.85 - 4.1 ) , and at day 28 ( RR 2.5 , 95 % CI 1.8 - 3.75 ) . In addition , throughout the study period , the median crying time was significantly reduced in the probiotic group compared with the control group . CONCLUSION Exclusively or predominantly breastfed infants with infantile colic benefit from the administration of L reuteri DSM 17938 compared with placebo", "Background : Probiotic supplementation to women during pregnancy and lactation can modulate breast milk composition , with immune benefits being transferred to their infants . Aim : The aim of the study was to evaluate the effect of high-dose probiotic supplementation to women during late pregnancy and lactation on cytokine profile and secretory IgA ( sIgA ) in breast milk and thus to study if differences in breast milk composition can affect lactoferrin and sIgA levels in stool sample s of newborns . The safety of maternal probiotic administration on neonatal growth pattern and gastrointestinal symptoms were also evaluated . Methods : In a double-blind , placebo-controlled , r and omized trial , 66 women took either the probiotic ( n = 33 ) or a placebo ( n = 33 ) daily . Levels of interleukins ( IL-6 , IL-10 and IL-1β ) , transforming growth factor-β1 ( TGF-β1 ) , and sIgA in breast milk ; and the level of sIgA and lactoferrin in newborn stool sample s were analyzed at birth and then again at one month of life . Antropometrical evaluation and analysis of gastrointestinal events in newborns was also performed . Results : Probiotic maternal consumption had a significant impact on IL6 mean values in colostrum and on IL10 and TGF-β1 mean values in mature breast milk . Fecal sIgA mean values were higher in newborns whose mothers took the probiotic product than in the control group . Probiotic maternal supplementation seems to decrease incidence of infantile colic and regurgitation in infants . Conclusion : High-dose multi-strain probiotic administration to women during pregnancy influences breast milk cytokines pattern and sIgA production in newborns , and seems to improve gastrointestinal functional symptoms in infants", "Background Infant colic , characterised by excessive crying/fussing for no apparent cause , affects up to 20 % of infants under three months of age and is a great burden to families , health professionals and the health system . One promising approach to improving its management is the use of oral probiotics . The Baby Biotics trial aims to determine whether the probiotic Lactobacillus reuteri DSM 17938 is effective in reducing crying in infants less than three months old ( when compared to placebo . Methods / Design Design : Double-blind , placebo-controlled r and omised trial in Melbourne , Australia . Participants : 160 breast and formula fed infants less than three months old who present either to clinical or community services and meet Wessel ’s criteria of crying and /or fussing . Intervention : Oral once-daily Lactobacillus reuteri ( 1x108 cfu ) versus placebo for one month . Primary outcome : Infant crying/fussing time per 24 hours at one month . Secondary outcomes : i ) number of episodes of infant crying/fussing per 24 hours and ii ) infant sleep duration per 24 hours ( at 7 , 14 , 21 , 28 days and 6 months ) ; iii ) maternal mental health scores , iv ) family functioning scores , v ) parent quality adjusted life years scores , and vi ) intervention cost-effectiveness ( at one and six months ) ; and vii ) infant faecal microbiota diversity , viii ) infant faecal calprotectin levels and ix ) Eschericia coli load ( at one month only ) . Analysis : Primary and secondary outcomes for the intervention versus control groups will be compared with t tests and non-parametric tests for continuous data and chi squared tests for dichotomous data . Regression models will be used to adjust for potential confounding factors . Intention-to-treat analysis will be applied . Discussion An effective , practical and acceptable intervention for infant colic would represent a major clinical advance . Because our trial includes breast and formula-fed babies , our results should generalise to most babies with colic . If cost-effective , the intervention ’s simplicity is such that it could be widely taken up as a new st and ard of care in the primary and secondary care sectors . Trial Registration Current Controlled Trials IS RCT", "The addition of probiotics to infant formula has been shown to be an efficient way to increase the number of beneficial bacteria in the intestine in order to promote a gut flora resembling that of breast-fed infants . The objective of the present study was to evaluate the safety and tolerance of a combination of two probiotic strains in early infancy . A group of 126 newborns were r and omised to receive a prebiotic-containing starter formula supplemented with Lactobacillus paracasei ssp . paracasei and Bifidobacterium animalis ssp . lactis or the same formula without probiotics for the first 3 months of life . A total of eighty infants continued the study until they were aged 6 months . Growth measurements were taken monthly at healthy baby clinics . Diaries were used to monitor behaviour , infections , use of antibiotics , as well as stool characteristics . Normal growth occurred in all infants and no statistically significant differences were detected between the probiotics group and the control group for gain in weight , length and head circumference . Infants in the probiotics group produced softer and more frequent stools during the first 3 months of life . No differences were found in crying and sleeping hours , number of parent-diagnosed infections , antibiotic use , visits to the general practitioner and number of adverse events . The use of a prebiotic-containing starter formula supplemented with L. paracasei ssp . paracasei and B. animalis ssp . lactis in early infancy is safe , well tolerated and has no adverse effects on growth and infant behaviour", "OBJECTIVE . The goal was to test the hypothesis that oral administration of Lactobacillus reuteri in a prospect i ve r and omized study would improve symptoms of infantile colic . METHODS . Ninety breastfed colicky infants were assigned r and omly to receive either the probiotic L reuteri ( 108 live bacteria per day ) or simethicone ( 60 mg/day ) each day for 28 days . The mothers avoided cow 's milk in their diet . Parents monitored daily crying times and adverse effects by using a question naire . RESULTS . Eighty-three infants completed the trial : 41 in the probiotic group and 42 in the simethicone group . The infants were similar regarding gestational age , birth weight , gender , and crying time at baseline . Daily median crying times in the probiotic and simethicone groups were 159 minutes/day and 177 minutes/day , respectively , on the seventh day and 51 minutes/day and 145 minutes/day on the 28th day . On day 28 , 39 patients ( 95 % ) were responders in the probiotic group and 3 patients ( 7 % ) were responders in the simethicone group . No adverse effects were reported . CONCLUSIONS . In our cohort , L reuteri improved colicky symptoms in breastfed infants within 1 week of treatment , compared with simethicone , which suggests that probiotics may have a role in the treatment of infantile colic", "CONTEXT The section of a research article most likely to be read is the abstract , and therefore it is particularly important that the abstract reflect the article faithfully . OBJECTIVE To assess abstract s accompanying research articles published in 6 medical journals with respect to whether data in the abstract could be verified in the article itself . DESIGN Analysis of simple r and om sample s of 44 articles and their accompanying abstract s published during 1 year(July 1 , 1996-June 30 , 1997 ) in each of 5 major general medical journals ( Annals of Internal Medicine , BMJ , JAMA , Lancet , and New Engl and Journal of Medicine ) and a consecutive sample of 44 articles published during 15 months ( July 1 , 1996-August 15 , 1997 ) in the CMAJ . MAIN OUTCOME MEASURE Abstract s were considered deficient if they contained data that were either inconsistent with corresponding data in the article 's body ( including tables and figures ) or not found in the body at all . RESULTS The proportion of deficient abstract s varied widely ( 18%-68 % ) and to a statistically significant degree ( P<.001 ) among the 6 journals studied . CONCLUSIONS Data in the abstract that are inconsistent with or absent from the article 's body are common , even in large-circulation general medical journals", "Objective : The aim of this study was to evaluate the suspicion of cow's-milk allergy in infants with unspecific gastrointestinal ( GI ) symptoms using the double-blind , placebo-controlled food challenge . Methods : A prospect i ve cohort study , which recruited 57 consecutive children with gastrointestinally manifested symptoms suspected of cow's-milk allergy . All patients underwent a 5-day double-blind , placebo-controlled food challenge for cow 's milk . Results : The median age of the patients was 8.7 months . None had measurable cow's-milk – specific IgE. The food challenge was positive in 18 ( 32 % ) cases , with symptoms manifesting within 48 hours in 17 of 18 cases . The only symptom that correlated with the positive challenge was loose stools , reported as a presenting symptom in 78 % of challenge-positive and in 46 % of challenge-negative children ( P = 0.043 ) . During active challenge , the respective proportions were 82 % and 2 % ( P No serious adverse effects were manifested during the challenges . In the challenge-negative group , significant placebo reactions occurred in 18 ( 46 % ) patients . In the challenge-negative children , adult-type hypolactasia genotype CC frequency was higher ( 31 % , P = 0.033 ) than national prevalence of 18 % . Conclusions : In an infant with unspecific GI symptoms suspected of cow's-milk allergy , this diagnosis is seldom confirmed . Other reasons for the troublesome GI symptoms should also be identified", "OBJECTIVES To determine the benefits of Lactobacillus rhamnosus GG ( LGG ) in an extensively hydrolyzed casein formula ( EHCF ) in improving hematochezia and fecal calprotectin over EHCF alone . STUDY DESIGN Fecal calprotectin was compared in 30 infants with hematochezia and 4 weeks after milk elimination with that of a healthy group . We also compared fecal calprotectin and hematochezia on 26 formula-fed infants r and omly assigned to EHCF with LGG ( Nutramigen LGG ) ( EHCF + LGG ) or without ( Nutramigen ) ( EHCF - LGG ) and on 4 breastfed infants whose mothers eliminated dairy . RESULTS Fecal calprotectin in those with hematochezia was significantly higher than in comparisons ( mean + /- SD 325.89 + /- 152.31 vs 131.97 + /- 37.98 microg/g stool , t = 6.79 , P fecal calprotectin decreased to 50 % of baseline but was still significantly higher than in comparisons ( 157.5 + /- 149.13 vs 93.72 + /- 36.65 microg/g , P = .03 ) . Fecal calprotectin mean decrease was significantly larger among EHCF + LGG compared with EHCF - LGG ( -214.5 + /- 107.93 vs -112.7 + /- 105.27 microg/g , t = 2.43 , P = .02 ) . At 4 weeks , none of the EHCF + LGG had blood in stools , and 5/14 on EHCF - LGG did ( P = .002 ) . CONCLUSION Fecal calprotectin is elevated in infants with hematochezia and possible allergic colitis . EHCF + LGG result ed in significant improvement of hematochezia and fecal calprotectin compared with the EHCF alone", "Background . Lactobacillus reuteri has been studied for its safety and beneficial effects in infants . This study assessed growth of infants fed a partially hydrolyzed whey formula with L reuteri . Methods . Healthy term infants were r and omized to 1 of 2 formulas ( partially hydrolyzed whey formula with ( PRO ) or without ( CON ) L reuteri from 14 to 112 days of age . Anthropometric measures were assessed at 14 , 28 , 56 , 84 , and 112 days of age . Tolerance records were completed 2 days prior to each visit . Results . A total of 122 subjects completed study per protocol ( 60 PRO , 62 CON ) . No differences were seen in daily weight gain , length , or head circumference . Overall , between groups , there were no significant differences in formula intake , stool frequency , color , consistency , flatulence , frequency of spit-up/vomiting , mood , sleep , or incidence of adverse events . Conclusion . Infants fed probiotic formula had similar growth to infants fed control formula . Both formulas were well tolerated", "IMPORTANCE Infantile colic , gastroesophageal reflux , and constipation are the most common functional gastrointestinal disorders that lead to referral to a pediatrician during the first 6 months of life and are often responsible for hospitalization , feeding changes , use of drugs , parental anxiety , and loss of parental working days with relevant social consequences . OBJECTIVE To investigate whether oral supplementation with Lactobacillus reuteri DSM 17938 during the first 3 months of life can reduce the onset of colic , gastroesophageal reflux , and constipation in term newborns and thereby reduce the socioeconomic impact of these conditions . DESIGN A prospect i ve , multicenter , double-masked , placebo-controlled r and omized clinical trial was performed on term newborns ( age SETTING Parents were asked to record in a structured diary the number of episodes of regurgitation , duration of inconsolable crying ( minutes per day ) , number of evacuations per day , number of visits to pediatricians , feeding changes , hospitalizations , visits to a pediatric emergency department for a perceived health emergency , pharmacologic interventions , and loss of parental working days . PARTICIPANTS In total , 589 infants were r and omly allocated to receive L reuteri DSM 17938 or placebo daily for 90 days . INTERVENTIONS Prophylactic use of probiotic . MAIN OUTCOMES AND MEASURES Reduction of daily crying time , regurgitation , and constipation during the first 3 months of life . Cost-benefit analysis of the probiotic supplementation . RESULTS At 3 months of age , the mean duration of crying time ( 38 vs 71 minutes ; P the mean number of regurgitations per day ( 2.9 vs 4.6 ; P the mean number of evacuations per day ( 4.2 vs 3.6 ; P mean savings per patient of € 88 ( US $ 118.71 ) for the family and an additional € 104 ( US $ 140.30 ) for the community . CONCLUSIONS AND RELEVANCE Prophylactic use of L reuteri DSM 17938 during the first 3 months of life reduced the onset of functional gastrointestinal disorders and reduced private and public costs for the management of this condition . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01235884", "The possible role of cows milk intolerance in the aetiology of infant colic was evaluated in 19 babies presenting to their health visitor or general practitioner in one town . Over a three week period a st and ard modified cows milk formula was compared with a soya milk formula on a double blind basis . The duration of colic symptoms was significantly reduced during the week on soya milk ( P less than 0.01 ) , with 11 out of 19 babies fulfilling the diagnostic criteria for cows milk intolerance . Four babies whose symptoms failed to improve either spontaneously or with soya milk were given a hydrolysed protein milk with a positive response in two , confirmed by challenge testing . Thus in 13 out of 19 babies ( 68 % ) the symptoms of infant colic resolved almost completely with dietary change", "Abstract Forty breastfed full-term infants were r and omly , double blind assigned to receive orally Lactobacillus reuteri ( L. reuteri ) DSM 17938 , 5 drops/daily ( 108 colony-forming units ) , for 4 weeks ( n = 20 ) or an identical placebo ( n = 20 ) , starting before third day of life . They underwent basal and final visit to monitor growth parameters and gastrointestinal ( GI ) disease . Parents registered daily : crying minutes , stool frequency and consistency , numbers of regurgitations , adverse events . Secretory IgA ( sIgA ) has been measured in saliva on 28th day . Treated infants demonstrated a reduction in daily regurgitations at the end of treatment ( p = 0.02 ) , three neonates in the placebo group only needed simethicone for GI pain , sIgA level was similar in both groups . R and om casualty produced an unbalanced gender distribution in the groups , but this bias did not affect the results . Therefore , early administration of L. reuteri DSM 17938 result ed beneficial in preventing regurgitation episodes during the first month of life", "Transient lactose intolerance has been identified as a possible causative factor in infant colic . A double-blind r and omised placebo-controlled crossover study to investigate this has been undertaken in 53 babies with symptoms of colic . Pre-incubation of the feed with lactase result ed in breath hydrogen levels and total crying time which were both at least 45 % lower than figures with placebo treatment , in 26 % of the full trial group ( 95 % confidence interval 12.9 % to 44.4 % ) , and in 38 % of compliers ( 95 % confidence interval 18.8 % to 59.4 % ) . The remainder did not respond to the same extent . These findings suggest that infant colic may have a multiple aetiology , and that in a significant number of cases the immediate cause is transient lactose intolerance , in which cases pretreatment of feeds with lactase can result in considerable symptomatic benefits", "Objective : To compare the safety and tolerance of two formulas , supplemented with different probiotic agents , in early infancy . Design : Prospect i ve r and omized placebo-controlled trial . Setting : Clinics of a University Medical Center . Subjects : Full-term healthy infants aged less than 4 months . Intervention : Infants were r and omly assigned for 4 weeks to a st and ard milk-based formula supplemented with either Bifidobacterium lactis ( BB-12 ) , Lactobacillus reuteri ( ATCC 55730 ) or a probiotics-free formula . Measures of Outcome : Growth parameters , daily characteristics of feeding , stooling and behavior , and side effects . Results : Fifty-nine infants , aged 3–65 days , were included . Subjects in all three groups were similar at entry in terms of gestational age , birth weight , sex , growth parameters and breast feeding rate prior to the study . The supplemented formulas were well accepted and did not reveal any adverse effects . A comparison of growth parameters , and variables of feeding , stooling and crying and irritability did not reveal any significant differences between groups . Conclusions : The use of formula supplemented with either Lactobacillus reuteri or Bifidobacterium lactis in early infancy , was safe , well tolerated and did not adversely affect growth , stooling habits or infant behavior", "OBJECTIVE To evaluate the impact of early prebiotic and probiotic intervention on preterm infants ' well-being , crying , growth , and microbiological programming . STUDY DESIGN Ninety-four preterm infants ( gestational age 32 - 36 weeks and birth weight > 1500 g ) r and omized to receive prebiotics ( mixture of galacto-oligosaccharide and polydextrose 1:1 ) , probiotics ( Lactobacillus rhamnosus GG ) , or placebo during the first 2 months of life were followed up for 1 year . Infants were categorized based on the extent of crying and irritability during the first 2 months of life , and their gut microbiota was investigated by fluorescence in situ hybridization ( n = 66 ) and quantitative polymerase chain reaction ( n = 63 ) . RESULTS A total of 27 of 94 infants ( 29 % ) infants were classified as excessive criers , significantly less frequently in the prebiotic and the probiotic groups than in the placebo group ( 19 % vs 19 % vs 47 % , respectively ; P = .02 ) . The placebo group had a higher percentage of Clostridium histolyticum group bacteria in their stools than did the probiotic group ( 13.9 % vs 8.9 % , respectively ; P = .05 ) . There were no adverse events related to either supplementation . CONCLUSIONS Early prebiotic and probiotic supplementation may alleviate symptoms associated with crying and fussing in preterm infants . This original finding may offer new therapeutic and preventive measures for this common disturbance in early life", "Objectives : The aim of this study was to evaluate the efficacy on crying episodes owing to infantile colic of a new infant formula containing partially hydrolysed whey proteins , prebiotic oligosaccharides ( OS ) , with a high β-palmitic acid content . Design : Prospect i ve r and omized controlled study . Setting : Italy . Subjects : Two hundred and sixty-seven formula-fed infants , aged less than 4 months , with infantile colic , were r and omized to receive either the new infant formula ( study treatment ( ST ) ) or a st and ard formula and simethicone ( 6 mg/kg twice a day ) ( control treatment ( CT ) ) . A question naire was given to parents to evaluate for 14 days the daily number of colic episodes and crying time . Results : Out of the 199 infants who completed the study , 96 were treated with the new formula and 103 were not treated . Infants receiving the new formula had a significant decrease in colic episodes after 1 week ( 2.47±1.94 at day 7 vs 5.99±1.84 at the study entry ) compared to infants receiving the CT ( 3.72±1.98 at day 7 vs 5.41±1.88 at the study entry ) ( P the crying episodes were significantly different between the two groups of infants ( 1.76±1.60 in ST vs 3.32±2.06 in CT ) ( P partially hydrolysed formula supplemented with fructo- and galacto-OS induces a reduction of crying episodes in infants with colic after 7 and 14 days when compared with a st and ard formula and simethicone . Sponsorship : The study was supported by funds from Numico , Italy", "Objective To determine whether the probiotic Lactobacillus reuteri DSM 17938 reduces crying or fussing in a broad community based sample of breastfed infants and formula fed infants with colic aged less than 3 months . Design Double blind , placebo controlled r and omised trial . Setting Community based sample ( primary and secondary level care centres ) in Melbourne , Australia . Participants 167 breastfed infants or formula fed infants aged less than 3 months meeting Wessel ’s criteria for crying or fussing : 85 were r and omised to receive probiotic and 82 to receive placebo . Interventions Oral daily L reuteri ( 1 × 108 colony forming units ) versus placebo for one month . Main outcomes measures The primary outcome was daily duration of cry or fuss at 1 month . Secondary outcomes were duration of cry or fuss ; number of cry or fuss episodes ; sleep duration of infant at 7 , 14 , and 21 days , and 1 and 6 months ; maternal mental health ( Edinburgh postnatal depression subscale ) ; family functioning ( paediatric quality of life inventory ) , parent quality adjusted life years ( assessment of quality of life ) at 1 and 6 months ; infant functioning ( paediatric quality of life inventory ) at 6 months ; infant faecal microbiota ( microbial diversity , colonisation with Escherichia coli ) , and calprotectin levels at 1 month . In intention to treat analyses the two groups were compared using regression models adjusted for potential confounders . Results Of 167 infants r and omised from August 2011 to August 2012 , 127 ( 76 % ) were retained to primary outcome ; of these , a subset was analysed for faecal microbial diversity , E coli colonisation , and calprotectin levels . Adherence was high . Mean daily cry or fuss time fell steadily in both groups . At 1 month , the probiotic group cried or fussed 49 minutes more than the placebo group ( 95 % confidence interval 8 to 90 minutes , P=0.02 ) ; this mainly reflected more fussing , especially for formula fed infants . The groups were similar on all secondary outcomes . No study related adverse events occurred . Conclusions L reuteri DSM 17938 did not benefit a community sample of breastfed infants and formula fed infants with colic . These findings differ from previous smaller trials of selected population s and do not support a general recommendation for the use of probiotics to treat colic in infants . Trial registration Current Controlled Trials IS RCT N95287767", "This study found that two casein hydrolysate formulas varying in composition were equally effective in managing colicky symptoms associated with protein sensitivity . Both hydrolysate formulas were associated with a significant , comparable reduction in crying duration and intensity from baseline in 15 of 22 infants with complete data . Subsequent challenge data suggest that the population studied were infants experiencing colicky symptoms due to protein sensitivity . A greater proportion of infants showed a positive reaction ( ≥1.5h of crying/d ) to the protein challenges than the placebo challenge , and crying was rated as more intense during whey and milk protein challenges", "BACKGROUND Newborn infants in modern maternity hospitals are subject to numerous factors that affect normal intestinal colonization -- for example , cesarean delivery and antimicrobial agents . To study the duration of the effect of external factors on intestinal colonization , two groups of infants with different delivery methods were investigated . METHODS The fecal flora of 64 healthy infants was studied prospect ively . Thirty-four infants were delivered vaginally , and 30 by cesarean birth with antibiotic prophylaxis administered to their mothers before the delivery . The fecal flora was cultured on nonselective and selective media in infants 3 to 5 , 10 , 30 , 60 , and 180 days of age . Gastrointestinal signs were recorded daily by the mothers for 2 months . RESULTS The fecal colonization of infants born by cesarean delivery was delayed . Bifidobacterium-like bacteria and Lactobacillus-like bacteria colonization rates reached the rates of vaginally delivered infants at 1 month and 10 days , respectively . Infants born by cesarean delivery were significantly less often colonized with bacteria of the Bacteroides fragilis group than were vaginally delivered infants : At 6 months the rates were 36 % and 76 % , respectively ( p=0.009 ) . The occurrence of gastrointestinal signs did not differ between the study groups . CONCLUSIONS This study shows for the first time that the primary gut flora in infants born by cesarean delivery may be disturbed for up to 6 months after the birth . The clinical relevance of these changes is unknown , and even longer follow-up is needed to establish how long-lasting these alterations of the primary gut flora can be", "OBJECTIVE To determine the effectiveness of whey hydrolysate formula in the treatment of infantile colic in a primary care setting in the Netherl and s. STUDY DESIGN R and omized , double-blind , parallel trial with a 1-week qualification period and a 1-week intervention period . Participants . Forty-three healthy , thriving , formula-fed infants , 3 hours per day on at least 3 days per week . Infants were r and omized to whey hydrolysate formula ( n = 23 ) or st and ard formula ( n = 20 ) . MAIN OUTCOME MEASURE Difference in duration of crying ( minutes per day ) between qualification week and intervention week . RESULTS Analysis according to the intention to treat principle showed a difference in the decrease of crying duration of 63 minutes per day [ 95 % confidence interval : 1 - 127 minutes per day ] in favor of the whey hydrolysate formula . Five infants did not complete the trial . The scope of the study was not sufficient to expect significant differences in the subgroup analyses . CONCLUSIONS An extensively hydrolyzed whey formula is effective in reducing the duration of crying in a primary care setting", " Sixty-six mothers of 66 breast-fed infants with infantile colic were put on a diet free from cow 's milk . The colic disappeared in 35 infants ; it reappeared on at least two challenges ( cow 's milk to mother ) in 23 infants ( 35 % ) . A double-blind crossover trial with cow 's milk whey protein was performed in 16 of these 23 mothers and infants . Six infants had to be taken out of the study for various reasons ; of the remaining ten infants , nine reacted with colic after their mothers ' intake of whey protein-containing capsules . Sequential analysis showed a high correlation between infantile colic in breast-fed infants and their mothers ' consumption of cow 's milk protein . A diet free of cow 's milk is suggested for the mothers as a first trial of treatment of infantile colic in breast-fed infants", "There are several causes of infantile colic . The aim of this study was to evaluate , under controlled conditions , whether bovine whey proteins can elicit symptoms of infantile colic in colicky formula-fed infants . The mean age for entering the study was 6.4 weeks and the mean age for colic debut was 3.7 weeks . In 24 of 27 infants with severe colic , the symptoms disappeared when they were given a cow 's milk-free diet ( Nutramigen ) . These 24 infants were entered into a double-blind crossover study . The infants ( receiving cow 's milk-free diet ) were given the contents of identical capsules with each meal during day 6 . The same procedure was repeated on day 10 . The capsules contained either whey protein powder ( with Nutramigen added ) or human albumin powder ( with Nutramigen added ) . Eighteen infants receiving the whey protein-containing capsules reacted with colic , two infants receiving placebo reacted with colic ( P less than .001 ) , and four infants did not react at all . Crying hours per day for the 24 infants were 5.6 hours for formula-fed infants and 0.7 hour for cow 's milk-free diet-fed infants ( P less than .001 ) . Crying hours per day were 3.2 hours for the infants receiving whey protein capsules and 1.0 hour for those receiving placebo ( P less than .001 ) . In conclusion , bovine whey protein can elicit symptoms of infantile colic in colicky formula-fed infants", " Infants were recruited in four centres in North-West Italy . 138 infants were assessed for eligibility , 113 ones underwent r and omisation and 105 completed the study . Newborns aged less than 10 days of life , with gestational age between 37 and 42 weeks , birth weight from 2,500 to 4,300 g and normal physical examination were recruitable . Premature infants and infants affected by outcomes of perinatal hypoxia or necrotising enterocolitis have been excluded . Patients were r and omly assigned to receive five drops containing Lactobacillus reuteri DSM 17938 ( 108 cfu ) with 400 UI of vitamin D3 or only 400 UI of vitamin D3 daily . The primary endpoints concern the administration of pain relieving agents ( cimetropium bromide at least three times per week or simethicone at least five times per week ) from baseline to 12 weeks . Additional analyses were done on the percentage of infants that switched from an exclusive breastfeeding to a partial or exclusive formula feeding from baseline to 12 weeks . Data concerning the number of calls to the paediatricians and the number of visits at paediatricians ' ambulatories due to infantile colic have been collected by paediatrician and analysed . Comparing the two groups , the relative risk was 0.04 ( 95 % confidence interval (CI)=0.01 - 0.31 ) for cimetropium bromide , 0.24 ( 95 % CI=0.14 - 0.41 ) for simethicone and 0.37 ( 95 % CI=0.17 - 0.80 ) for the administration of infant formula , showing a protective action of L. reuteri . The treatment group showed a lower number of paediatric consultations related to episodes of infant colic than the control group ( P DSM 17938 supplementation at the tested dosage could reduce parental discomfort due to infantile colic . The consumption of this probiotic is associated with a reduction of paediatric consultations for infantile colic , as well as use of pain relieving agents and of infant formula", "BACKGROUND A mixture of neutral prebiotic oligosaccharides has been shown to reduce the incidence of atopic dermatitis ( AD ) and allergy associated symptoms during the first 2 years of life . OBJECTIVE To evaluate if this protective effect against allergy lasted beyond the intervention period until 5 y of age . METHODS In a prospect i ve , double blind , placebo-controlled fashion , healthy term infants at risk of atopy were fed either a prebiotic-supplemented ( 0.8 g/100 ml scGOS/lcFOS ) or placebo-supplemented ( 0.8 g/100 ml maltodextrin ) hypoallergenic formula during the first 6 mo of life . Following this intervention period , follow-up continued until 5 y of life . The present study evaluated ( i ) the cumulative incidence of allergic manifestations during 5 y , and ( ii ) the prevalence of allergic and persistent allergic manifestations at 5 y. Monitored allergic manifestations were AD , recurrent wheezing , allergic rhinoconjunctivitis and urticaria . RESULTS Ninety-two children ( 50 in placebo group , 42 in intervention group ) completed the 5-y follow-up . The 5-y cumulative incidences of any allergic manifestation and atopic dermatitis were significantly lower in the scGOS/lcFOS group ( 30.9 , 19.1 % , respectively ) compared to placebo group ( 66 , 38 % , respectively ) ( p incidence of allergic rhinoconjunctivitis , and allergic urticaria ( 4.8 vs 16 % for both manifestations , p=0.08 ) . There was no difference in the cumulative incidence of recurrent wheezing . With regard to the prevalences at 5 y , intervention group had significantly lower prevalence of any persistent allergic manifestation and rhinoconjunctivitis ( 4.8 , 2.4 % , respectively ) compared to placebo ( 26 , 14 % , respectively ) ( p Prevalence of persistent AD tended to be lower in the intervention group ( 2.4 vs 12 % , p= 0.09 ) . Although intervention group had 75 % reduction in the prevalence of persistent wheezing ( 4.8 vs 14 % ) , no significance was shown . CONCLUSION Oligosaccharide prebiotics ( scGOS/lcFOS ) , when started early in life have a protective effect against allergic manifestations in high risk infants . The protection lasts beyond infancy until 5 y of life , for AD and allergic rhinoconjunctivitis . Long-term follow-up studies in larger population s are warranted to evaluate the potential preventive effect of this mixture on asthma", "OBJECTIVE . Live probiotic bacteria and dietary prebiotic oligosaccharides ( together termed synbiotics ) increasingly are being used in infancy , but evidence of long-term safety is lacking . In a r and omized , placebo-controlled , double-blind trial , we studied the safety and long-term effects of feeding synbiotics to newborn infants . METHODS . Between November 2000 and March 2003 , pregnant mothers carrying infants at high risk for allergy were r and omly assigned to receive a mixture of 4 probiotic species ( Lactobacillus rhamnosus GG and LC705 , Bifidobacterium breve Bb99 , and Propionibacterium freudenreichii ssp shermanii ) or a placebo for 4 weeks before delivery . Their infants received the same probiotics with 0.8 g of galactooligosaccharides , or a placebo , daily for 6 months after birth . Safety data were obtained from clinical examinations and interviews at follow-up visits at ages 3 , 6 , and 24 months and from question naires at ages 3 , 6 , 12 , and 24 months . Growth data were collected at each time point . RESULTS . Of the 1018 eligible infants , 925 completed the 2-year follow-up assessment . Infants in both groups grew normally . We observed no difference in neonatal morbidity , feeding-related behaviors ( such as infantile colic ) , or serious adverse events between the study groups . During the 6-month intervention , antibiotics were prescribed less often in the synbiotic group than in the placebo group ( 23 % vs 28 % ) . Throughout the follow-up period , respiratory infections occurred less frequently in the synbiotic group ( geometric mean : 3.7 vs 4.2 infections ) . CONCLUSION . Feeding synbiotics to newborn infants was safe and seemed to increase resistance to respiratory infections during the first 2 years of life", "BACKGROUND The effect of diet change in 38 bottle-fed and 77 breast-fed \" colicky \" infants , referred from community-based pediatric facilities was studied over a 1-week period in a double-blind ( within each feeding mode ) , r and omized , placebo-controlled trial . METHODS Bottle-fed infants were assigned to either casein hydrolysate or cow 's milk formula . All mothers of breast-fed infants were started on an artificial color-free , preservative-free , additive-free diet and also r and omized to an active low allergen diet ( milk- , egg- , wheat- , nut-free ) or a control diet . RESULTS The response to diet was assessed on day 1 and day 8 with the use of a previously vali date d infant distress chart on which parents recorded distress levels . If successful outcome was defined as a reduction in distress of 25 % or more , after adjusting for age and feeding mode , infants on active diet had a significantly higher rate of improvement than those on the control diet ( odds ratio , 2.32 ; 95 % confidence interval , 1.07 - 5.0 ; p = 0.03 ) . Analysis of the day 8 to day 1 distress ratio , again adjusted for age and feeding mode , showed that infants on the active diet had distress reduced by 39 % ( 95 % confidence interval , 26 - 50 ) compared with 16 % ( 95 % confidence interval , 0 - 30 ) for those on the control diet ( p = 0.012 ) . CONCLUSION The results suggest a period of dietary modification with a low allergen diet and appropriate nutritional support should be considered in healthy infants with colic", "The role of cow 's milk in infantile colic in formula-fed infants was estimated in a double-blind study . Sixty colicky infants were given a cow 's milk-containing formula ( Enfamil ) and a cow 's milk-free formula based on soy ( ProSobee ) . Eleven infants ( 18 % ) were free of symptoms while receiving soy formula . Symptoms of 32 infants ( 53 % ) were unchanged or worse when they were fed cow 's milk formula and soy formula , but symptoms disappeared when they were fed a formula containing hydrolyzed casein ( Nutramigen ) . Symptoms of 17 infants ( 29 % ) could not be related to the diet ; these infants were permitted to continue on a cow 's milk-based formula . A challenge with cow 's milk-based formula after one month ( at approximately age 3 months ) produced symptoms of infantile colic in 22 infants ( 36 % ) . At age 6 months , a challenge with cow 's milk was positive in 11 infants ( 18 % ) with epidermal and gastrointestinal symptoms . Eight infants ( 13 % ) at 12 months of age and five infants ( 8 % ) at 16 months of age were still intolerant to cow 's milk . Cow 's milk seems to be a major cause of infantile colic in formula-fed infants . A dietary treatment is suggested for moderate or severe forms of the colic . Cow 's milk protein intolerance is common later in infancy in these infants", "Infant Distress and Development of Functional Gastrointestinal Disorders in Childhood : Is There a Connection ? One infant in 4 manifests with abundant crying , fussing , or colic cry and is brought for medical evaluation during the first months of life.1 Concomitantly , excessive antigen uptake and bacterial translocation ensue across the immature gut barrier.2 Not surprisingly , infant crying has been related to food allergy3 and aberrant gut microbiota composition4 and these have , in turn , been linked to functional gastrointestinal disorders (FGIDs).5 We hypothesized that colic crying is associated with FGIDs later in childhood", "BACKGROUND The etiology of infant colic remains unknown , despite an abundance of research on the topic . OBJECTIVE To determine whether breastfeeding has a protective effect in colic 's development . DESIGN A prospect i ve cohort study of 856 mother-infant dyads . Eligible participants included English-speaking adult residents of a region in Ontario , who gave birth , at term , to a live singleton whose birth weight was appropriate for gestational age . Self-administered question naires , mailed to mothers at 1 and 6 weeks post partum , requested information on several infant and maternal factors , including source of infant nutrition ( exclusively breastfed , complementary fed , and exclusively formula fed ) . Cases of colic were identified by applying modified Wessel criteria to data recorded in the Barr Baby Day Diary or by interpreting responses to the Ames Cry Score . MAIN OUTCOME MEASURES Prevalence of colic among breastfed , formula-fed , and complementary-fed infants ; and adjusted odds ratios ( AORs ) reflecting the prevalence of colic among formula- and complementary-fed infants relative to those who were breastfed . RESULTS Of 856 mothers , 733 ( 86 % ) completed the first question naire and 617 ( 72 % ) completed the second question naire . Overall , the prevalence of colic at 6 weeks was 24 % . No association was seen between the source of infant nutrition and colic 's development . In multivariate analyses , higher levels of maternal trait anxiety ( AOR , 1.22 ; 95 % confidence interval [ CI ] , 0.96 - 1.54 ) , maternal alcohol consumption at 6 weeks ( AOR , 1.57 ; 95 % CI , 1.03 - 2.40 ) , and shift work during pregnancy ( AOR , 1.27 ; 95 % CI , 0.73 - 2.21 ) were associated with an increased likelihood of colic , after controlling for feeding method , maternal age , and parity . In these same analyses , being married or having a common-law partner ( AOR , 0.30 ; 95 % CI , 0.10 - 0.87 ) and being employed full-time during pregnancy ( AOR , 0.60 ; 95 % CI , 0.32 - 1.14 ) were associated with a reduced likelihood of colic . CONCLUSIONS Breastfeeding did not have a protective effect on the development of colic . Although colic was statistically associated with several variables , including preexisting maternal anxiety , much of colic 's etiology remains unexplained", "BACKGROUND The increase in allergic diseases is attributed to a relative lack of microbial stimulation of the infantile gut immune system . Probiotics , live health-promoting microbes , might offer such stimulation . OBJECTIVE We studied the effect of a mixture of 4 probiotic bacterial strains along with prebiotic galacto-oligosaccharides in preventing allergic diseases . METHODS We r and omized 1223 pregnant women carrying high-risk children to use a probiotic preparation or a placebo for 2 to 4 weeks before delivery . Their infants received the same probiotics plus galacto-oligosaccharides ( n = 461 ) or a placebo ( n = 464 ) for 6 months . At 2 years , we evaluated the cumulative incidence of allergic diseases ( food allergy , eczema , asthma , and allergic rhinitis ) and IgE sensitization ( positive skin prick test response or serum antigen-specific IgE level > 0.7 kU/L ) . Fecal bacteria were analyzed during treatment and at age 2 years . RESULTS Probiotic treatment compared with placebo showed no effect on the cumulative incidence of allergic diseases but tended to reduce IgE-associated ( atopic ) diseases ( odds ratio [ OR ] , 0.71 ; 95 % CI , 0.50 - 1.00 ; P = .052 ) . Probiotic treatment reduced eczema ( OR , 0.74 ; 95 % CI , 0.55 - 0.98 ; P = .035 ) and atopic eczema ( OR , 0.66 ; 95 % CI , 0.46 - 0.95 ; P = .025 ) . Lactobacilli and bifidobacteria more frequently ( P treatment showed no effect on the incidence of all allergic diseases by age 2 years but significantly prevented eczema and especially atopic eczema . The results suggest an inverse association between atopic diseases and colonization of the gut by probiotics . CLINICAL IMPLICATION S The prevention of atopic eczema in high-risk infants is possible by modulating the infant 's gut microbiota with probiotics and prebiotics", "OBJECTIVE To investigate the effect of dietary supplementation with a probiotic on feeding tolerance and gastrointestinal motility in healthy formula-fed preterm infants . STUDY DESIGN Thirty preterm newborns were enrolled ; 10 were exclusively breast-fed , and the remaining 20 were r and omly assigned in a double-blind manner to receive either Lactobacillus reuteri ATCC 55730 ( at dose of 1 x 10(8 ) colony forming units a day ) or placebo for 30 days . Clinical symptoms of gastrointestinal function ( regurgitation , vomiting , inconsolable crying , and evacuation ) and physiological variables ( gastric electrical activity and emptying ) were recorded before and after the dietary intervention . RESULTS Body weight gains per day were similar for the 3 groups , and no adverse events were recorded . Newborns receiving probiotics showed a significant decrease in regurgitation and mean daily crying time and a larger number of stools compared with those given placebo . Gastric emptying rate was significantly increased , and fasting antral area was significantly reduced in both the newborns receiving L. reuteri and breast-fed newborns compared with placebo . CONCLUSIONS Our results suggest a useful role for L. reuteri supplementation in improving feeding tolerance and gut function in formula-fed preterm newborns", "OBJECTIVE : To test the efficacy of Lactobacillus reuteri on infantile colic and to evaluate its relationship to the gut microbiota . STUDY DESIGN : Fifty exclusively breastfed colicky infants , diagnosed according to modified Wessel 's criteria , were r and omly assigned to receive either L reuteri DSM 17 938 ( 108 colony-forming units ) or placebo daily for 21 days . Parental question naires monitored daily crying time and adverse effects . Stool sample s were collected for microbiologic analysis . RESULTS : Forty-six infants ( L reuteri group : 25 ; placebo group : 21 ) completed the trial . Daily crying times in minutes/day ( median [ interquartile range ] ) were 370 ( 120 ) vs 300 ( 150 ) ( P = .127 ) on day 0 and 35.0 ( 85 ) vs 90.0 ( 148 ) ( P = .022 ) on day 21 , in the L reuteri and placebo groups , respectively . Responders ( 50 % reduction in crying time from baseline ) were significantly higher in the L reuteri group versus placebo group on days 7 ( 20 vs 8 ; P = .006 ) , 14 ( 24 vs 13 ; P = .007 ) , and 21 ( 24 vs 15 ; P = .036 ) . During the study , there was a significant increase in fecal lactobacilli ( P = .002 ) and a reduction in fecal Escherichia coli and ammonia in the L reuteri group only ( P = .001 ) . There were no differences in weight gain , stooling frequency , or incidence of constipation or regurgitation between groups , and no adverse events related to the supplementation were observed . CONCLUSION : L. reuteri DSM 17 938 at a dose of 108 colony-forming units per day in early breastfed infants improved symptoms of infantile colic and was well tolerated and safe . Gut microbiota changes induced by the probiotic could be involved in the observed clinical improvement" ]	41188dd0-06ff-11f0-808a-c43d1ab1c353
Moderate-to-vigorous-intensity physical activity ( MVPA ) is important for childhood obesity prevention and treatment , yet declines with age . Timing and magnitude of the decline in MVPA in children and adolescents are unclear but important for informing effective obesity intervention development . This systematic review aim ed to determine and compare the year-to-year changes in MVPA among children and adolescents . Longitudinal studies were identified by search ing 10 relevant data bases up to December 2018 . Studies were eligible for inclusion if they reported accelerometer-assessed MVPA ( min day-1 ) separately for boys and girls and had follow-up duration of at least 1 year . After screening 9,232 studies , 52 were included representing 22,091 aged 3 to 18 year olds ( boys=8,857 ; girls=13,234 ) . Pooled- analysis of the relative change in MVPA per year showed a decline of -3.4 % ( 95 % CI , -5.9 to -0.9 ) in boys and -5.3 % ( 95 % CI , -7.6 to -3.1 ) in girls , across all age groups . There were notable declines in MVPA at age 9 for both boys ( -7.8 % , 95 % CI , -11.2 to -4.4 ) and girls ( -10.2 % , 95 % CI , -14.2 to -6.3 ) . The relative decline in MVPA affects both sexes from an early age ; however , it is greater among girls . Interventions to promote MVPA should start before adolescence	[ "Background Exergaming has been proposed as an innovative method for physical activity promotion . However , large effectiveness studies are rare . In January 2011 , dance mat systems were introduced in secondary schools in two districts in Engl and with the aim of promoting an innovative opportunity for physical activity . The aim of this natural experiment was to examine the effect of introducing the dance mat exergaming systems on physical activity and health-related outcomes in 11–13 year old students using a non-r and omised controlled design and mixed methods . Methods Participants were recruited from five schools in intervention districts ( n = 280 ) and two schools in neighbouring control districts ( n = 217 ) . Data on physical activity ( accelerometer ) , anthropometrics ( weight , BMI and percentage of body fat ) , aerobic fitness ( 20-m multistage shuttle run test ) , health-related quality of life ( Kidscreen question naire ) , self-efficacy ( children ’s physical activity self-efficacy survey ) , school attendance , focus groups with children and interviews with teachers were collected at baseline and approximately 12 months follow-up . Results There was a negative intervention effect on total physical activity ( -65.4 cpm CI : -12.6 to -4.7 ) , and light and sedentary physical activity when represented as a percentage of wear time ( Light : -2.3 % CI : -4.5 to 0.2 ; Sedentary : 3.3 % CI : 0.7 to 5.9 ) . However , compliance with accelerometers at follow-up was poor . There was a significant positive intervention effect on weight ( -1.7 kg , 95 % CI : -2.9 to -0.4 ) , BMI ( -0.9 kg/m2 , 95 % CI : -1.3 to -0.4 ) and percentage of body fat ( -2.2 % , 95 % CI : -4.2 to -0.2 ) . There was also evidence of improvement in some health-related quality of life parameters : psychological well-being ( 2.5 , 95 % CI : 0.1 to 4.8 ) and autonomy and parent relation ( 4.2 , 95 % CI : 1.4 to 7.0 ) . Conclusions The implementation of a dance mat exergaming scheme was associated with improvement in anthropometric measurements and parameters of health-related quality of life . However , the mechanisms of these benefits are unclear as there was insufficient data from physical activity to draw robust conclusions . Qualitative findings suggest that there was declining support for the initiative over time , meaning that potential benefits may not have been achieved", "INTRODUCTION Few interventions have been successful in reducing the physical activity decline typically observed among adolescents . The aim of this paper is to report the 24-month effectiveness of a multicomponent school-based intervention ( Physical Activity 4 Everyone ) in reducing the decline in moderate to vigorous physical activity ( MVPA ) among secondary school students in disadvantaged areas of New South Wales , Australia . STUDY DESIGN A cluster RCT was conducted in five intervention and five control schools with follow-up measures taken at 24 months post-r and omization . SETTING / PARTICIPANTS The trial was undertaken within secondary schools located in disadvantaged communities in New South Wales , Australia . INTERVENTION A multicomponent school-based intervention based on the Health Promoting Schools Framework was implemented . The intervention consisted of seven physical activity promotion strategies that targeted the curriculum ( teaching strategies to increase physical activity in physical education lessons , student physical activity plans , and modification of school sport program ) ; school environment ( recess/lunchtime activities , school physical activity policy ) ; parents ( parent newsletters ) ; and community ( community physical activity provider promotion ) . Six additional strategies supported school implementation of the physical activity intervention strategies . MAIN OUTCOME MEASURE Minutes per day spent in MVPA , objective ly measured by accelerometer . RESULTS Participants ( N=1,150 , 49 % male ) were a cohort of students aged 12 years ( Grade 7 ) at baseline ( March-June 2012 ) and 14 years ( Grade 9 ) at follow-up ( March-July 2014 ) . At 24-month follow-up , there were significant effects in favor of the intervention group for daily minutes of MVPA . The adjusted mean difference in change in daily MVPA between groups was 7.0 minutes ( 95 % CI=2.7 , 11.4 , p adolescents ' minutes of MVPA , suggesting that implementation of the intervention by disadvantaged schools has the potential to slow the decline in physical activity . TRIAL REGISTRATION Australian New Zeal and Clinical Trials Registry ACTRN12612000382875", "Background Although school-based interventions to promote physical activity in adolescents have been suggested in several recent review s , questions have been raised regarding the effects of the strategies and the methodology applied and for whom the interventions are effective . The aim of the present study was to investigate effects of a school-based intervention program : the HEalth in Adolescents ( HEIA ) study , on change in physical activity , and furthermore , to explore whether potential effects varied by gender , weight status , initial physical activity level and parental education level . Methods This was a cluster r and omized controlled 20 month intervention study which included 700 11-year-olds . Main outcome -variable was mean count per minute ( cpm ) derived from ActiGraph accelerometers ( Model 7164/GT1 M ) . Weight and height were measured objective ly . Adolescents reported their pubertal status in a question naire and parents reported their education level on the consent form . Linear mixed models were used to test intervention effects and to account for the clustering effect of sampling by school . Results The present study showed an intervention effect on overall physical activity at the level of p = 0.05 with a net effect of 50 cpm increase from baseline to post intervention in favour of the intervention group ( 95 % CI −0.4 , 100 ) . Subgroup analyses showed that the effect appeared to be more profound among girls ( Est 65 cpm , CI 5 , 124 , p = 0.03 ) and among participants in the low-activity group ( Est 92 cpm , CI 41 , 142 , p affected physical activity among the normal weight group more positively than among the overweight , and participants with parents having 13–16 years of education more positively than participants with parents having either a lower or higher number of years of education . The intervention seemed to succeed in reducing time spent sedentary among girls but not among boys . Conclusions A comprehensive but feasible , multi-component school-based intervention can affect physical activity patterns in adolescents by increasing overall physical activity . This intervention effect seemed to be more profound in girls than boys , low-active adolescents compared to high-active adolescents , participants with normal weight compared to the overweight , and for participants with parents of middle education level as opposed to those with high and low education levels , respectively . An implementation of the HEIA intervention components in the school system may have a beneficial effect on public health by increasing overall physical activity among adolescents and possibly among girls and low-active adolescents in particular", "The aims of this study were to investigate whether physical activity ( PA ) and sedentary time ( ST ) in 9- and 15-year-olds differed between 2005 - 2006 and 2011 - 2012 ( secular change ) , and to investigate changes in PA and ST from age 9 to 15 ( longitudinal change ) . In 2005 - 2006 , we invited nationally representative sample s of Norwegian 9- ( n=1470 ) and 15-year-olds ( n=1348 ) to participate . In 2011 - 2012 , we invited a new nationally representative sample of 9-year-olds ( n=1945 ) , whereas 15-year-olds ( n=1759 ) were invited to participate either based on previous participation in 2005 - 2006 or from a r and om sample of schools . We assessed PA and ST objective ly using accelerometers . In 2011 - 2012 , both 9- and 15-year-olds spent more time sedentary ( ≥35.7 min/d , P in light PA ( ≥35.2 min/d , P in moderate-to-vigorous PA ( MVPA ) ( 4.2 min/d , P=.041 ) . In both age groups , the proportion accumulating an average of 60 min/d of MVPA did not differ between the two cohorts . From age 9 to 15 , girls and boys decreased their time spent in LPA ( ≥106.7 min/d , P and in MVPA ( ≥20.8 min/d , P period , ST increased by a mean of > 2 h/d ( P in PA from 2005 - 2006 to 2011 - 2012 among 9- and 15-year-olds , and a large decline in PA in the participants followed longitudinally from age 9 to 15 years", "Background Globally , adolescent girls ’ physical activity ( PA ) levels are low . The ‘ Girls Active ’ secondary school-based programme , developed by the Youth Sport Trust , aims to increase PA in adolescent girls . This paper explores the effectiveness of the ‘ Girls Active ’ school-based PA programme . Methods A r and om sample of girls aged 11–14 from 20 secondary schools ( Midl and s , UK ) participated in a two-arm cluster r and omised controlled trial . Ten schools received Girls Active and 10 continued with usual practice . Measurements were taken at baseline , seven- and 14-month follow-up . Primary outcome : wrist-worn accelerometer measured moderate- to vigorous-intensity PA ( MVPA ) . Secondary outcomes : overall PA , light PA , sedentary time , body composition , and psychosocial outcomes . Generalised estimating equations , adjusted for school cluster and potential confounders , were used and A priori subgroup analysis was undertaken . Micro-costing and cost-consequence analyses were conducted using bespoke collection methods on programme delivery information . Outcomes for the cost-consequence analysis were health related quality of life measured by the Child Health Utility-9D and service use . Results Overall , 1752 pupils participated , 1211 ( 69.1 % ) provided valid 14-month accelerometer data . No difference in MVPA ( mins/day ; 95 % confidence intervals ) was found at 14 months ( 1.7 ; -0.8 to 4.3 ) , there was at seven months ( 2.4 ; 0.1 to 4.7 ) . Subgroup analyses showed significant intervention effects on 14-month in larger schools ( 3.9 ; 1.39 to 6.09 ) and in White Europeans ( 3.1 ; 0.60 to 6.02 ) and in early maturers ( 5.1 ; 1.69 to 8.48 ) at seven months . The control group did better in smaller schools at 14-months ( -4.38 ; -7.34 to -1.41 ) . Significant group differences were found in 14-month identified motivation ( -0.09 ; -0.18 to -0.01 ) and at seven months in : overall PA ( 1.39 mg/day ; 0.1 to 2.2 ) , after-school sedentary time ( -4.7 ; -8.9 to -0.6 ) , whole day ( 5.7 ; 1.0 to 10.5 ) and school day ( 4.5 ; 0.25 to 8.75 ) light PA , self-esteem . Small , statistically significant , differences in some psychosocial variables favoured control schools . Micro-costing demonstrated that delivering the programme result ed in a range of time and financial costs at each school . Cost-consequence analysis demonstrated no effect of the programme for health related quality of life or service use . Conclusions Compared with usual practice , ‘ Girls Active ’ did not affect 14-month MVPA.Trial registration IS RCT", "Observational longitudinal research is particularly useful for assessing etiology and prognosis and for providing evidence for clinical decision making . However , there are no structured reporting requirements for studies of this design to assist authors , editors , and readers . The authors developed and tested a checklist of criteria related to threats to the internal and external validity of observational longitudinal studies . The checklist criteria concerned recruitment , data collection , biases , and data analysis and descriptive issues relevant to study rationale , study population , and generalizability . Two raters independently assessed 49 r and omly selected articles describing stroke research published from 1999 to 2003 in six journals : American Journal of Epidemiology , Journal of Epidemiology and Community Health , Stroke , Annals of Neurology , Archives of Physical Medicine and Rehabilitation , and American Journal of Physical Medicine and Rehabilitation . On average , 17 of the 33 checklist criteria were reported . Criteria describing the study design were better reported than those related to internal validity . No relation was found between study type ( etiologic or prognostic ) or word count and quality of reporting . A flow diagram for summarizing participant flow through a study was developed . Editors and authors should consider using a checklist and flow diagram when reporting on observational longitudinal research", "Objective To examine whether physical activity ( PA ) and sedentary time ( ST ) in primary school-aged children are associated with adiposity at the start of secondary school , and whether these associations differ by sex or ethnic group . Design Nationally representative prospect i ve cohort study . Setting Children born across the UK , between 2000 and 2002 . Participants 6497 singleton children . Outcome measures Measures of adiposity ( body mass index ( BMI ) , fat mass index ( FMI ) and fat free mass index (FFMI))—obtained at 7 and 11 years . Explanatory measures Total daily PA ( mean counts per minute ( cpm ) ) ; minutes of moderate-to-vigorous PA ( MVPA ) ; and ST . All assessed at 7 years using accelerometers . Results In cross-sectional analyses , total PA was inversely associated with FMI ( 3.7 % ( 95 % CI 2.7 % to 4.7 % ) reduction per 150 cpm increase ) , as was MVPA ( 4.2 % ( CI 3.2 % to 5.2 % ) reduction per 20 min/day increase ) . Associations were stronger in black and South Asian ethnic groups . Total PA and MVPA were not associated with FFMI . ST was positively associated with FMI ( 1.3 % ( CI 0.2 % to 2.3 % ) increase per 50 min/day increase ) and inversely associated with FFMI ( 0.5 % ( CI 0.2 % to 0.7 % ) reduction per 50 min/day increase ) . Longitudinally , MVPA at age 7 years remained inversely associated with FMI at age 11 years ( 1.5 % ( CI 0.4 % to 2.6 % ) reduction per 20 min/day increase ) . No association was found between total PA and ST and any of the later adiposity measures . Conclusions 7-year-old children who are more physically active are less likely to be obese at that age and at age 11 years . These associations were particularly evident in children from black or South Asian ethnicity at age 7 years and in boys at age 11 years . Measurements of fat mass provide valuable insights into ethnic differences in associations between adiposity and activity", "Background The aim of this study was to examine the effectiveness and cost of an after-school dance intervention at increasing the physical activity levels of Year 7 girls ( age 11–12 ) . Methods A cluster r and omised controlled trial was conducted in 18 secondary schools . Participants were Year 7 girls attending a study school . The Bristol Girls Dance Project ( BGDP ) intervention consisted of up to forty , 75-minute dance sessions delivered in the period immediately after school by experienced dance instructors over 20-weeks . The pre-specified primary outcome was accelerometer assessed mean minutes of weekday moderate to vigorous physical activity ( MVPA ) at time 2 ( 52 weeks are T0 baseline assessment s ) . Secondary outcomes included accelerometer assessed mean minutes of weekday MVPA at time 1 ( while the intervention was still running ) and psychosocial outcomes . Intervention costs were assessed . Results 571 girls participated . Valid accelerometer data were collected from 549 girls at baseline with 508 girls providing valid accelerometer data at baseline and time 2 . There were no differences between the intervention and control group for accelerometer assessed physical activity at either time 1 or time 2 . Only one third of the girls in the intervention arm met the pre-set adherence criteria of attending two thirds of the dance sessions that were available to them . Instrumental variable regression analyses using complier average causal effects provided no evidence of a difference between girls who attended the sessions and the control group . The average cost of the intervention was £ 73 per girl , which was reduced to £ 63 when dance instructor travel expenses were excluded . Conclusion This trial showed no evidence that an after-school dance programme can increase the physical activity of Year 7 girls . The trial highlighted the difficulty encountered in maintaining attendance in physical activity programmes delivered in secondary schools . There is a need to find new ways to help adolescent girls to be physically active via identifying ways to support and encourage sustained engagement in physical activity over the life course . Trial registration IS RCT", "Background Physical activity ( PA ) in children has declined in recent decades , highlighting the need for effective intervention programs for school-aged children . The main objective of this study was to assess to what extent PA during and after school hours changed among children who received a progressive two-year long intervention vs. that of children who only received general curriculum-based PA . Methods A cluster r and omized intervention study was conducted and six elementary schools r and omly assigned to serve as control- or intervention schools . All children attending second grade ( mean age = 7.4 years - born in 1999 ) were invited to participate in the fall of 2006 ( N = 320 , 82 % participated ) , again in 2007 ( midpoint ) and 2008 ( end of intervention ) . The intervention consisted of multi-component PA-intervention during school hours and was conducted by teachers at each intervention school . PA was assessed by means of accelerometers and subjectively at the intervention schools via teachers ' PA log-books . Results There was no difference in PA intensity ( minutes of moderate-to-vigorous physical activity - min of MVPA ) between the two study groups at baseline , but children in the intervention schools were more physically active at moderate-to-vigorous intensity compared to those in control schools after one year of intervention ( mean difference of MVPAlog-minutes : 0.61 , 95%CI : 0.02 , 1.20 , p = 0.04 ) . Moreover , the model for minutes of MVPA during school hours , showed a significant three-way interaction between time at mid-point , group and gender ( mean difference of MVPAlog-minutes : 1.06 , 95%CI : 0.15 , 1.97 , p = .02 ) , indicating a significantly greater increase among the boys in the intervention schools compared to girls . No difference in PA was detected between the study groups at the end of the study period after two years of intervention . Conclusions The results suggest that the objective of increasing PA at school was met after one year of intervention , and it was more pronounced among boys . The lack of increase at the end of the study period suggested that any increase in PA during school may highly depend on both motivation and training of general teachers . Boys may respond better to PA interventions such as the one described in this study", "Objectives To study correlates of change in BMI percentile and body fat among adolescent girls Design and Methods A longitudinal prospect i ve study following 265 girls from the Trial of Activity for Adolescent Girls ( TAAG ) cohort measured in 8th grade and during 10 and 11th grade or 11th and 12th grade . Twice during 2009 - 2011 girls wore an accelerometer and completed a food frequency question naire and 7-day diary documenting trips and food eaten away from home and school . Physical activity , BMI , and percent body fat were objective ly measured at each time point . Results Moderate to vigorous physical activity ( MVPA ) declined , but was not independently associated with changes in BMI percentile . Increased vigorous physical activity was associated with reductions in body fat . Diet was associated with both changes in BMI percentile and body fat . Girls who increased the percentage of caloric intake from snacks and desserts reduced their BMI percentile and body fat . Conclusions Some relationships between energy balance behaviors and BMI and body composition were counter-intuitive . While it is plausible that vigorous activity would result in reductions of body fat , until more accurate methods are devised to measure diet , the precise contribution of dietary composition to health will be difficult to assess", "Objective To establish in children whether inactivity is the cause of fatness or fatness the cause of inactivity . Design A non-intervention prospect i ve cohort study examining children annually from 7 to 10 years . Baseline versus change to follow-up associations were used to examine the direction of causality . Setting Plymouth , Engl and . Participants 202 children ( 53 % boys , 25 % overweight/obese ) recruited from 40 Plymouth primary schools as part of the EarlyBird study . Main outcome measures Physical activity ( PA ) was measured using Actigraph accelerometers . The children wore the accelerometers for 7 consecutive days at each annual time point . Two components of PA were analysed : the total volume of PA and the time spent at moderate and vigorous intensities . Body fat per cent ( BF% ) was measured annually by dual energy x ray absorptiometry . Results BF% was predictive of changes in PA over the following 3 years , but PA levels were not predictive of subsequent changes in BF% over the same follow-up period . Accordingly , a 10 % higher BF% at age 7 years predicted a relative decrease in daily moderate and vigorous intensities of 4 min from age 7 to 10 years ( r=−0.17 , p=0.02 ) , yet more PA at 7 years did not predict a relative decrease in BF% between 7 and 10 years ( r=−0.01 , p=0.8 ) . Conclusions Physical inactivity appears to be the result of fatness rather than its cause . This reverse causality may explain why attempts to tackle childhood obesity by promoting PA have been largely unsuccessful", "Background : Physical activity ( PA ) and sedentary time ( SED ) have both been suggested as potential risk factors for adiposity in children . However , there is paucity of data examining the temporal associations between these variables . Objective : This study aim ed to analyze the cross-sectional and prospect i ve associations between PA , SED and body composition in children . Methods : A total of 510 children ( age at baseline 10.1±0.8 , age at follow-up 11.8±0.9 ) from six Portuguese schools from the Oeiras Municipality participated in this study . PA and SED were measured by accelerometry and trunk fat mass ( TFM ) and body fat mass ( BFM ) were measured by dual energy X-ray absorptiometry . Fat mass index ( FMI ) was calculated as BFM divided by height squared . Several regression models adjusted for age , sex , maturity status , follow-up duration , baseline levels of the outcome variable and SED or moderate to vigorous PA ( MVPA ) were performed . Results : MVPA ( min per day ) was cross-sectionally inversely associated with adiposity indexes ( FMI , TFM and BFM ) . Adiposity indexes were inversely associated with time in MVPA . In prospect i ve analyses , MVPA was associated with a lower levels of FMI ( β=−0.37 , 95 % confidence interval ( CI ) : −0.49 to −0.26 , P TFM ( β=−0.20 , 95 % CI : −0.29 to −0.10 , P and BFM ( β=−0.37 , 95 % CI : −0.49 to −0.26 , P outcome variables MVPA remained a significant predictor of lower adiposity indexes ( FMI : β=−0.09 , 95 % CI : −0.16 to −0.01 , P 0.00 , P Adiposity was not associated with MVPA when modeled as the exposure in prospect i ve analyses . SED was not related with adiposity indexes , except for the relationship with FMI . Conclusions : In cross-sectional and prospect i ve analyses , MVPA is associated with lower adiposity independent of covariates and SED . Results suggest that promoting MVPA is important for preventing gain in adiposity in healthy children", "Objective : To determine if time spent in objective ly measured sedentary behavior is associated with a change in body mass index ( BMI ) between ages 9 and 15 years , adjusting for moderate-to-vigorous physical activity ( MVPA ) . Design : Prospect i ve observational study of children at ages 9 ( 2000 ) , 11 ( 2002 ) , 12 ( 2003 ) and 15 years ( 2006 ) . Longitudinal quantile regression was used to model the influence of predictors on changes at the 10th , 25th , 50th , 75th and 90th BMI percentiles over time . Subjects : Participants were enrolled in the National Institute of Child Health and Human Development ( NICHD ) Study of Early Child Care and Youth Development and include both boys and girls ( n=789 ) . Measurements : Objective ly measured BMI ( kg m–2 ) was the outcome variable and objective ly measured sedentary behavior was the main predictor . Adjustment was also made for MVPA , gender , race , maternal education , hours of sleep and healthy eating index . Results : Increases in BMI were observed at all percentiles , with the greatest increase observed at the 90th BMI percentile . Spending more time in sedentary behavior ( h per day ) was associated with additional increases in BMI at the 90th , 75th and 50th BMI percentiles , independent of MVPA and the other covariates ( 90th percentile=0.59 , 95 % confidence interval ( 95 % CI ) : 0.19–0.98 kg m–2 ; 75th percentile=0.48 , 95 % CI : 0.25–0.72 kg m–2 ; and 50th percentile=0.19 , 95 % CI : 0.05–0.33 kg m–2 ) . No associations were observed between sedentary behavior and changes at the 25th and 10th BMI percentiles . Conclusion : Sedentary behavior was associated with greater increases in BMI at the 90th , 75th and 50th BMI percentiles between ages 9 and 15 years , independent of MVPA . Preventing an increase in sedentary behavior from childhood to adolescence may contribute to reducing the number of children classified as obese", "PURPOSE Physical activity ( PA ) declines dramatically during adolescence , and activity levels are consistently lower among children living in low-income communities . Competency in a range of fundamental movement skills ( FMS ) may serve as a protective factor against the decline in PA typically observed during adolescence . The purpose of this study was to evaluate the effect of a 12-month multicomponent PA and FMS intervention on children attending primary schools in low-income communities . METHODS The Supporting Children 's Outcomes using Rewards , Exercise , and Skills intervention was evaluated using a cluster r and omized controlled trial . The sample included 25 classes from eight primary schools located in low-income communities . Participants were 460 children ( 54.1 % girls ) age 8.5 ± 0.6 yr . Primary outcomes were objective ly measured PA ( ActiGraph GT3X and GT3X+ accelerometers ) , FMS competency ( Test of Gross Motor Development 2 , six locomotor and six object control skills ) , and cardiorespiratory fitness ( 20-m multistage fitness test ) assessed at baseline , midprogram ( 6-months ) , and at posttest ( 12 months ) . Linear mixed models , adjusted for sex , age , body mass index z-score , socioeconomic status , ethnicity , and school class as a r and om factor , were used to assess the effect of the intervention . RESULTS At midprogram , there were no significant intervention effects for any of the outcomes . At posttest ( study 's primary time point ) , there were intervention effects for daily moderate-to-vigorous PA ( MVPA ) ( adjusted mean difference , 12.7 min·d of MVPA ; 95 % confidence interval ( CI ) , 5.0 - 20.5 ) , overall FMS competency ( 4.9 units ; 95 % CI , -0.04 to 9.8 ) , and cardiorespiratory fitness ( 5.4 laps ; 95 % CI , 2.3 - 8.6 ) . CONCLUSIONS A school-based multicomponent PA and FMS intervention maintained daily MVPA , improved overall FMS competency , and increased cardiorespiratory fitness among children attending primary schools in low-income communities", "Background Little is known about the concurrent change in physical activity ( PA ) , sedentary behavior ( SB ) and sport participation ( SP ) during adolescence . The main purpose of this prospect i ve and partly objective study was to simultaneously investigate PA , SBs and SP changes between the 1st and 2nd grade s of high school in urban adolescents . Methods In this 1-year follow-up study , the participants were 81 secondary -school students ( 28 boys and 53 girls ) aged 15.5 years at the baseline . PA was assessed with the SenseWear Armb and multi-sensor activity monitor , while SBs were assessed by using School Health Action , Planning and Evaluation System ( SHAPES ) PA question naire . The SHAPES question naire was supplemented with two questions inquiring about SP in organized sports in school and outside of school . Results PA decreased markedly in both genders between the 1st and 2nd grade s of high school . Total energy expenditure ( TEE ) was reduced by 13 kcal/kg/day on average in boys and by 10 kcal/kg/day in girls ( p for both mean daily active energy expenditure ( AEE ) decreased by 7 kcal/kg/day ( p amount of moderate PA declined by 49 min/day in boys and 21 min/day in girls ( p for both vigorous PA was cut by 14 min/day ( p time spent in SBs did not show any change . Conclusion In conclusion , a decline in PA between the 1st and 2nd grade s of high school was marked but was not accompanied with an increase in SBs . Policies aim ed at increasing PA should be targeting the period of entering secondary school to offset the observed drop in PA", "OBJECTIVES This study aim ed to investigate cross-lagged associations of leaping skill and throwing-catching skills with objective ly measured moderate-to-vigorous physical activity ( MVPA ) and sedentary time ( ST ) during school transition from upper primary ( Grade 6 ) to lower secondary school ( Grade 7 ) . DESIGN This study is a one-year prospect i ve follow-up study within Finnish school setting s. Students ' MVPA , ST , leaping skill and throwing-catching skills were measured at Grade 6 and subsequently at Grade 7 . METHODS A sample of 336 students ( 163 girls , 173 boys ; M age=12.0 years , SD=0.4 at Grade 6 participated in the study . Students ' MVPA and ST were measured objective ly by hip-worn accelerometers . Leaping skill was measured by 5-leaps test . Throwing and catching skills were measured by throwing-catching combination test . Cross-lagged structural equation modeling was conducted to evaluate the associations between MVPA , ST , leaping skill , and throwing-catching skills at Grade 6 and Grade 7 . RESULTS Results demonstrated three significant cross-lagged associations among girls : ( 1 ) leaping skill measured at Grade 6 was negatively associated with ST at Grade 7 ; ( 2 ) objective ly measured MVPA at Grade 6 associated positively with leaping skill at Grade 7 ; and ( 3 ) throwing-catching skills measured at Grade 6 associated positively with leaping skill measured at Grade 7 . There were no statistically significant cross-lagged associations between the study variables for the sample of boys . CONCLUSIONS The results of this study indicated that supporting opportunities for girls ' engagement in both MVPA and leaping skill development activities during their primary school education is strongly recommended", "Background Metabolic health in people with obesity is determined by body composition . In this study , we examined the influence of a combined strength exercise and motivational programme –embedded in the school curriculum– on adolescents body composition and daily physical activity . Methods A total of 695 adolescents ( 11 - 15y ) from nine Dutch secondary schools participated in a one year cluster r and omised controlled trial ( RCT ) . In the intervention schools , physical education teachers were instructed to spend 15–30 min of all physical education lessons ( 2 × per week ) on strength exercises . Monthly motivational lessons were given to stimulate students to be more physically active . Control schools followed their usual curriculum . The primary outcome measure was body composition assessed by the deuterium dilution technique . Daily physical activity and sedentary behaviour measured by accelerometry served as a secondary outcome . Results After 1 year , a 1.6 % fat mass difference was found in favour of the intervention group ( p = .007 ) . This reflected a 0.9 kg difference in fat free mass ( intervention > control ; p = .041 ) and 0.7 kg difference in fat mass ( intervention p = .054 ) . Daily physical activity decreased from baseline to posttest in both groups , but less so in the intervention group ( p = .049 ) . After 1 year , a difference of 0.4 % was found for moderate to vigorous physical activities in favour of the intervention group ( p = .046 ) . No differences in sedentary behaviour , or light physical activity were found between groups . Conclusion In 11–15 year olds , the combination of strength exercises plus motivational lessons contributed to an improvement in body composition and a smaller decrease in physical activity level . Trial registration ID(NTR5676 – retrospectively registered 8 February 2016 ; enrolment of first participant : 2 March 2015 )", "OBJECTIVE The aims of our study were to quantify levels and investigate sex-specific changes and trajectories in VPA longitudinally from age 7 to 15 years . DESIGN Longitudinal observational study . METHODS Participants were part of the Gateshead Millennium Study . Measures were taken at age 7 ( n=507 ) , 9 ( n=510 ) , 12 ( n=425 ) and 15 years ( n=310 ) . Vigorous physical activity was quantified objective ly using ActiGraph GT1 M accelerometers over 5 - 7days at the four time-points . Multilevel linear spline r and om-effects model and trajectory analysis to identify sub-groups were performed . RESULTS In boys , average VPA declined across childhood followed by an increase at adolescence , while in girls , average VPA declined across the 8-year study period . In boys , daily VPA decreased from 9 - 12 years ( 1.70minutes/year ) and increased from 12 - 15 years ( 1.99minutes/year ) ( all p daily VPA decreased from 7 - 9 years ( 1.70minutes/year ) ( p VPA trajectories were identified which differed between the sexes . In boys , one group decreased from an initial relatively high level , one group , initially relatively low , increased , whereas the third one was stable over the 8-year period . In girls , all three groups declined from baseline . CONCLUSIONS Marked sex and age-specific trajectories in VPA change were observed . These novel findings should help sports and exercise medicine specialists , as well as policy makers , in their effort to maintain or increase VPA in childhood and adolescence", "IMPORTANCE The diverse developmental patterns of obesogenic behaviors during childhood and adolescence can be better understood by using new analytic approaches to assess the heterogeneity in variation during growth and development and to map the clustering of behavior patterns . OBJECTIVES To identify distinct trajectories of daily time spent in moderate- to vigorous-intensity physical activity ( MVPA ) from ages 5 to 19 years and to examine the associations of MVPA trajectories with sports participation and television viewing trajectories . DESIGN , SETTING , AND PARTICIPANTS Cohort members in the prospect i ve population -based Iowa Bone Development Study participated in MVPA assessment s via accelerometry from September 16 , 1998 , to December 9 , 2013 , at ages 5 , 8 , 11 , 13 , 15 , 17 , and 19 years and completed a question naire every 6 months on sports participation and daily time spent in television viewing . MAIN OUTCOMES AND MEASURES Trajectories of MVPA ( minutes per day ) , participation in organized sports ( yes or no ) , and television viewing time ( hours per day ) . RESULTS Based on the data from 537 participants ( 50.1 % females ; 94.6 % white ) , we identified 4 MVPA trajectories : consistently inactive ( 14.9 % ) , consistently active ( 18.1 % ) , decreasing moderate physical activity ( 52.9 % ) , and substantially decreasing high physical activity ( 14.1 % ) . All participants in the consistently inactive trajectory also followed a trajectory of no participation in sports . The consistently active trajectory was associated with decreasing an already low television viewing trajectory ( P MVPA during childhood and adolescence . Sports participation could be a critical way to avoid the consistently inactive pattern . Most important , we identified a subset of participants who maintained a seemingly healthy level of MVPA from childhood to young adulthood . The developmental pathways of physical activity and television viewing behaviors could be related . Additional studies should examine the determinants and health consequences of these specific MVPA trajectories" ]	41188e0c-06ff-11f0-808a-c43d1ab1c353
AIMS To identify different types of models used in economic evaluations of smoking cessation , analyse the quality of the included models examining their attributes and ascertain their transferability to a new context . METHODS A systematic review of the literature on the economic evaluation of smoking cessation interventions published between 1996 and April 2015 , identified via Medline , EMBASE , National Health Service ( NHS ) Economic Evaluation Data base ( NHS EED ) , Health Technology Assessment ( HTA ) . The checklist-based quality of the included studies and transferability scores was based on the European Network of Health Economic Evaluation Data bases ( EURONHEED ) criteria . Studies that were not in smoking cessation , not original research , not a model-based economic evaluation , that did not consider adult population and not from a high-income country were excluded . FINDINGS Among the 64 economic evaluations included in the review , the state-transition Markov model was the most frequently used method ( n = 30/64 ) , with quality adjusted life years ( QALY ) being the most frequently used outcome measure in a life-time horizon . A small number of the included studies ( 13 of 64 ) were eligible for EURONHEED transferability checklist . The overall transferability scores ranged from 0.50 to 0.97 , with an average score of 0.75 . The average score per section was 0.69 ( range = 0.35 - 0.92 ) . The relative transferability of the studies could not be established due to a limitation present in the EURONHEED method . CONCLUSION All existing economic evaluations in smoking cessation lack in one or more key study attributes necessary to be fully transferable to a new context	[ "STUDY OBJECTIVES To evaluate the cost-effectiveness of an additional 12-week treatment with varenicline for abstainers who had successfully completed an initial 12-week treatment . DESIGN The Benefits of Smoking Cessation on Outcomes simulation model was used to simulate both direct and indirect effects of smoking cessation . All calculations were performed in 2003 Swedish prices . SETTING Sweden in 2003 . PATIENTS OR PARTICIPANTS The modelled cohort consisted of 25 % of adult smokers motivated to quit smoking ( 168,844 males and 208,737 females ) . The age and sex distributions of the cohort reflect that of the Swedish population in 2003 . INTERVENTIONS Smokers who had achieved abstinence for at least 7 days following 12-week open-label treatment with varenicline were r and omized to receive an additional 12-week treatment with either varenicline or placebo . MEASUREMENTS AND RESULTS The incremental costs per quality -adjusted life-year ( QALY ) gained , for abstainers who received an additional 12-week varenicline treatment compared with only 12 weeks , were Euro 7066 for men and Euro 7108 for women , over a 50-year time horizon . ( 1 Euro approximately equal to SEK 9.12 ) . These estimates excluded indirect effects on production and consumption of increased survival . The corresponding incremental costs per QALY including indirect effects were Euro 24,149 and Euro 24,436 , respectively . Sensitivity analysis indicated that the estimated cost-utility ratios are robust , but relatively sensitive to treatment efficiency and intervention costs . CONCLUSIONS An additional 12-week course of varenicline treatment , provided to abstainers after an initial 12-week treatment , produces relatively low incremental cost-utility ratios in the spectrum of life-saving medical treatments", "Background Smoking is the leading cause of preventable death in the US . While one in five individuals smoke , and 70 % of these indicate a desire to quit , bupropion or placebo for smoking cessation and to provide a foundation for the development of a lifetime smoking-cessation model . Methods The DES model simulated the outcome of a single smoking-cessation attempt over 1 year , in accordance with the clinical trial timeframes . Pharmaceutical costs were assessed from the perspective of a healthcare payer . The model r and omly sample d patient profiles from the pooled varenicline clinical trials . All patients were physically and mentally healthy adult smokers who were motivated to quit abruptly . The model allowed for comparisons of up to five distinct treatment approaches for smoking cessation . In the current analyses , three interventions corresponding to the clinical trials were evaluated , which included brief counselling plus varenicline 1.0 mg twice daily ( bid ) or bupropion SR 150 mg bid versus placebo ( i.e. brief counselling only ) . The treatment periods in the clinical trials were 12 weeks ( target quit date : day 8) , with a 40-week non-treatment follow-up , and counselling continuing over the entire 52-week period in all treatment groups . The main outcome modelled was the continuous abstinence rate ( CAR ; defined as complete abstinence from smoking and confirmed by exhaled carbon monoxide ≤10 ppm ) at end of treatment ( weeks 9–12 ) and long-term follow-up ( weeks 9–52 ) , and total time abstinent from smoking over the course of 52 weeks . The model also evaluated costs and cost-effectiveness outcomes . Results For the varenicline , bupropion and placebo cohorts , respectively , the model predicted CARs for weeks 9–12 of 44.3 % , 30.4 % and 18.6 % compared with observed rates of 44.0 % , 29.7 % and 17.7 % ; over weeks 9–52 , predicted CARs in the model compared with observed rates in the pooled clinical studies were 22.9 % , 16.4 % and 9.4 % versus 22.4 % , 15.4 % and 9.3 % , respectively . Total mean abstinence times accrued in the model varenicline , bupropion and placebo groups , respectively , were 3.6 , 2.6 and 1.5 months and total pharmaceutical treatment costs were $ US261 , $ US442 and $ US0 ( year 2008 values ) over the 1-year model period . Using cost per abstinent-month achieved as a measure of cost effectiveness , varenicline dominated bupropion and yielded an incremental cost-effectiveness ratio of $ US124 compared with placebo . Conclusion The model accurately replicated abstinence patterns observed in the clinical trial data using individualized predictions and indicated that varenicline was more effective and may be less costly than bupropion . This simulation incorporated individual predictions of abstinence and relapse , and provides a framework for lifetime modelling that considers multiple quit attempts over time in diverse patient population s using a variety of quit attempt strategies", "The cost-effectiveness of smoking cessation interventions is well documented . However , most studies are based on r and omized controlled trials ( RCTs ) and provide little information on the differences between subgroups . This study assessed the relative cost-effectiveness of smoking cessation interventions offered to various subgroups of smokers , based on real-life data . Regression analyses provided information on the factors determining abstinence and costs and led to the formation of relevant subgroups of smokers . Probabilistic Markov modeling was then used to estimate the relative cost-effectiveness of smoking cessation interventions for the entire data base population and for the subgroups compared to a no-intervention case . The ICER for the base case population was estimated at € 1,358 . This is consistent with results from the existing literature . Group simulations showed lower ICERs for men , hospitals , and light smokers and falling ICERs with increasing age . Despite differences in the cost-effectiveness ratios between subgroups our results do not justify any kind of subgroup differentiation in a smoking prevention policy", "BACKGROUND The aim of this study was to evaluate and compare the cost-effectiveness of varenicline with nicotine replacement therapy ( NRT ) for smoking cessation in four European countries ( Belgium , France , Sweden and the UK ) . METHODS Markov simulations , using the Benefits of Smoking Cessation on Outcomes ( BENESCO ) model , were performed . We simulated the incidence of four smoking-related morbidities : lung cancer , chronic obstructive pulmonary disease , coronary heart disease and stroke . The model computes quality -adjusted life-years gained and incremental cost-effectiveness ratios . Incremental cost-utility ratios were calculated , adopting a lifetime perspective . Efficacy data were obtained from a r and omized open-label trial : Week 52 continuous abstinence rates were 26.1 % for varenicline and 20.3 % for NRT . RESULTS The analyses imply that for countries analysed , smoking cessation using varenicline versus NRT was associated with reduced smoking-related morbidity and mortality . The number of morbidities avoided , per 1000 smokers attempting to quit , ranged from 9.7 in Belgium to 6.5 in the UK . The number of quality -adjusted life-years gained , per 1000 smokers , was 23 ( Belgium ) ; 19.5 ( France ) ; 29.9 ( Sweden ) ; and 23.7 ( UK ) . In all base-case simulations ( except France ) , varenicline dominated ( more effective and cost saving ) NRT regarding costs per quality -adjusted life-year gained ; for France the incremental cost-effectiveness ratio was 2803 . CONCLUSION This cost-effectiveness analysis demonstrated that since varenicline treatment was more effective , the result was increased healthcare cost savings in Belgium , Sweden and the UK . Our results suggest that funding varenicline as a smoking cessation aid is justifiable from a healthcare re source allocation perspective", "Introduction : An employer-based cost-benefit analysis for varenicline versus bupropion was conducted using clinical outcomes from a recently published trial . Methods : A decision tree model was developed based on the net benefit of treatment to produce a nonsmoker at 1 year . Sensitivity analyses were conducted based on quit rates with placebo and varenicline and the cost of varenicline . Results : Estimated 12-month employer cost savings per non-smoking employee were $ 540.60 for varenicline , $ 269.80 for bupropion SR generic , $ 150.80 for bupropion SR br and , and $ 81.80 for placebo . Varenicline was more cost beneficial than placebo , which had quit rates of 16.9 % or less . The quit rate with varenicline would have to be ≤16.9 % to lose cost benefit over bupropion SR generic . Conclusions : The economic benefit of varenicline is improved over bupropion , despite the increased initial cost of varenicline", "Background Physician training in smoking cessation counseling has been shown to be effective as a means to increase quit success . We assessed the cost-effectiveness ratio of a smoking cessation counseling training programme . Its effectiveness was previously demonstrated in a cluster r and omized , control trial performed in two Swiss university out patients clinics , in which residents were r and omized to receive training in smoking interventions or a control educational intervention . Design and methods We used a Markov simulation model for effectiveness analysis . This model incorporates the intervention efficacy , the natural quit rate , and the lifetime probability of relapse after 1-year abstinence . We used previously published results in addition to hospital service and outpatient clinic cost data . The time horizon was 1 year , and we opted for a third-party payer perspective . Results The incremental cost of the intervention amounted to US$ 2.58 per consultation by a smoker , translating into a cost per life-year saved of US$ 25.4 for men and 35.2 for women . One-way sensitivity analyses yielded a range of US$ 4.0 - 107.1 in men and US$ 9.7 - 148.6 in women . Variations in the quit rate of the control intervention , the length of training effectiveness , and the discount rate yielded moderately large effects on the outcome . Variations in the natural cessation rate , the lifetime probability of relapse , the cost of physician training , the counseling time , the cost per hour of physician time , and the cost of the booklets had little effect on the cost-effectiveness ratio . Conclusions Training residents in smoking cessation counseling is a very cost-effective intervention and may be more efficient than currently accepted tobacco control interventions", "Abstract Objectives : To conduct a cost-utility analysis of two 12-week smoking-cessation interventions in Japan : smoking-cessation counselling by a physician compared with use of varenicline , an oral smoking-cessation drug , in addition to counselling . Methods : A Markov model was constructed to analyse lifetimemedical costs and QALYs from the perspective of the healthcare payer . The cycle length was 5 years . Both costs and QALYs were discounted at 3 % annually . The cohort of smokers was classified by sex and age , and we assumed that smokers started smoking at the age of 20 years and received smoking-cessation therapy at the ages of 30 , 40 , 50 , 60 or 70 years ( five separate models were run ) . The healthcare costs and QALYs were calculated throughout the term until the age of 90 years . In the base-case analysis , success rates of varenicline plus counselling and counselling alone were assumed to be 37.9 % and 25.5 % , respectively , in male smokers , and 22.2 % and 16.1 % , respectively , in female smokers , based on a r and omized controlled trial conducted in Japan . Both univariate and probabilistic sensitivity analyses were conducted . Results : Prescribed varenicline was shown to be more effective and less costly than smoking-cessation counselling alone . Varenicline would save direct medical costs of Japanese Yen (¥)43 846 ( $ US381 ; $ US1= ¥ 115 ; Oct 2007 ) and generate an increase of 0.094 QALYs in male smokers . In females the incremental costeffectiveness ratio was ¥ 346 143 per QALY gained . Varenicline is estimated to save ¥ 23.7 billion ( $ US206 million ) of the medical costs for tobacco-associated diseases for the whole population . Overall savings are ¥ 9.5 billion . Sensitivity analyses suggested the robustness of the results . Conclusion : As with any data of this nature , there is some uncertainty in the results and further research is warranted . However , based on the results of this pharmacoeconomic evaluation , varenicline , the first non-nicotine , oral treatment developed for smoking cessation , appears to be cost effective and may contribute to future medical cost savings in Japan", "BACKGROUND The 1998 UK government White Paper Smoking Kills emphasises that normal practice should be for general practitioners ( GPs ) , practice nurses , and others to offer advice and support to smokers in their efforts to stop . However , GPs are not allowed to write NHS prescriptions for nicotine-replacement therapy , even though this is the only effective pharmaceutical treatment available in the UK . We estimated the cost-effectiveness , for the NHS , of allowing GPs to prescribe transdermal nicotine patches for up to 12 weeks . METHODS We used data from a r and omised , placebo-controlled efficacy trial of nicotine patches and a survey of associated re source use in 30 GP surgeries in 15 English counties . We calculated the health benefit of nicotine-patch treatment in number of life years that would be saved by stopping smoking at various ages , and used an abstinence-contingent treatment model to calculate the incremental cost per life year saved by GP counselling with nicotine-patch treatment over GP counselling alone . Cost effectiveness was assessed on the basis that GPs would provide repeat NHS prescriptions for up to 12 weeks if the treatment was proving successful . FINDINGS If GPs were allowed to prescribe transdermal nicotine patches on the NHS , for up to 12 weeks , the incremental cost per life year saved would be : Pound Sterling 398 per person younger than 35 years ; Pound Sterling 345 for those aged 35 - 44 years ; Pound Sterling 432 for those aged 45 - 54 years ; and Pound Sterling 785 for those aged 55 - 65 years . INTERPRETATION The low cost per life year saved would make GP intervention against smoking a cost-effective life-saving treatment . The priniciples of the government White Paper could be cost-effectively extended into general practice to reduce smoking and smoking-related illnesses", "BACKGROUND Smoking cessation can be encouraged by reimbursing the costs of smoking cessation support ( SCS ) . The short-term efficiency of reimbursement has been evaluated previously . However , a thorough estimate of the long-term cost-utility is lacking . OBJECTIVES To evaluate long-term effects of reimbursement of SCS . METHODS Results from a r and omized controlled trial were extrapolated to long-term outcomes in terms of health care costs and ( quality adjusted ) life years ( QALY ) gained , using the Chronic Disease Model . Our first scenario was no reimbursement . In a second scenario , the short-term cessation rates from the trial were extrapolated directly . Sensitivity analyses were based on the trial 's confidence intervals . In the third scenario the additional use of SCS as found in the trial was combined with cessation rates from international meta-analyses . RESULTS Intervention costs per QALY gained compared to the reference scenario were approximately euro1200 extrapolating the trial effects directly , and euro4200 when combining the trial 's use of SCS with the cessation rates from the literature . Taking all health care effects into account , even costs in life years gained , result ed in an estimated incremental cost-utility of euro4500 and euro7400 , respectively . In both scenarios costs per QALY remained below euro16 000 in sensitivity analyses using a life-time horizon . CONCLUSIONS Extrapolating the higher use of SCS due to reimbursement led to more successful quitters and a gain in life years and QALYs . Accounting for overheads , administration costs and the costs of SCS , these health gains could be obtained at relatively low cost , even when including costs in life years gained . Hence , reimbursement of SCS seems to be cost-effective from a health care perspective", "Abstract Background and Objective : Varenicline is a nicotinic acetylcholine receptor partial agonist that is approved for use as an aid to smoking cessation . R and omized clinical trials show that its efficacy is superior to that of other current smoking cessation therapies . This study set out to determine the cost effectiveness of varenicline relative to other smoking cessation interventions ( bupropion and nicotine replacement therapy [ NRT ] ) as well as brief counselling alone and unaided cessation in a cohort of Belgian adult smokers making a one-time quit attempt , from the perspective of the healthcare payer ( public and private ) . Methods : A Markov model , the Benefits of Smoking Cessation on Outcomes ( BENESCO ) model , was applied to calculate the long-term health and economic benefits of smoking cessation . Cost effectiveness was expressed as cost per life-year ( LY ) gained and cost per quality -adjusted life-year ( QALY ) gained . Clinical and economic model inputs were obtained from the literature and public healthcare data bases . Costs were discounted at 3 % and health outcomes at 1.5 % . A probabilistic sensitivity analysis and a one-way sensitivity analysis were performed to test the robustness of the results . Results : Varenicline is associated with a reduction of smoking-related morbidity and mortality as well as with a decrease in healthcare costs compared with the pharmacological agents bupropion and NRT . Varenicline also leads to additional LYs and QALYs compared with brief counselling alone and unaided cessation over a lifetime period . Varenicline is a dominant strategy compared with bupropion and NRT . Compared with brief counselling alone and unaided cessation , varenicline presents a cost/QALY of € 240 and € 1656 , respectively . Conclusion : Varenicline is a cost-effective alternative to brief counselling and unaided cessation , and is a cost-saving treatment in comparison with bupropion and NRT , in a Belgian population of smokers willing to quit", "OBJECTIVE To assess the relative cost-effectiveness of a high-intensity treatment ( HIT ) and a low-intensity treatment ( LIT ) for smoking cessation . METHODS The societal and health care perspective economic evaluation was based on the reported number of quitters at 12-month follow-up ( point prevalence ) from a r and omized controlled trial of 2 smoking cessation programs in Sweden . Future disease-related costs ( in Swedish kronor [ SEK ] 2004 ; SEK7.35 = USD1 ) and health effects ( in quality -adjusted life-years [ QALYs ] ) were estimated via a Markov model comprising lung cancer , chronic obstructive pulmonary disease , and cardiovascular disease including stroke with costs and QALYs discounted 3 % annually . RESULTS HIT was more effective than LIT ( 23 % vs. 16 % quitters ) , but at a considerably higher intervention cost : SEK26,100 versus 9,100 per quitter . The model-estimated societal costs avoided did not balance the higher intervention costs , so the incremental cost-effectiveness ratio ( ICER ) amounted to SEK100,000 per QALY for HIT versus LIT . All sensitivity analyses indicated an ICER below SEK300,000 and that HIT is the preferred option if the decision maker willingness-to-pay exceeds SEK50,000 per QALY . Compared with no intervention , LIT was cost saving , whereas HIT was estimated at SEK8,400 per QALY . CONCLUSIONS Compared with no smoking cessation program , it is a societal waste not to implement the LIT as it is estimated to result in lower societal costs . The incremental cost per QALY gained of SEK100,000 for HIT is considered very cost-effective in Sweden . Thus , if smoking cessation programs are judged in the same manner as other Swedish health care measures , the high-intensity program should be chosen before the low-cost program" ]	41188e48-06ff-11f0-808a-c43d1ab1c353
Background Patient-reported outcome measures ( PROMs ) are intended to reflect outcomes relevant to patients . They are increasingly used for healthcare quality improvement . To produce valid measures , patients should be involved in the development process but it is unclear whether this usually includes people with low literacy skills or learning disabilities . This potential exclusion raises concerns about whether these groups will be able to use these measures and participate in quality improvement practice s. Methods Taking PROMs for chronic obstructive pulmonary disease ( COPD ) as an exemplar condition , our review determined the inclusion of people with low literacy skills and learning disabilities in research developing , validating , and using 12 PROMs for COPD patients . The studies included in our review were based on those identified in two existing systematic review s and our up date of this search . Results People with low literacy skills and /or learning disabilities were excluded from the development of PROMs in two ways : explicitly through the participant eligibility criteria and , more commonly , implicitly through recruitment or administration methods that would require high-level reading and cognitive abilities . None of the studies mentioned efforts to include people with low literacy skills or learning disabilities . Conclusion Our findings suggest that people with low literacy skills or learning disabilities are left out of the development of PROMs . Given that implicit exclusion was most common , research ers and those who administer PROMs may not even be aware of this problem . Without effort to improve inclusion , unequal quality improvement practice s may become embedded in the health system	[ "Background : The evidence of benefit for pulmonary rehabilitation ( PR ) programmes is established . However , the optimal duration of a PR programme is not known . A r and omised controlled trial was undertaken in patients with chronic obstructive pulmonary disease ( COPD ) to assess whether a 4 week PR programme was equivalent to our conventional 7 week PR programme at equivalent time points of 7 weeks and 6 months . Methods : One hundred patients ( 56 men ) with stable COPD of mean ( SD ) age 70 ( 8) years and forced expiratory volume in 1 second ( FEV1 ) 1.13 ( 0.50 ) litres were r and omised to either a 7 week ( n = 50 ) or 4 week ( n = 50 ) supervised PR programme . Patients were assessed at baseline , at completion of the supervised PR programme , and 6 months later . Patients r and omised to the 4 week group were also assessed at the 7 week time point . Outcome measures were the Incremental Shuttle Walk Test , Endurance Shuttle Walk Test ( ESWT ) , Chronic Respiratory Question naire-Self Reported , and the Breathing Problems Question naire . Results : Forty one patients in each group completed the PR programme . Patients made significant within group improvements after supervised rehabilitation . There were no statistically significant differences between the groups for any other measure at the 7 week or 6 month time points , except that patients in the 4 week group attained higher ESWT times ( mean difference 124 seconds ( 95 % CI 17.00 to 232.16 ) , p = 0.024 ) at the 7 week time point . Conclusions : A shortened 4 week supervised PR programme is equivalent to a 7 week supervised PR programme at the comparable time points of 7 weeks and 6 months", "Guidelines for the prescription of long-term oxygen therapy ( LTOT ) in hypoxemic COPD patients are based on two l and mark studies in which survival was the primary outcome . Such patients are importantly symptomatic with poor health-related quality of life ( HRQL ) but the effect of LTOT on HRQL remains uncertain . We undertook a prospect i ve longitudinal interventional study of consecutive COPD patients referred to our regional oxygen service ; n = 43 fulfilling criteria and commenced on LTOT , n = 25 not fulfilling criteria and continued on st and ard care . HRQL was measured at baseline , 2 and 6 months . Both patient groups had severe COPD as defined by mean FEV1 At baseline the LTOT group demonstrated significantly worse HRQL as defined by the Chronic Respiratory Question naire ( CRQ ) ( fatigue , emotional function , mastery and total scores ) , total generic Dartmouth COOP Charts and anxiety domain of the Hospital Anxiety and Depression scale . Significant improvements in HRQL were noted at 2 and 6 months in the LTOT group . Conversely the non-LTOT group demonstrated a progressive decline in HRQL . Using vali date d criteria for a minimal clinical ly significant improvement in CRQ , there were 28 ( 67 % ) and 26 ( 68 % ) ' responders ' at 2 and 6 months respectively in the LTOT group . The introduction of LTOT to patients with severe COPD fulfilling st and ard criteria was associated with early significant improvements in HRQL with sustained or further response at 6 months", "STUDY OBJECTIVE To determine whether currently available measurement tools can be used to obtain valid measurements of short-term changes in dyspnea and disease-specific quality of life ( QOL ) in out patients with an acute COPD exacerbation . DESIGN Prospect i ve cohort study . METHODS Sixty-six patients with an acute COPD exacerbation who presented to the emergency department completed the chronic respiratory disease index question naire ( CRQ ) and the baseline dyspnea index ( BDI ) and were discharged home receiving 10 days of medical therapy . Re assessment with the CRQ and the transitional dyspnea index ( TDI ) occurred within 48 h of relapse ( defined as an urgent hospital revisit within 10 days because of worsening respiratory symptoms ) , or 10 days later if relapse did not occur . RESULTS Patients who did not relapse ( n = 49 ) showed moderate-to-large improvements in disease-specific QOL across all four CRQ domains ( improvements in each domain of 1.4 to 1.9 U ; p TDI ( total TDI score , + 5.02 plus minus 0.55 U ; p = 0.0001 ) . In contrast , patients who had a relapse ( n = 17 ) did not have improved CRQ or TDI scores ( mean negative change in three of four CRQ domains , total TDI score - 3.06 plus minus 1.14 U ; p = 0.02 ) . Changes in the CRQ dyspnea score and TDI correlated with each other ( r = 0.78 ; p = 0.0001 ) and with changes in FEV(1 ) ( CRQ , r = 0.48 and p = 0.0001 ; TDI , r = 0.46 and p = 0.0002 ) . Ten control patients with stable COPD showed no changes in the CRQ or TDI over 10 days . CONCLUSION The CRQ and BDI/TDI can be used to obtain valid , responsive measures of acute changes in QOL and dyspnea associated with a COPD exacerbation . The direction and magnitude of change in these scores was highly correlated with clinical outcome and with other health measures . Most out patients treated for a COPD exacerbation experience significant short-term improvements in QOL and dyspnea , with the exception of patients who have a clinical relapse of symptoms", "Background and Purpose — The purpose of this study was to examine proxy – patient agreement on the domains of the Stroke Impact Scale ( SIS ) , as per the proxy – proxy perspective . Methods — Stroke patients were prospect ively assessed by means of the NIH Stroke Scale , Barthel index , and modified Rankin scale . Proxies and patients answered the Hospital Anxiety and Depression Scale and the SIS 3.0 . Comparisons of patient – proxy mean scores ( paired t test ) , effect size , and intraclass correlation coefficients ( ICC ) were calculated for each of the SIS domains , and weighted kappa for individual items . Results — 180 proxy – patient pairs were assessed . Proxies were younger ( mean age : 43.1 versus 57.9 years ) and had a higher education level ( P ) . The bias between patient – proxy mean differences was low ( from 5.3 , Strength , to 0.1 , Communication ) . Proxies significantly scored patients as more severally affected in Strength ( 41.7 versus 36.6 ; P ADL ( 46.2 versus 43.1 ; P=0.01 ) domains , and Composite Physical Domain ( CPD ; 39.7 versus 34.9 ; P ICC values for the SIS domains ranged from 0.17 ( Emotion ) to 0.79 ( H and function ) . The ICC value for the CPD was 0.83 . Memory , Communication , Emotion , and Social Participation domains had ICC lower values . The weighted kappa values for the SIS items ranged from 0.09 ( item 4e ) to 0.80 ( item 7d ) . Highest values ( moderate/high agreement ) were observed for the SIS-16 and CPD ( kappa values : 0.31 to 0.80 ) . Conclusions — Agreement between stroke patients and proxies was acceptable for most SIS domains and SIS-16 . Proxy ’s assessment of SIS subjective domains should be taken with caution", "Background The COPD ( chronic obstructive pulmonary disease ) assessment test ( CAT ) is a recently introduced , simple to use patient-completed quality of life instrument that contains eight questions covering the impact of symptoms in COPD . It is not known how the CAT score performs in the context of clinical pulmonary rehabilitation ( PR ) programmes or what the minimum clinical ly important difference is . Methods The introduction of the CAT score as an outcome measure was prospect ively studied by PR programmes across London . It was used alongside other measures including the St George 's Respiratory Question naire , the Chronic Respiratory Disease Question naire , the Clinical COPD Question naire , the Hospital Anxiety and Depression score , the Medical Research Council ( MRC ) dyspnoea score and a range of different walking tests . Patients completed a 5-point anchor question used to assess overall response to PR from ‘ I feel much better ’ to ‘ I feel much worse ’ . Results Data were available for 261 patients with COPD participating in seven programmes : mean ( SD ) age 69.0 ( 9.0 ) years , forced expiratory volume in 1 s ( FEV1 ) 51.1 ( 18.7 ) % predicted , MRC score 3.2 ( 1.0 ) . Mean change in CAT score after PR was 2.9 ( 5.6 ) points , improving by 3.8 ( 6.1 ) points in those scoring ‘ much better ’ ( n=162 ) , and by 1.3(4.5 ) in those who felt ‘ a little better ’ ( n=88 ) ( p=0.002 ) . Only eight individuals reported no difference after PR and three reported feeling ‘ a little worse ’ , so comparison with these smaller groups was not possible . Conclusion The CAT score is simple to implement as an outcome measure , it improves in response to PR and can distinguish categories of response", "Background Chronic obstructive pulmonary disease ( COPD ) impairs quality of life and leads to premature mortality . COPD sufferers experience progressive deterioration of lung function and decreased ability to undertake day-to-day activities . Ginseng has been used for thous and s of years in Chinese medicine for respiratory symptoms . Several controlled clinical trials using ginseng for COPD have shown promising clinical effect , however these studies were generally small and with some potential bias , prompting the need for rigorously design ed studies . Aim The objective of this study is to evaluate the therapeutic value and safety profile of a st and ardised root extract of Panax ginseng C.A Meyer ( ginseng ) for symptomatic relief , with a focus on quality of life ( QoL ) improvements in individuals with moderate ( Stage II ) COPD FEV1/FVC Methods This paper describes the design of a r and omised , multi-centre , double-blind , placebo controlled , two-armed parallel clinical trial . Two trial sites in Melbourne Australia will proportionately r and omise a total of 168 participants to receive either ginseng capsule ( 100 mg ) or matching placebo twice daily for 24 weeks . The primary outcomes will be based on three vali date d QoL question naires , St Georges Respiratory Question naire ( SGRQ ) , Short Form Health Survey ( SF-36 ) and the COPD Assessment Test ( CAT ) . Secondary outcomes are based on lung function testing , relief medication usage and exacerbation frequency and severity . Safety endpoints include blood tests and adverse event reporting . Intention-to-treat will be applied to all data analyses . Discussion Findings from this study may lead to new therapeutic development for chronic respiratory diseases , particularly COPD . This protocol may also guide other investigators to develop quality herbal medicine clinical trials in the future . Trial registration Australia and New Zeal and Clinical Trials Register ( ANZCTR ) :", "BACKGROUND Marital adjustment has been associated with morbidity and mortality across various chronic diseases but has been largely ignored among patients with chronic obstructive pulmonary disease ( COPD ) . PURPOSE This study was design ed to evaluate the relationship among marital adjustment , quality of life , psychologic functioning , and functional capacity among married patients with COPD who are participating in a 5-week exercise rehabilitation program and their spouses . SAMPLE A convenience sample of 31 patients with COPD and their partners was included . DESIGN A prospect i ve 1-group pretest-posttest study was conducted . RESULTS Marital adjustment scores indicated that patients and partners were , on average , satisfied with their marriages . Patient marital adjustment was associated with patient psychologic well-being , whereas partner marital adjustment was associated with patient physical functioning . In addition , patient and partner perceptions of marital adjustment predicted change in patient functioning after exercise rehabilitation . Patients who entered the program with poor marital adjustment experienced a greater magnitude of improvement in mental health after rehabilitation than did well-adjusted patients . CONCLUSIONS These findings suggest that marital adjustment is associated with both psychologic well-being and physical functioning among patients with COPD , and that it may predict change among patients with COPD participating in exercise rehabilitation", "OBJECTIVE The purpose of this study was to evaluate the influence of rollator use on health-related quality of life in patients with COPD . DESIGN R and omized controlled trial . METHODS Thirty-one postrehabilitation patients with COPD were r and omized to receive a rollator ( n = 18 ) or usual care ( n = 13 ) for 8 weeks and to record the frequency of rollator use . Outcome measures at baseline , 4 weeks , and 8 weeks included the Chronic Respiratory Question naire ( CRQ ) and the 6-min walk ( 6MW ) . RESULTS During acute testing , subjects consistently walked further when assisted ( baseline 6MW : 292 + /- 67 m vs 263 + /- 67 m ; 8 weeks : 283 + /- 65 m vs 259 + /- 68 m [ + /-SD ] ; p = 0.013 ) . However , provision of a rollator at home was not associated with group differences in the CRQ ( p > 0.08 ) or in the unassisted 6MW ( p = 0.4 ) or the assisted 6MW ( p = 0.5 ) . Eight of 18 subjects assigned to the rollator group used the rollator less than three times per week . Regular users demonstrated a consistent improvement in mastery compared with infrequent users ( 4 weeks : 4.7 + /- 0.6 vs 5.2 + /- 0.8 , respectively ; 8 weeks : 5.3 + /- 0.8 vs 4.7 + /- 0.4 ; p = 0.014 ) . CONCLUSIONS Despite evidence of effectiveness during acute testing , this study did not demonstrate a rollator effect on quality of life or exercise capacity when the rollator was provided at home , for a longer period . Actual use of a rollator may be an important determinant of its effect . Therefore , when prescribing a rollator , health-care professionals should attempt to identify those most likely to use it", "OBJECTIVE To document outcomes of a r and omized trial of the PhoenixCare demonstration program of palliative care and coordinated care/case management for seriously chronically ill individuals who simultaneously received active treatment from managed care organizations ( MCOs ) . DESIGN Patients , continuously enrolled between July 1999 , and March 2001 , were r and omly assigned to the PhoenixCare program or a control group receiving usual MCO care . SETTING Hospice of the Valley , Phoenix , Arizona . PARTICIPANTS Participants were 192 patients with chronic obstructive pulmonary disease ( COPD ) or chronic heart failure ( CHF ) , who had an estimated 2-year life expectancy . INTERVENTION Intensive home-based case management provided by registered nurse casemanagers , in coordination with patients ' existing source of medical care , comprised the intervention . Program foci included disease and symptom management , patient self-management of illness and knowledge of illness-related re sources , preparation for end-of life , physical and mental functioning , and utilization of medical services . OUTCOME MEASURES Outcomes , assessed every 3 months by telephone interview , included measures related to all program foci ; the SF-36 was used to evaluate physical and mental functioning ; emergency department visits exemplified medical service utilization . RESULTS Compared to controls , PhoenixCare patients exhibited significantly better outcomes on self-management of illness , awareness of illness-related re sources , and legal preparation for end of life . They reported lower symptom distress , greater vitality , better physical functioning and higher self-rated health than r and omized controls . Emergency department utilization was equivalent across groups . Patients with COPD showed stronger responsiveness to the intervention . CONCLUSION A novel model of patient care that combined greatly enhanced palliative carefocused case management with ongoing MCO-based treatment was associated with improved functioning of chronically severely ill patients in the last years of life", "STUDY OBJECTIVE Measures of health-related quality of life ( HRQL ) correlate with disease stage in persons with COPD . However , as their predictive capacity for mortality or medical utilization is less well defined , we sought to examine the relationship of a general measure of HRQL and outcomes in persons with obstructive lung disease . DESIGN Prospect i ve cohort study . SETTING Upper Midwest Veterans Integrated Service Network (VISN)-13 . PARTICIPANTS All veterans in VISN-13 ( n = 70,017 ) were surveyed with the Veterans Short Form 36 ( SF-36V ) . Persons with reported asthma or COPD who completed the SF-36V formed the study cohort ( n = 8,354 ) . MEASUREMENTS AND RESULTS For purpose s of analysis , individuals were divided into quartiles of HRQL according to their physical component summary ( PCS ) and mental component summary ( MCS ) , values derived from the SF-36V . Outcomes of mortality , hospitalization , and outpatient visits were recorded for 12 months after the survey . Outpatient utilization was dichotomized into high vs low use , with high use being defined as the upper quartile of visits in the 12 months prior to survey mailing . The study cohort had a mean age of 65 years and was largely male ( 95 % ) , both consistent with a veteran population . After correcting for potential confounding factors through multivariable regression , the PCS was independently predictive of death , hospitalization , and high outpatient utilization . When using the first quartile of PCS as the reference population , those in the fourth quartile of PCS had a hazard ratio for death of 5.47 ( 95 % confidence interval [ CI ] , 3.63 to 8.26 ) . Similarly , the odds ratios for hospitalization , high primary care visits , and high specialty medicine visits in the fourth quartile of PCS were 1.82 ( 95 % CI , 1.51 to 2.19 ) , 1.54 ( 95 % CI , 1.26 to 1.87 ) , and 1.46 ( 95 % CI , 1.21 to 1.78 ) , respectively . The MCS , through multivariable regression , was predictive of death but unassociated with subsequent hospitalization or high outpatient utilization . CONCLUSION HRQL , as assessed by the SF-36V , is an independent predictor of mortality , hospitalization , and outpatient utilization in persons with self-reported obstructive lung disease", "Clinical manifestations of chronic obstructive pulmonary disease ( COPD ) , including airflow limitation , dyspnea , and activity limitation , ultimately lead to impaired health-related quality of life ( HRQoL ) . This 9-month , r and omized , double-blind , multicenter study compared the effect of once-daily tiotropium 18 μg and placebo on HRQoL , spirometric parameters , and exacerbations in 554 patients with moderate-to-severe COPD . HRQoL was assessed using the St. George ’s Respiratory Question naire ( SGRQ ) and the new 8-item Visual Simplified Respiratory Question naire ( VSRQ ) , which is currently being vali date d. The primary efficacy endpoint was the proportion of patients achieving a reduction of at least 4 units in the SGRQ total score at study end ( Month 9 ) . Mean ± SD baseline SGRQ total score was 47.4 ± 18.1 . Significantly more tiotropium-treated patients achieved a reduction of at least 4 units in the SGRQ score vs placebo at study end ( 59.1 % vs 48.2 % , respectively ; p = 0.029 ) . Tiotropium significantly improved spirometric parameters ( forced expiratory volume in 1 second [ FEV1 ] : 0.11 ± 0.02 L vs 0.01 ± 0.02 L ; between-group difference : 0.10 ± 0.03 L , p = 0.0001 ) and reduced exacerbations vs placebo . Maintenance treatment with tiotropium provided significant and clinical ly relevant improvements in HRQoL , as measured by the SGRQ", "STUDY OBJECTIVES Previous studies with short recall periods have suggested that informed administration ( previous responses available ) may improve the responsiveness and validity of health-related quality -of-life ( HRQL ) question naires in comparison to blind administration ( previous responses unavailable ) . Informed administration may , however , have less impact in studies with longer recall periods . The objective of this r and omized trial was to compare the validity and responsiveness of the blind and informed Chronic Respiratory Question naire ( CRQ ) and the St. George 's Respiratory Question naire ( SGRQ ) with a 3-month interval between question naire completion . STUDY DESIGN We r and omized 85 patients to blind or informed administration of the CRQ and SGRQ before and after they underwent a st and ard respiratory rehabilitation program . Patients also completed other HRQL instruments . RESULTS At the follow-up administration , we observed important and statistically significant improvement in all four CRQ domains and three SGRQ domains . The results of blind and informed administration differed little . This was true for both the CRQ and the SGRQ , and for both responsiveness and validity . CONCLUSIONS In contrast to the improved measurement properties after shorter recall periods , the administration of the informed version after > or = 12 weeks may not result in improvements in responsiveness or validity", "There is need for a vali date d short , simple instrument to quantify chronic obstructive pulmonary disease ( COPD ) impact in routine practice to aid health status assessment and communication between patient and physician . Current health-related quality of life question naires provide valid assessment of COPD , but are complex , which limits routine use . The aim of the present study was to develop a short vali date d patient-completed question naire , the COPD Assessment Test ( CAT ) , assessing the impact of COPD on health status . 21 c and i date items identified through qualitative research with COPD patients were used in three prospect i ve international studies ( Europe and the USA , n = 1,503 ) . Psychometric and Rasch analyses identified eight items fitting a unidimensional model to form the CAT . Items were tested for differential functioning between countries . Internal consistency was excellent : Cronbach 's α = 0.88 . Test re-test in stable patients ( n = 53 ) was very good ( intra-class correlation coefficient 0.8 ) . In the sample from the USA , the correlation with the COPD -specific version of the St George ’s Respiratory Question naire was r = 0.80 . The difference between stable ( n = 229 ) and exacerbation patients ( n = 67 ) was five units of the 40-point scale ( 12 % ; p COPD health status with worldwide relevance", "BACKGROUND Retinoids promote alveolar septation in the developing lung and stimulate alveolar repair in some animal models of emphysema . METHODS One hundred forty-eight subjects with moderate-to-severe COPD and a primary component of emphysema , defined by diffusing capacity of the lung for carbon monoxide ( Dlco ) [ 37.1 + /- 12.0 % of predicted ] and CT density mask ( 38.5 + /- 12.8 % of voxels into a r and omized , double-blind , feasibility study at five university hospitals . Participants received all-trans retinoic acid ( ATRA ) at either a low dose ( LD ) [ 1 mg/kg/d ] or high dose ( HD ) [ 2 mg/kg/d ] , 13-cis retinoic acid ( 13-cRA ) [ 1 mg/kg/d ] , or placebo for 6 months followed by a 3-month crossover period . RESULTS No treatment was associated with an overall improvement in pulmonary function , CT density mask score , or health-related quality of life ( QOL ) at the end of 6 months . However , time-dependent changes in Dlco ( initial decrease with delayed recovery ) and St. George Respiratory Question naire ( delayed improvement ) were observed in the HD-ATRA cohort and correlated with plasma drug levels . In addition , 5 of 25 participants in the HD-ATRA group had delayed improvements in their CT scores that also related to ATRA levels . Retinoid-related side effects were common but generally mild . CONCLUSIONS No definitive clinical benefits related to the administration of retinoids were observed in this feasibility study . However , time- and dose-dependent changes in Dlco , CT density mask score , and health-related QOL were observed in subjects treated with ATRA , suggesting the possibility of exposure-related biological activity that warrants further investigation", "Study objectives The aims of this study were to establish whether pulmonary rehabilitation ( PR ) improves domestic function and daily activity levels in COPD and whether individually targeted exercise is more effective than general exercise . Design Prospect i ve r and omized , controlled trial . Setting Outpatient PR program in secondary care . Participants One-hundred eighty patients ( mean [ ±SD ] age , 68.3 ± 8.6 years ; FEV 1 , 0.95 ± 0.4 L ; FEV 1 /FVC ratio , 0.51 ± 0.15 ; 111 male patients ; 69 female patients ) with stable COPD . One hundred twenty-one patients completed the study . Interventions Patients were r and omized to a conventional 7-week general exercise program ( [ GEP ] n=90 ) or an individually targeted exercise program ( [ ITEP ] n=90 ) . Measurement and results Daily activity was measured using ambulatory activity monitors ( Z80 –32k V1 Int ; Gaehwiler Electronics ; Hombrechtikon , Switzerl and ) . These were lightweight devices , which contained a uniaxial accelerometer . Domestic function was assessed by the Canadian Occupational Performance Measure ( COPM ) . Exercise performance was assessed by the incremental shuttle walk test ( ISWT ) and the endurance shuttle walk test and health status by the chronic respiratory question naire – self-reported . Activity monitor counts increased by 29.18 % ( 95 % confidence interval [ CI ] , 3.19 to 55.17 ; p=0.03 ) for the GEP and 40.63 % ( 95 % CI , 7.42 to 73.83 ; p=0.02 ) for the ITEP . Mean COPM performance scores increased by 1.71 ( 95 % CI , 1.37 to 2.05 ; p=0.0001 ) for the GEP and 1.46 ( 95 % CI , 1.05 to 1.87 ; p=0.0001 ) for the ITEP . Mean COPM satisfaction scores increased by 2.27 ( 95 % CI , 1.74 to 2.81 ; p=0.0001 ) for the GEP and 2.04 ( 95 % CI , 1.56 to 2.52 ; p=0.0001 ) for the ITEP . ISWT scores increased by 81.72 m ( range , 63.83 to 99.62 ) for the GEP and by 85.52 m ( range , 67.62 to 103.42 ) for the ITEP . No statistically significant difference was found between the general exercise group and the individually targeted exercise group for any outcome measure . Conclusions Pulmonary rehabilitation improves domestic function and physical activity . This study also demonstrates that general exercise training is as effective as individually targeted training", "STUDY OBJECTIVES Several vali date d instruments are used to measure outcomes , such as exercise performance , dyspnea , and health-related quality of life after pulmonary rehabilitation ( PR ) in patients with COPD . However , no study has simultaneously compared the responsiveness of the most frequently used outcome measurements after PR . We design ed this study to investigate the capacity of several of the most frequently used outcome measurements to detect changes after PR in a population of patients with severe COPD who qualified for lung volume reduction surgery . DESIGN , PATIENTS , AND INTERVENTIONS We evaluated 37 patients with severe COPD ( FEV(1 ) 6 to 8 weeks of outpatient PR . The following frequently used tools were evaluated : the 6-min walk distance ( 6MWD ) ; functional dyspnea with the Medical Research Council ( MRC ) scale ; baseline and transitional dyspnea index ( BDI/TDI ) ; resting and 6MWD visual analog scale ( VAS ) ; quality of life with a generic tool ( the Short Form-36 [ SF-36 ] ) ; and two disease-specific tools , the Chronic Respiratory Disease Question naire ( CRQ ) and the St. George 's Respiratory Question naire ( SGRQ ) . RESULTS After PR , mean + /- SD 6MWD increased in 33 of 37 patients ( 89 % ) , from 285 + /- 97 to 343 + /- 92 m ( p = 0.009 ) . Improvements were seen also in the MRC scale in 23 of 37 patients ( 62 % ; from 2.27 + /- 0.8 to 1.86 + /- 0.6 ; p = 0.01 ) ; in CRQ dyspnea in 25 of 37 patients ( 67 % ; from 3.25 + /- 0.9 to 3.90 + /- 1.4 ; p = 0.02 ) ; in CRQ mastery in 22 of 37 patients ( 60 % ; from 4.37 + /- 1.4 to 5.14 + /- 1.3 ; p = 0.01 ) ; and in BDI/TDI functional in 24 of 37 patients ( 64 % ; from 1.4 + /- 0.8 to 0.7 + /- 1.1 ; p = 0.002 ) . There were smaller improvements in the SGRQ in 18 of 37 patients ( 48 % ) and in the SF-36 in 19 of 37 patients ( 51 % ) , but they were not statistically significant . There were good correlations between the dyspnea components of all the tools . The 6MWD change did not correlate with the changes in the other outcomes . Clinical ly significant changes in the values for those outcome tools were detected in > 50 % of patients for the BDI/TDI , 29 % of patients for the MRC scale , in 37 % of patients for the 6MWD , in 48 % of patients for the VAS at peak exercise , in > 50 % of patients for the CRQ , and in 40 % of patients for the SGRQ . CONCLUSIONS We conclude that the VAS peak exercise , BDI/TDI , and CRQ adequately reflect the beneficial effects of PR . The 6MWD evaluates a unique domain not related to quality of life . Due to their simplicity and sensitivity , VAS at peak exercise , 6MWD , and CRQ may be the best practical tools to evaluate responsiveness to PR", "BACKGROUND The exacerbations of chronic obstructive pulmonary disease tool ( EXACT ) is a condition-specific daily diary recently developed to evaluate the frequency , severity , and duration of chronic obstructive pulmonary disease ( COPD ) exacerbations . A preference-based algorithm for the EXACT would allow utilities to be reported from patients during an exacerbation when EQ-5D data are not available . OBJECTIVE To develop the exacerbations of chronic obstructive pulmonary disease tool-utility ( EXACT-U ) , a condition-specific preference-based measure to report utilities from the EXACT for use in cost-effectiveness studies . METHODS Five items with three to five levels comprise the EXACT-U. Two groups of health states and respondents were constructed to allow for model development ( Development group ) and predictive validity testing ( Validation group ) using independent sample s. Members of the UK general public each valued 11 r and omized health states using time trade-offs ( TTOs ) scaled from full health/dead with 10-year duration s. Regression models estimated from the Development group using individual data , mean data , and panel design s. Models assessed by number of inconsistent coefficients estimated and R(2 ) and tested against observed utilities from the Validation group using mean absolute error ( MAE ) and root mean squared error ( RMSE ) . RESULTS A total of 55 health states , including the best and worst states , were valued in TTO interviews conducted with 400 respondents . Ten models were developed . The final preferred model contained no logical inconsistencies and found MAE = 0.04 and RMSE = 0.05 with a predicted utility range from 0.09 to 0.95 . CONCLUSIONS The EXACT-U is a condition-specific preference-based measure with strong predictive validity to report daily utilities during an exacerbation", "Adding a long-acting beta(2)-agonist ( LABA ) by dry powder inhaler ( DPI ) to tiotropium provides significantly increased and sustained bronchodilation in chronic obstructive pulmonary disease ( COPD ) patients over either product alone . To demonstrate similar benefits with a nebulized LABA , a placebo-controlled trial was conducted to evaluate the efficacy and safety of formoterol fumarate inhalation solution in subjects receiving tiotropium as a maintenance treatment for COPD . After a 7 - 14-day screening period using tiotropium 18 microg once daily , subjects with diagnosed COPD ( > or = 25 % to were r and omized to receive 20 microg formoterol fumarate inhalation solution twice daily for nebulization plus tiotropium ( FFIS/TIO ) or nebulized placebo twice daily plus tiotropium ( PLA/TIO ) for 6 weeks . Efficacy was assessed with spirometry at each visit ( Day 1 , Week 1 , 3 , 6 ) , the transition dyspnea index ( TDI ) , and St. George 's Respiratory Question naire ( SGRQ ) . Baseline characteristics were comparable , including mean FEV(1)% predicted . At Week 6 , FEV(1 ) AUC(0 - 3 ) was 1.52 L for FFIS/TIO-treated subjects vs. 1.34 L for PLA/TIO-treated subjects ( p mean TDI scores in the FFIS/TIO and PLA/TIO groups were 2.30 and 0.16 , respectively ( p=0.0002 ) . SGRQ did not change significantly with 6 weeks treatment , with the exception of FFIS/TIO improvements in symptom score vs. PLA/TIO ( p=0.04 ) . More PLA/TIO- than FFIS/TIO-treated subjects experienced AEs ( 39.7 % vs. 22.9 % ) , COPD exacerbations ( 7.9 % vs. 4.5 % ) , and serious AEs ( 3.2 % vs. 1.5 % ) . Nebulized formoterol fumarate in combination with tiotropium provided statistically and clinical ly significant improvements in bronchodilation and symptom control over tiotropium alone and demonstrated good tolerability", "OBJECTIVE To determine the feasibility of distractive auditory stimuli ( DAS ) used during an upper extremity training ( UET ) program on perceived dyspnea , functional performance , and health-related quality of life . In addition , to determine the appropriate music tempo used during the UET . DESIGN Experimental , r and omized , 3-group design with testing at baseline and 4 weeks . SETTING Outpatient . PATIENTS Thirty patients ( 13 male and 17 female ) with moderate to severe chronic obstructive pulmonary disease ( FEV1 41.27 % + /- 18 % predicted ) . INTERVENTION Moderate DAS group ( n = 10 ) and slow DAS group ( n = 10 ) subjects were instructed to perform UET for up to 15 minutes 3 to 5 times a week using DAS ( walkman , audiocassettes ) . The control group ( n = 10 ) received the same instructions , but no DAS . MEASURES AND RESULTS Primary outcome measures were perceived dyspnea , functional performance using the 6-minute peg and ring board ( 6MRPB ) count and health-related quality of life . In addition , all subjects recorded the time of UET performance using self-report ( daily logs ) . A significant increase was seen in 6MRPB count ( P = .002 ) between groups . Moderate DAS subjects increased 6MPRB count 46 + /- 21 rings and slow DAS subjects increased 46 + /- 20 rings from baseline to 4 weeks whereas control subjects increased only 5 + /- 4 rings . No significant differences were noted for the remaining variables . CONCLUSION Subjects who used DAS ( music ) while performing UET improved functional performance whereas controls failed to continue improvement . The DAS is a feasible adjunct to UET that may have the potential to augment the effectiveness of pulmonary rehabilitation training", "This report concerns the development and validation of two patient-reported outcomes question naires developed to assess chronic obstructive pulmonary disease ( COPD ) patients ’ ability to perform morning activities and to evaluate their morning symptoms . Based on interviews with COPD patients , the Capacity of Daily Living during the Morning ( CDLM ) question naire and the Global Chest Symptoms Question naire ( GCSQ ) were developed , linguistically vali date d and incorporated into two multicentre , r and omised trials involving a total of 1,100 COPD patients ; those trials were registered at Clinical Trials.gov ( NCT00496470 and NCT00542880 ) . Data from these trials were used to determine the reliability , validity and responsiveness of the question naires and to derive estimates of minimal important differences ( MIDs ) . Both question naires displayed good-to-high reliability ( Cronbach ’s & agr ; 0.75–0.93 ) . Analysis of convergent validity showed that CDLM and GCSQ scores correlated significantly ( p with symptoms , health-related quality of life ( HRQoL ) and use of rescue medication . In both trials , CDLM and GCSQ scores discriminated between patients with different levels of HRQoL , as assessed by the St George 's Respiratory Question naire for COPD patients ( SGRQ-C ) , but not with disease severity , as assessed by the Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) criteria . A significant improvement in CDLM and GCSQ scores occurred in response to treatment . Estimations of MID scores , corresponding to an SGRQ-C MID of 4 , were 0.20 for the CDLM question naire and 0.15 for the GCSQ . Both the CDLM question naire and the GCSQ are easy-to-use , reliable , responsive , self-administered question naires that report on patients ' symptoms and ability to perform morning activities ", "Chronic obstructive pulmonary disease ( COPD ) is a major cause of morbidity in old age . It leads to reduced quality of life ( QoL ) , but the factors that contribute to this are less understood . There is no consensus on measurement of QoL in elderly COPD patients . We assessed ( a ) factors predicting QoL in elderly COPD out- patients and ( b ) specificity ( SP ) , sensitivity ( SEN ) , positive and negative predictive values ( PPV and NPV ) and repeatability of two disease-specific QoL instruments , the Chronic Respiratory Disease Question naire ( CRQ ) and the Breathing Problems Question naire ( BPQ ) in elderly people . All subjects also completed an ADL measure [ Nottingham Extended ADL ( NEADL ) ] and a measure of psychological well-being [ Brief Assessment of Depression Cards ( BASDEC ) ] as well as a 6-min walk test . Subjects comprised 96 ( 56 men ) elderly out- patients with irreversible COPD aged 70 - 93 years ( mean 78 ) who were clinical ly stable for > or = 6 weeks . Controls were 55 ( 23 men ) aged 71 - 90 years ( mean 78 ) with normal lung function . All were cognitively intact . Mean FEV1/FVC in COPD subjects was 45.5 ( SE = 1.4)% and for controls was 71.4 ( SE = 1.3)% . Repeatability was good for both BPQ and CRQ with no significant difference . There were no significant differences in specificity and positive predictive values between the two question naires but BPQ performed better than CRQ with regard to sensitivity ( P = 0.02 ) and NPV ( P COPD subjects . For BPQ predictive values were NEADL ( P age ( P 6-min walk distance ( P = 0.001 ) ; body mass index ( P resting oxygen saturation ( P household composition ( living alone or with relatives , P = 0.05 ) . In contrast only the following predicted CRQ : NEADL , BASDEC and resting oxygen saturation . Sixteen per cent of the variance in BPQ was accounted for by NEADL score , 9 % by BASDEC , 4 % by age and 3 % by 6-min walk distance ( total r2 = 0.70 ) . It was concluded that : ( 1 ) BPQ provides more valid assessment than CRQ of QoL in elderly COPD subjects ; ( 2 ) severity of disease in terms of its impact on QoL is not predicted by lung function tests ; ( 3 ) the most important determinants of QoL are ADL score and emotional status", "The optimal method of assessing the effect of treatment on the day-to-day function of patients with chronic airflow limitation is not established . Therefore , we examined the performance of the Six Minute Walk test , a rating of dyspnea following the test and three different question naires measuring dyspnea in daily activities , in a controlled trial of inhaled salbutamol and oral theophylline in 24 patients with primarily fixed chronic airflow limitation . Clinical ly important and statistically significant effects of salbutamol and theophylline on dyspnea during day-to-day activities were detected by each measure , but the Chronic Respiratory Question naire ( CRQ ) appeared more powerful than either the Oxygen Cost Diagram or the Medical Research Council Dyspnea Question naire as modified by the R and Corporation . Changes in the CRQ dyspnea score showed a higher correlation with changes in spirometry , walk test score , dyspnea following the walk test , and global ratings of dyspnea than did the other two measures . Results of the walk test demonstrated statistically significant salbutamol and theophylline effects , but suggested that no added benefit could be obtained with both drugs ; the rating of dyspnea following the walk test , however , was consistent with an additive effect . We conclude that the CRQ is a responsive , valid measure of functional status for clinical trials in chronic lung disease , and that when the six minute walk is used as a measure of outcome , dyspnea following the walk test should be measured", "BACKGROUND We present a summary report evaluating the efficacy of lung volume reduction surgery ( LVRS ) in patients with advanced emphysema in the Canadian setting . METHODS Quality of Life measures assessed the efficacy of adding LVRS to best medical care including rehabilitation in this blinded r and omized multicentered controlled trial with 2 years of follow-up . Health utility and quality -adjusted life years ( QALY ) were outcomes central to our economic assessment . RESULTS None of the 32 patients r and omized to the LVRS arm or 30 patients in the best medical care ( BMC ) arm crossed-over and no patients were lost to follow-up . Overall surgical mortality was 16 % at 2 years while the overall medical mortality was 13 % ( p = 0.914 ) . There were no 30-day postoperative deaths but 2 deaths ( 6 % ) occurred within 90 days of r and omization . Surgery reduced the residual volume measured at 6 months by 23 % ( 5,385 mL to 4,322 mL , p = 0.007 ) . There was an increase in forced expiratory volume in 1 second ( FEV1 ) of 30 % ( 265 mL , p = 0.013 ) from baseline , an improvement in the six minute walk test ( 6MWT ) of 78 meters ( p = 0.045 ) , and an increase in Health Utility Index 3 ( HUI3 ) which peaked at 6 months with a difference of 0.16 ( p = 0.129 ) . There was a gain in QALYs of 0.21 ( p = 0.19 ) in the LVRS-arm over the BMC -arm . The LVRS costs an additional 28,119 Canadian dollars ( CAD ) compared with BMC or 133,900 CAD/QALY gained . CONCLUSIONS The addition of LVRS to best medical care including pulmonary rehabilitation improves pulmonary function , exercise activity , and quality of life in selected patients with advanced emphysema . Cost is high but in keeping with other treatment modalities currently available", "OBJECTIVE To compare the st and ard error of measurement ( SEM ) with established st and ards for clinical ly relevant intra-individual change in an evaluation of health-related quality of life . DESIGN Secondary analysis of data from a r and omized controlled trial . SUBJECTS Six hundred and five out patients with a history of cardiac problems attending the general medicine clinics of a major academic medical center . MEASURES Baseline and follow-up interviews included a modified version of the Chronic Heart Failure Question naire ( CHQ ) and the SF-36 . The SEM values corresponding to established st and ards for minimal clinical ly important differences ( MCIDs ) on the CHQ were determined . Individual change on the SF-36 was explored using the same SEM criterion . RESULTS One-SEM changes in this population corresponded well to the patient-driven MCID st and ards on all CHQ dimensions ( weighted kappas ( 0.87 ; P SEM to evaluate individual patient change should be explored among other health-related quality of life instruments with established st and ards for clinical ly relevant differences . Only then can it be determined whether the one-SEM criterion can be consistently applied as a proxy for clinical ly meaningful change", "STUDY OBJECTIVES Pulmonary rehabilitation is an established treatment in patients with chronic lung disease but is not widely utilized . Most trials have been conducted in single centers . The National Emphysema Treatment Trial ( NETT ) provided an opportunity to evaluate pulmonary rehabilitation in a large cohort of patients who were treated in centers throughout the United States . DESIGN Prospect i ve observational study of cohort prior to r and omization in a multicenter clinical trial . SETTING University-based clinical centers and community-based satellite pulmonary rehabilitation programs . PATIENTS AND INTERVENTION A total of 1,218 patients with severe emphysema underwent pulmonary rehabilitation before and after r and omization to lung volume reduction surgery ( LVRS ) or continued medical management . Rehabilitation was conducted at 17 NETT centers supplemented by 539 satellite centers . MEASUREMENTS AND RESULTS Lung function , exercise tolerance , dyspnea , and quality of life were evaluated at regular intervals . Significant ( p exercise ( cycle ergometry , 3.1 W ; 6-min walk test distance , 76 feet ) , dyspnea ( University of California , San Diego Shortness of Breath Question naire score , -3.2 ; Borg breathlessness score : breathing cycle , -0.8 ; 6-min walk , -0.5 ) and quality of life ( St. George Respiratory Question naire score , -3.5 ; Quality of Well-Being Scale score , + 0.035 ; Medical Outcomes Study 36-item short form score : physical health summary , + 1.3 ; mental health summary , + 2.0 ) . Patients who had not undergone prior rehabilitation improved more than those who had . In multivariate models , only prior rehabilitation status predicted changes after rehabilitation . In 20 % of patients , exercise level changed sufficiently after rehabilitation to alter the NETT subgroup predictive of outcome . Overall , changes after rehabilitation did not predict differential mortality or improvement in exercise ( primary outcomes ) by treatment group . CONCLUSIONS The NETT experience demonstrates the effectiveness of pulmonary rehabilitation in patients with severe emphysema who were treated in a national cross-section of programs . Pulmonary rehabilitation plays an important role in preparing and selecting patients for surgical interventions such as LVRS", "The forced expiratory volume in 1 sec ( FEV1 ) is the most established outcome measure in chronic obstructive pulmonary disease ( COPD ) . However , changes in FEV1 in response to treatment are small in relation to the repeatability of the measurement and there is increasing interest in other measures including markers of lower airway inflammation in induced sputum , assessment of symptoms and health status using visual analogue scores , and question naires . Little is known about the repeatability of these measures or the safety of sputum induction in COPD . We have assessed the safety of sputum induction in 61 subjects with moderate and severe COPD who participated in a placebo-controlled cross-over study The within-subject repeatability of sputum markers of airway inflammation , health status using the chronic respiratory disease question naire ( CRQ ) and symptom visual analogue scores ( VAS ) were estimated from the data obtained from before and after 2 weeks of treatment with placebo . Sputum induction was performed on 122 occasions and was successful result ing in a cytospin adequate to assess a differential cell count in 95 % of inductions . The group mean ( SEM ) FEV1 was 1.09 (0.05)[41.6 (2.9)% predicted ] and the mean ( SEM ) fall in FEV1 after sputum induction was 120 ml ( 6 ) and % fall 10.9 % ( 0.55 % ) . Seven inductions were stopped due to a fall in FEV1 > 20 % and at a further 13 visits the full sputum induction protocol was not completed due to development of symptoms . The reproducibility of measurements , calculated by the intra-class correlation coefficient , was relatively high for all indices measured ( 0.4 - 0.95 ) with the exception ofthe proportion of lymphocytes ( 0.15 ) and epithelial cells ( 0.3 ) . The ICC for symptom scores and the CRQ domains ranged between 0.87 and 0.96 . In conclusion , sputum induction is safe and the cell and fluid phase mediators repeatable in the investigation of airway inflammation in patients with COPD . VAS symptom scores and the CRQ are reproducible outcome measures in COPD", "Nebulized solutions of long-acting bronchodilators provide an alternative to DPI and MDI delivery , particularly for COPD patients unable to use h and -held devices easily or correctly . The long-acting beta2-agonist , formoterol fumarate , is differentiated by its onset of significant bronchodilation within 5 min of administration . In a r and omized , double-blind , double-dummy trial , COPD subjects ( n=351 , mean forced expiratory volume FEV1=1.3 L , 44 % predicted ) received nebulized formoterol fumarate ( Perforomist inhalation solution ; FFIS 20 microg ) or DPI ( Foradil Aerolizer ; FA 12 microg ) , or placebo twice daily for 12 weeks . Efficacy was assessed with 12-h pulmonary function tests , and quality of life was assessed before and after treatment with the St. George 's Respiratory Question naire ( SGRQ ) . At the 12-week endpoint , FFIS significantly increased FEV1 AUC0 - 12h relative to placebo ( p tachyphylaxis was observed as indicated by maintained FEV1 AUC and reduced rescue albuterol use throughout treatment . FFIS also significantly increased peak FEV1 , trough FEV1 , and st and ardized FVC AUC0 - 12h compared with placebo . SGRQ assessment at Week 12 demonstrated significant and clinical ly meaningful improvements in total score ( FFIS vs placebo , -4.9 , p=0.0067 ) , symptom , and impact scores . No significant differences in efficacy were observed between the two active treatments . Drug related AEs in the FFIS arm with a frequency > or = 1 % and exceeding placebo were dry mouth , nausea , and insomnia . Nebulized FFIS provided significant improvement in respiratory status and quality of life in subjects with COPD relative to placebo and was well tolerated . The efficacy and safety profile of FFIS was comparable to FA DPI", "OBJECTIVE To assess the psychometric properties of the short-form chronic respiratory disease question naire ( SF-CRQ ) as a quality -of-life ( QOL ) instrument in chronic obstructive pulmonary disease ( COPD ) exacerbations . STUDY DESIGN AND SETTING In a prospect i ve multicenter cohort study , consecutive emergency department ( ED ) patients with COPD exacerbation were interviewed using the SF-CRQ and other instruments . Baseline information was collected in the ED and from follow-up data 2 weeks later . The results of the SF-CRQ were compared with the results of the other instruments and clinical variables by correlation and factor analyses . RESULTS Of the 301 enrolled patients , 80 % reported improvements across each of the domains of the SF-CRQ over the 2-week post-ED period . Overall median changes for the dyspnea , fatigue , emotional function , and mastery domains were 2 , 1 , 1 , and 1.5 , respectively ( P reliability for the change score of the SF-CRQ was high ( Cronbach 's alpha coefficient , 0.82 ) . Overall minimal clinical ly important difference for improvement in the SF-CRQ was 1.01 ( 95 % confidence interval , 0.72 - 1.31 ) . CONCLUSION SF-CRQ is a valid , reliable , and responsive instrument for the assessment of short-term QOL change in patients with COPD exacerbations", "BACKGROUND / OBJECTIVES The chronic respiratory question naire ( CRQ ) , the St. Georges Respiratory Question naire ( SGRQ ) , and the feeling thermometer ( FT ) evaluate change in health-related quality of life ( HRQL ) in patients with chronic airflow limitation ( CAL ) . Although the interpretability , and in particular the minimal important difference ( MID ) in score changes , is well established for the CRQ , this is not the case for the SGRQ and FT . The objective of our study is to explore the interpretation of the SGRQ and FT . METHODS We analyzed data from 84 patients who completed the CRQ , SGRQ , and FT before beginning pulmonary rehabilitation and 3 months later . We calculated correlations between the four CRQ domains ( dyspnea , fatigue , emotional function , and mastery ) and the three SGRQ domains ( symptoms , activities , and impact ) , the SGRQ total score , and the FT . When Pearson 's correlations were > /=0.5 , we constructed regression equations and used the slope to calculate the change in SGRQ and FT score that corresponded to a change in CRQ score of 0.5 ( the MID ) . Having established MID for SGRQ we than used a similar approach to examine the relation between the SGRQ and FT results . RESULTS Comparison with the CRQ dyspnea domain suggested the MID in SGRQ total score is approximately 3.05 with a 95 % confidence interval ( 95 % CI ) ranging from 0.39 to 5.71 and a change of 5.67 ( 95 % CI 3.43 - 7.92 ) represents a moderate change ( 1.0 on the CRQ dyspnea domain ) . The MID for the FT based on the CRQ fatigue domain was 6.1 ( 95 % CI 1.87 - 10.28 ) . The FT MID based on the SGRQ activities domain , impacts domain , and total score were , respectively , 7.4 ( 95 % CI 3.44 - 11.35 ) , 5.6 ( 95 % CI 1.6 - 9.64 ) , and 5.9 ( 95 % CI 1.97 - 9.78 ) . CONCLUSIONS An MID for the SGRQ approximates the previously suggested estimate of 4 on a scale of 0 to 100 . The MID for the FT in patients with CAL is approximately 5 to 8 units on the 0 to 100 scale . These MID estimates should facilitate interpretation of clinical trials in which outcome measures include the SGRQ or FT", "Since the relationships between pulmonary function , exercise capacity , and functional state or quality of life are generally weak , a self report question naire has been developed to determine the effect of treatment on quality of life in clinical trials . One hundred patients with chronic airflow limitation were asked how their quality of life was affected by their illness , and how important their symptoms and limitations were . The most frequent and important items were used to construct a question naire evaluating four dimensions : dyspnoea , fatigue , emotional function , and the patient 's feeling of control over the disease ( mastery ) . Reproducibility , tested by repeated administration to patients in a stable condition , was excellent : the coefficient of variation was less than 12 % for all four dimensions . Responsiveness ( sensitivity to change ) was tested by administering the question naire to 13 patients before and after optimisation of their drug treatment and to another 28 before and after participation in a respiratory rehabilitation programme . In both cases large , statistically significant improvements in all four dimensions were noted . Changes in question naire score were correlated with changes in spirometric values , exercise capacity , and patients ' and physicians ' global ratings . Thus it has been shown that the question naire is precise , valid , and responsive . It can therefore serve as a useful disease specific measure of quality of life for clinical trials", "Using clinical and cl aims records from the National Emphysema Treatment Trial , we sought to identify factors that accurately predicted COPD exacerbations . This prospect i ve cohort study consisted of subjects with severe emphysema r and omized to medical therapy . Exacerbations were defined as a hospitalization or emergency department visit for COPD . Patient characteristics obtained before r and omization were entered as independent variables in multivariable logistic regression models to estimate the risk of exacerbation . Discrimination was determined using the area under the receiver operator characteristic curve ( AUC ) . Baseline measures included demographics , body mass index , pulmonary function , arterial blood gases , radiology studies , dyspnea ( Shortness of Breath Question naire — SOBQ ) , health-related quality of life ( St. George 's Respiratory Question naire — SGRQ ) , 6-minute walk , exercise capacity , medication use , prior exacerbations and co-morbidity . In 610 participants , 26.6 % had a COPD exacerbation over 1-year follow-up . In a model incorporating spirometry , PaO2 , dyspnea , prior exacerbations and co-morbidity , a 5-point decrement in percent predicted FEV1 ( OR 1.16 , 95 % CI 1.00–1.34 ) and a 5-point worsening in SOBQ ( OR 1.08 , 1.02–1.14 ) independently predicted exacerbations ( AUC for full model 0.68 ) . Combining physiologic variables , dyspnea , prior exacerbations and co-morbidity may be useful in identifying patients at high risk for COPD exacerbations", "PURPOSE To evaluate the differences in the long-term outcomes of dyspnea , exercise performance , health-related quality of life , and health re source utilization following a dyspnea self-management program with 3 different \" doses \" of supervised exercise . PATIENTS AND METHODS In a prospect i ve , r and omized , single-blind , 1-year trial , patients with stable chronic obstructive pulmonary disease ( N = 103 ; age 66 + /- 8 , females 57 ; FEV1 44.8 % + /- 14 % predicted ) were r and omly assigned to either : ( 1 ) Dyspnea self-management program ( DM ) ; ( 2 ) DM plus 4 supervised exercise sessions ( DM-exposure ) ; or ( 3 ) DM plus 24 supervised exercise sessions ( DM-training ) . The dyspnea self-management program included individualized education and demonstration of dyspnea self-management strategies , an individualized home walking prescription , and biweekly nurse telephone calls . Outcomes were measured at baseline and every 2 months for 1 year . RESULTS The DM-training group had significantly greater improvements in dyspnea during incremental treadmill test and in exercise performance on the incremental and endurance treadmill tests at 6 and 12 months compared with the other 2 groups . Dyspnea with activities of daily living and self-reported physical functioning significantly improved for all groups over time . The dose-response relationship between supervised exercise and improvement in dyspnea present at 2 months was not sustained over the year . CONCLUSION Consistent with previous findings from evaluation studies of pulmonary rehabilitation programs , the greater number of supervised exercise training sessions improved laboratory dyspnea and performance more than the other two doses of exercise . In the long term , the improvement in dyspnea with activities of daily living and physical functioning was similar for all 3 groups", "Changes in health-related quality of life ( HRQoL ) were evaluated in patients with chronic obstructive pulmonary disease ( COPD ) following treatment with placebo , salmeterol 50 microg twice a day or 100 microg twice a day by metered-dose inhaler . Patients completed the disease-specific St. George 's Respiratory Question naire ( SGRQ ) and the Medical Outcomes Study Short Form 36 ( SF-36 ) at baseline and after 16 wk of treatment . Data from 283 patients ( 95 patients in the placebo group and 94 in each salmeterol group ) were available for HRQoL analysis . Apart from a small difference in ages , all treatment groups were well matched at baseline in terms of forced expiratory volume in one second ( FEV1 ) and HRQoL scores . Compared with placebo , salmeterol 50 microg twice a day was associated with significant improvements in SGRQ \" Total \" and \" Impacts \" scores which exceeded the threshold for a clinical ly significant change . This was not seen with salmeterol 100 microg twice a day . Changes in SGRQ and SF-36 scores correlated . They also showed a weak but significant relationship with FEV1 . This study has shown that a modest change in lung function may be associated with clinical ly significant gain in health and well-being in COPD patients", "BACKGROUND Improvements in health status following pulmonary rehabilitation ( PR ) diminish with time . Acute exacerbations of COPD ( AE COPD s ) negatively impact adherence after PR and likely accelerate this diminution of benefit . This study was design ed to characterize the pre-AE COPD status of patients with moderate or severe COPD who had completed PR , and then to measure the impact of AE COPD s on health-related quality of life ( HRQL ) and functional exercise capacity . METHODS Sixty subjects who completed PR were enrolled in a 6-month observational study and were followed up until an AE COPD occurred . In the event of an AE COPD , primary outcome measures , the 6-min walk test ( 6MWT ) and the chronic respiratory disease question naire ( CRDQ ) , were repeated 2 weeks after the onset of symptoms . Between-group and repeated- measures analyses were performed . RESULTS The mean ( + /- SD ) age of the 53 subjects ( 49 % female ) completing the study was 68 + /- 9 years . Baseline airflow obstruction was moderate in 35 subjects ( 66 % ) and severe in 18 subjects ( 34 % ) . Thirty-four subjects experienced a moderate or severe AE COPD . The mean distance walked on the baseline 6MWT in those subjects who experienced AE COPD s was 350 + /- 95 m , compared to 416 + /- 95 m walked in those subjects who did not ( difference , 66 m ; p 6MWT distance walked ( difference , 59.3 + /- 80 m ; p CRDQ domains of fatigue ( difference , 1 + /- 1.3 ; p emotion ( difference , 0.6 + /- 0.95 ; p mastery ( difference , 0.5 + /- 1.4 ; p Patients with lower functional exercise capacity are more likely to experience AE COPD s following PR . AE COPD s are associated with significant and clinical ly meaningful reductions in functional exercise capacity and HRQL", "PURPOSE Cancer patients who are deficient in literacy skills are particularly vulnerable to experiencing different outcomes due to disparities in care or barriers to care . Outcomes measurement in low literacy patients may provide new insight into problems previously undetected due to the challenges of completing paper- and -pencil forms . DESCRIPTION OF STUDY A multimedia program was developed to provide a quality of life assessment platform that would be acceptable to patients with varying literacy skills and computer experience . One item at a time is presented on the computer touchscreen , accompanied by a recorded reading of the question . Various colors , fonts and graphic images are used to enhance visibility , and a small picture icon appears near each text element allowing patients to replay the sound as many times as they wish . Evaluation questions are presented to assess patient burden and preferences . RESULTS An ethnically diverse group of 126 cancer patients with a range of literacy skills and computer experience reported that the ' talking touchscreen ' ( TT ) was easy to use , and commented on the usefulness of the multimedia approach . CLINICAL IMPLICATION S The TT is a practical , user-friendly data acquisition method that provides greater opportunities to measure self-reported outcomes in patients with a range of literacy skills", "STUDY OBJECTIVES Whereas pulmonary rehabilitation reduces symptoms and improves the quality of life of patients with COPD and is recommended in management guidelines , few patients have access to rehabilitation services . The purpose of this study was to investigate the effectiveness of increasing access to selected components of pulmonary rehabilitation by providing nurse-assisted home care that was composed of patient education , efforts to improve patient self-management skills , and enhanced follow-up . DESIGN We conducted a 6-month , r and omized , controlled trial . SETTING Primary care clinics associated with an urban academic health system . PATIENTS Patients were > or = 45 years of age with a physician diagnosis of COPD , and had a > or = 20-pack-year smoking history , had experienced at least one respiratory symptom during the past 12 months , and had airflow obstruction ( ie , FEV1/FVC ratio , INTERVENTIONS Four nurses were trained in the use of the Global Initiative for Chronic Obstructive Lung Disease guidelines , and two of the four nurses received additional training in collaborative management . Patients were r and omly assigned to usual care ( UC ) , nurse-assisted medical management ( MM ) , or nurse-assisted collaborative management ( CM ) . MEASUREMENTS The main outcome measures were of generic ( Medical Outcome Study 36-item short form [ SF-36 ] , illness intrusiveness ) and disease-specific ( St. George 's respiratory question naire [ SGRQ ] ) quality of life and self-reported health-care utilization . RESULTS Overall , 151 patients ( UC group , 51 patients ; MM group , 49 patients ; and CM group , 51 patients ) completed the study , their average age was 69 years , and 56.9 % were women . The average change in the SF-36 general health domain for the MM group vs the UC group was 1.1 ( 95 % confidence interval [ CI ] , -7.9 to 11.2 ) , and for the CM group vs the UC group the average change was 2.5 ( 95 % CI , -7.0 to 12.3 ) . The corresponding changes in SGRQ total domain were -2.9 ( 95 % CI , -9.8 to 4.1 ) and -2.6 ( 95 % CI , -9.5 to 4.3 ) . There was no change in the number of self-reported emergency department visits or hospitalizations , but the utilization of these services was infrequent . CONCLUSION The findings of our investigation and those from the published literature suggest that interventions to enhance patient education , self-management skills , and follow-up among patients with COPD do not result in clinical ly meaningful improvements in health status or self-reported health-care utilization . Moreover , future studies of disease management programs for patients with COPD need to evaluate interventions that address associated comorbidities , exercise , and social support", "This study assessed the relative validity of the Medical Outcomes Study Short-Form General Health Survey ( SF-36 and SF-12 ) for Australian women and compared norms for the independently administered and embedded SF- 12 . Two sample s of women in New South Wales were r and omly selected from the Medicare data base ( N = 3600 ) . The sample was stratified into young ( 18 to 22 years ) , middle-aged ( 45 to 49 years ) and older ( 70 to 74 years ) women , and into women living in urban ( 40 percent ) , rural ( 30 percent ) and remote ( 30 percent ) areas . In study 3500 households were selected by r and om digit dial . The method was a mailout survey . SF-36 scale scores were similar to US norms . For the older group , health profiles of the independent and embedded SF- 12 differed . For the SF-36 and independently administered SF- 12 , means differed in all three age groups . The SF-12 physical health scores discriminated between women with poor versus good physical health , and mental health scores discriminated between groups who were or were not psychologically distressed on GHQ-12 . The SF- 36 , relative to the SF-12 , appears to be a more reliable measure for examining changes in health status over time and between groups" ]	41188e8e-06ff-11f0-808a-c43d1ab1c353
Introduction The outcomes of using a ceramic-on-ceramic ( CoC ) vs ceramic-on-polyethylene ( CoP ) bearing surface for primary total hip arthroplasty ( THA ) are much debated . We performed a systematic review and meta- analysis of r and omised controlled trials ( RCTs ) to compare and evaluate the outcomes of these 2 bearing surfaces . Material s and Methods Electronic data bases ( PubMed / Medline , CENTRAL , Embase and Web of Science ) were systematic ally search ed for RCTs investigating the association between bearing surfaces and outcomes following primary THA . Two investigators independently review ed studies for eligibility , assessed the risk of bias , extracted and analysed the data . Results In total , 13 RCTs including a total of 2,488 THAs were identified . The Harris Hip Score appeared to be similar between CoC and CoP THAs . The acetabular liner wear rate was lower in CoC than CoP THA , but the meta- analysis showed that the incidence of component-related noise and overall ceramic fracture in CoC group were 14.73 times and 6.02 times higher than CoP THA , respectively . There were no statistically significant differences in rates of radiolucent line formation ( > 1 mm ) , osteolysis , loosening , revision with follow-up ≥ 5 years , intraoperative femoral fracture , dislocation , deep infection , deep venous thrombosis and leg length discrepancy between CoC and CoP THAs . Conclusions There appears to be no clear evidence favouring the use of either a CoC or CoP bearing surfaces in primary THA , further studies with high- quality and longer term follow-up to provide more evidence on this topic are still required	[ "This prospect i ve r and omized study aims to compare the outcome between an alumina ceramic-on-ceramic ( CC ) articulation with a ceramic on ultra-high-molecular-weight polyethylene articulation ( CP ) . Fifty-six hips in 55 patients with mean age 42.2 ( range , 19 - 56 ) each received uncemented components , a 28-mm alumina head with r and omization of acetabular liner . Mean St Michael 's outcome score for each group with up to 10 years follow-up ( median , 8 years ; range , 1 - 10 ) was 22.8 and 22.9 , respectively ( P = .819 ) . Wear was identified in all but 1 CP replacement , but only 12 of the 23 CC . Mean wear in the CP group was 0.11 mm/y and 0.02 mm/yr in the CC group ( P wear in the polyethylene group , there was no significant difference in midterm outcome between the 2 groups", "Wear and osteolysis continue to be major reasons for revision surgery in THA . Ceramic-on-ceramic bearings eliminate polyethylene wear debris . The newest generation of these bearings incorporate nanosized , yttria-stabilized tetragonal zirconia particles producing an alumina matrix composite . We asked whether this new material would perform as well as a conventional bearing in terms of functional hip scores , radiographic migration and osteolysis , complications and survival . As part of a US FDA investigational device exemption study ( G000075 ) , we conducted an initial prospect i ve safety study of 21 alumina matrix composite femoral heads articulating on alumina liners followed by a prospect i ve , r and omized study with 44 more of these articulations and 45 zirconia femoral heads on polyethylene liners . The minimum followup for all patients was 26 months ( mean , 73 months ; range , 26–108 months ) . Harris hip scores and radiographic findings were similar in the two groups as was survivorship ( trial 95 % versus control 93 % ) . There were three reoperations in the trial group and three in the control group . A fractured head retrieval showed a 33 % monoclinic transformation with an increase in surface roughness from 3 to 5 nm at the main wear zone . While our numbers were insufficient to compare device-related complications , the trial device performed as well as the control device in terms of reoperation , and clinical and radiographic outcome . The alumina matrix composite femoral head on an alumina liner provided high survivorship . Level of Evidence : Level II , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence", "Our aim in this prospect i ve study was to compare the bone mineral density ( BMD ) around cementless acetabular and femoral components which were identical in geometry and had the same alumina modular femoral head , but differed in regard to the material of the acetabular liners ( alumina ceramic or polyethylene ) in 50 patients ( 100 hips ) who had undergone bilateral simultaneous primary total hip replacement . Dual energy X-ray absorptiometry scans of the pelvis and proximal femur were obtained at one week , at one year , and annually thereafter during the five-year period of the study . At the final follow-up , the mean BMD had increased significantly in each group in acetabular zone I of DeLee and Charnley ( 20 % ( 15 % to 26 % ) , p=0.003 ) , but had decreased in acetabular zone II ( 24 % ( 18 % to 36 % ) in the alumina group and 25 % ( 17 % to 31 % ) in the polyethylene group , p=0.001 ) . There was an increase in the mean BMD in zone III of 2 % ( 0.8 % to 3.2 % ) in the alumina group and 1 % ( 0.6 % to 2.2 % ) in the polyethylene group ( p=0.315 ) . There was a decrease in the mean BMD in the calcar region ( femoral zone 7 ) of 15 % ( 8 % to 24 % ) in the alumina group and 14 % ( 6 % to 23 % ) in the polyethylene group ( p mean bone loss in femoral zone 1 of Gruen et al was 2 % ( 1.1 % to 3.1 % ) in the alumina group and 3 % ( 1.3 % to 4.3 % ) in the polyethylene group ( p=0.03 ) , and in femoral zone 6 , the mean bone loss was 15 % ( 9 % to 27 % ) in the alumina group and 14 % ( 11 % to 29 % ) in the polyethylene group compared with baseline values . There was an increase in the mean BMD on the final scans in femoral zones 2 ( p=0.04 ) , 3 ( p=0.04 ) , 4 ( p=0.12 ) and 5 ( p=0.049 ) in both groups . There was thus no significant difference in the bone remodelling of the acetabulum and femur five years after total hip replacement in those two groups where the only difference was in the acetabular liner", "The present study was performed to test the hypothesis that different bearing material s have an impact on femoral bone remodelling within the first year after a total hip arthroplasty . A total of 225 patients with osteoarthrosis of the hip or avascular necrosis of the femoral head were included in this r and omised prospect i ve study . All patients had an identical hybrid total hip arthroplasty ( cemented BiMetric stem and cementless RingLoc acetabular cup ) except for the bearing material s : polyethylene-on-zirconia ( n = 78 ) , CoCr-on-CoCr ( n = 71 ) , or alumina-on-alumina ( n = 76 ) . Bone mineral density ( BMD ) was measured with Dual-energy X-ray absorptiometry ( DEXA ) in seven Gruen zones adjacent to the femoral implant . The DEXA scan was performed within one week after surgery and was repeated one year postoperatively . There was no significant difference in periprosthetic BMD change between the three groups . After twelve months the relative BMD decrease was highest in the proximal part of the femur , - 6.2 % in the greater trochanter region and - 12.7 % in the lesser trochanter region . In the distal zones the relative BMD decrease was -5.3 , -4.2 , -2.1 , -2.3 , and -5.6 % , respectively . The use of different bearing material s had no significant impact on femoral bone remodelling adjacent to the cemented hip stem within one year after surgery", "The results of a prospect i ve multicenter trial comparing 357 hips r and omized to total hip arthroplasty with either ceramic-ceramic or ceramic-polyethylene couplings are presented . No statistically significant difference in clinical outcomes scores between the ceramic-ceramic and ceramic-polyethylene groups was observed at any time interval . The mean linear rate was statistically lower ( P ceramic-ceramic group ( 30.5 μm/year ) when compared with the ceramic-polyethylene group ( 218.2 μm/year ) . The rates of ceramic implant fracture ( 2.6 % ) and audible component-related noise ( 3.1 % ) were statistically higher in the ceramic-ceramic group when compared with the ceramic-polyethylene group ( P in the dislocation or revision rate between the groups at the time of last clinical follow-up", "Purpose Very few studies have compared alumina-on-alumina ceramic and alumina-on-highly cross-linked polyethylene bearings in the same patient . The purpose of this prospect i ve r and omised study was to compare the clinical and radiographic results and the prevalence of osteolysis in cementless total hip arthroplasty using an alumina-on-alumina and alumina-on-highly cross-linked polyethylene bearings in young active patients . Methods We prospect ively compared the results of 100 patients ( 200 hips ) who had undergone a cementless total hip arthroplasty with an alumina-on-alumina ceramic bearing in one hip and an alumina-on-highly cross-linked polyethylene in the other . There were 66 men and 34 women with a mean age of 45.3 years ( range , 21–49 years ) at the time of surgery . The mean follow-up was 12.4 years ( range , 11–13 years ) . The patients were assessed clinical ly and radiographically at three months , one year , and annually thereafter . Results Harris hip , Western Ontario and McMaster Universities Osteoarthritis Index , and University of California , Los Angeles activity scores did not show statistically significant differences between the two groups of bearings preoperatively or at the time of final follow-up . Radiographic findings of the component were not significantly different between the two groups . The mean polyethylene linear penetration was 0.031 ± 0.004 mm per year . No hips in either group displayed osteolysis . The Kaplan-Meier survivorship with revision as the end point at 12.4 years was 100 % ( 95 % confidence interval [ CI ] , 94–100 % ) for the femoral component in both groups and 99 % ( 95 % CI , 93–100 % ) for the acetabular component . Conclusion The clinical and radiographic results of using an alumina-on-alumina ceramic and alumina-on-highly cross-linked polyethylene bearings were similar", "Ceramic-on-ceramic coupling is thought to be a durable alternative to metal- or alumina-on-polyethylene pairing . No evidence exists suggesting superior clinical and radiological results for hydroxyapatite-coated stems versus uncoated stems . The aim of this study is to report the performance of an alumina-on-alumina bearing cementless total hip arthroplasty and to compare stems with a tapered design with and without hydroxyapatite coating . We prospect ively analysed the results of cementless tapered femoral stems ( 40 hydroxyapatite-coated versus 22 uncoated stems ) , a metal-backed fibre mesh hydroxyapatite-coated socket and alumina-on-alumina pairing . Of 75 hips studied , 62 were available for follow-up ( mean of 10.5 years after surgery ) . The average Harris hip score was 90 . Only one hydroxyapatite-coated stem was revised for aseptic loosening . One instance of non-progressive osteolysis was detected around a screw of a cup . All other components showed radiographic signs of stable ingrowth . Hydroxyapatite coating of the stem had no significant impact on the clinical or radiological results . Total hip arthroplasty with the presented implant and pairing provides a durable st and ard for all patients requiring hip joint replacement against which all newer generations of cementless implants should be judged", "The higher failure rate of total hip arthroplasty ( THA ) in young , active patients remains a challenge for surgeons . Recently , larger-diameter femoral heads combined with an alumina matrix composite ceramic ( BIOLOX Delta ; CeramTec AG , Plochingen , Germany ) articulation was developed to improve implant longevity and meet patients ' activity dem and s while reducing the risk of component-related complications . The purpose of this study was to determine whether this new device may provide advantages for young , active patients . A prospect i ve , r and omized , controlled trial was conducted on 93 patients ( 113 THAs ) with more than 3 years of follow-up . Patients were r and omly divided into a study group ( 51 THAs ) with a 36-mm Delta ceramic-on-ceramic ( COC ) articulation and a control group ( 62 THAs ) with a common-sized alumina ceramic head on polyethylene liner ( COP ) articulation . Clinical and radiographic results were collected to compare the outcomes and complications , including implant-related failures , osteolysis , and noises . The large-diameter Delta COC articulation provided greater range of motion improvement ( 6.1 ° more ) , similar Harris Hip Scores , and similar complication rates compared with the alumina COP articulation . This study suggests that in the short term , the large-diameter Delta COC articulation results in better range of motion with no higher complication rates ; however , mid-term ( 8 - 10 years ) or longer follow-up is necessary to determine its superiority in young , active patients", "This study determined how ceramic-on-ceramic bearing THA affected joint-specific pain , function and stiffness in the first five postoperative years compared with ceramic-on-highly-crosslinked-polyethylene bearing THA . Subjects less than 61 years of age were r and omized to ceramic-on-ceramic ( CERAMIC ) [ n = 48 ] or ceramic-on-highly-crosslinked-polyethylene ( POLYETHYLENE ) [ n = 44 ] bearing THA . Subjects were assessed using the Western Ontario McMaster Osteoarthritis Index ( WOMAC ) and the R AND 12-Item Health Survey ( R AND -12 ) preoperatively , and at one and five years postoperatively . 92 subjects(50 ( 54 % ) males ; average age = 52 ( SD 6.6 ) years ) were enrolled . 78 ( 85 % ) subjects returned five years postoperatively . All subjects reported improvements at one and five years in all measured indices with no group differences detected . Seven ( 8 % ) subjects experienced postoperative THA complications , none related to bearing surfaces ; two subjects ( POLYETHYLENE ) required revision for instability . Both bearing surfaces provided excellent short-term results in younger subjects", "BACKGROUND Early reports on modern ceramic-on-ceramic total hip replacements have demonstrated excellent clinical and radiographic results with few cases of catastrophic failure , which , in the case of earlier design s , often had been caused by implant fracture . Several reports , however , have noted the presence of audible squeaking . The purpose of the present study was to determine the incidence of squeaking in association with the use of this bearing couple . METHODS During the period from March 2003 to May 2005 , three surgeons performed 159 total hip arthroplasties in 143 patients with use of a ceramic-on-ceramic bearing . One hundred and forty-nine hips ( 131 patients ) were available for review after at least one year of follow-up . These patients were followed prospect ively with use of the modified Hospital for Special Surgery hip score and a patient-administered question naire . Additionally , a control group of sixty hips ( forty-eight patients ) with a metal-on-polyethylene bearing was matched to the ceramic group on the basis of age , sex , and body mass index to compare the incidence of squeaking and other noises . Radiographic evaluations were performed according to previously established criteria . RESULTS Fourteen ( 10.7 % ) of 131 patients described an audible squeak during normal activities . However , squeaking was reproducible clinical ly in only four patients , and only one patient complained of squeaking before being presented with the question naire . The average Hospital for Special Surgery score improved from 19.8 preoperatively to 38.4 at the time of the latest follow-up , indicating excellent clinical results . Ninety-five percent of the patients had a satisfaction score of > or = 8 of 10 . Three hips dislocated . One of those three hips squeaked and was revised because of recurrent dislocations . One patient was considering revision because of squeaking . In the matched metal-on-polyethylene cohort , there were no cases of squeaking . CONCLUSIONS The squeaking hip is a phenomenon that is unique to total hip replacements with hard-on-hard bearings . The incidence of squeaking in association with ceramic-on-ceramic bearings may be higher than previously reported as squeaking are yet to be determined . The use of hard-on-hard bearings offers many advantages in terms of wear reduction , especially for young and active patients . Nonetheless , patients considering ceramic-on-ceramic bearings should be counseled with regard to this phenomenon", "Cross-linked liners were introduced with the promise that they would substantially reduce polyethylene wear . In 1999 , our institution initiated a prospect i ve study to compare the outcome of total hip arthroplasty patients who were r and omized to non-cross-linked Enduron liners with that of total hip arthroplasty patients who were r and omized to Marathon polyethylene liners that had been cross-linked with 5 Mrad ( 50 kGy ) of gamma-irradiation and heat-treated to eliminate free radicals . At a mean follow-up of 5.7 years , the clinical outcomes among the Marathon and Enduron liners were similar . However , the mean wear rate was 0.01 + /- 0.07 mm/y for the Marathon group , which represents a 95 % reduction compared with the mean wear rate of 0.19 + /- 0.12 mm/y for the Enduron group . In addition , the incidence of osteolysis was lower in the Marathon group", "Although the published studies on the outcomes of total hip arthroplasty ( THA ) performed with currently available ceramic components show high survivorship and low bearing wear at midterm followup , concern over ceramic fracture and squeaking persist . For these reasons , the use of ceramic is limited . Recently , a new alumina matrix composite material ( Delta ceramic ) with improved material properties was developed to address these concerns . We report the early outcomes and complications of a prospect i ve , r and omized , multicenter trial of 263 patients ( 264 hips ) at eight centers , comparing a Delta ceramic-on-ceramic ( COC ) articulation with a Delta ceramic head-crosslinked polyethylene bearing combination ( COP ) . There were 177 COC hips and 87 COP hips . Complications were reported for all patients , whereas clinical and radiographic results were provided for the 233 patients with minimum 2-year followup ( average , 31.2 months ; range , 21–49 months ) . The Harris hip scores and clinical , radiographic , and survivorship outcomes were similar in both groups . There were four ( 2 % ) revisions in the COC group and two ( 2 % ) in the COP group . We encountered three intraoperative ceramic liner-related events . In addition , one patient receiving the COC underwent revision for chipping of the ceramic liner , and a second had ceramic fragmentation on followup radiographs but has not undergone revision . These liner related complications remain a concern . No patient reported squeaking in either group ; this leaves us hopeful the new material will lessen the frequency of squeaking . In the short term , the Delta COC articulation provided similar functional scores and survivorship and complication rates with the ceramic head mated with crosslinked polyethylene . Level of Evidence : Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence", "Abstract Ceramic-on-ceramic bearings in THA are a popular alternative to overcome wear concerns in traditional metal-polyethylene bearings . However , squeaking is a potentially worrisome phenomenon in ceramic-on-ceramic THAs which we observed in some of our patients . We review ed all 42 patients who underwent 43 ceramic-on-ceramic noncemented THAs during the time of the study . Squeaking , defined as a reproducible sound of squeaking , clicking , or grating , occurred in nine of 43 implants ( 20.9 % ) . St and ard radiographs were normal . We used CT imaging to determine cup anteversion and inclination angles , comparing the squeaking hips with those of a r and omly selected control group , but found no differences . We then hypothesized specific design features ( stem size , cup size , head size , and neck length of the head ) would be risk factors for squeaking . We found a difference in neck length between squeaking and nonsqueaking implants . A neck length of −4 mm or shorter result ed in a relative risk of 5.56 ( 95 % confidence interval , 1.14–27.01 ) for squeaking . We found a high incidence of squeaking in our population , and we believe this phenomenon is an underreported side effect of these types of bearings . A short neck length of the femoral implant was a risk factor for squeaking in ceramic-on-ceramic THA . Level of Evidence : Level III , therapeutic study", "BACKGROUND Alternative bearings have been explored in an attempt to improve the longevity of total hip prostheses . A Food and Drug Administration ( FDA ) -approved clinical study of a nonmodular acetabular component consisting of a porous metal shell , compression-molded polyethylene , and a ceramic liner inlay was discontinued following reports of early failures . METHODS Between October 1999 and January 2003 , 429 patients were enrolled in a prospect i ve study to evaluate a cementless ceramic-on-ceramic total hip arthroplasty design ( Hedrocel ceramic bearing cup ; Implex , Allendale , New Jersey ) . Two hundred and eighty-two patients ( 315 hips ) were treated with the experimental acetabular implant and 147 patients ( 157 hips ) were treated with an acetabular implant that consisted of the same porous shell but an allpolyethylene liner . Clinical data including a Harris hip score and responses to the Short Form-12 ( SF-12 ) health survey were collected preoperatively and at twelve and twenty-four months postoperatively . Serial radiographs were made preoperatively ; at six weeks , three months , six months , and twelve months postoperatively ; and annually thereafter . Retrieval analysis was performed on all failed explanted components . Failure was defined as fracture or displacement of the ceramic liner out of the acetabular component . In addition , biomechanical testing was performed on unimplanted acetabular components and mechanically altered cups in an effort to recreate the mechanisms of failure . Finite element analysis was used to estimate stress and strain within the ceramic liner under extreme physiologic loading conditions . RESULTS The ceramic liner failed in fourteen of the 315 experimental acetabular components ; all of the failures were at the ceramic-polyethylene interface . Patients with a body weight of > 91 kg had a 4.76 times greater odds of the ceramic liner failing than those who weighed or = 91 kg . Retrieval analysis demonstrated stripe and rim wear with evidence of adhesive wear , indicating a potentially high-friction interaction at the articulation . Finite element analysis demonstrated that the forces on the ceramic liner in cups subjected to extreme loading conditions were insufficient to cause fracture . Biomechanical testing was unable to reproduce an initial ceramic liner displacement in vitro ; however , when the ceramic liner was forcibly displaced prior to biomechanical testing , complete displacement and eventual fracture of the ceramic liner result ed . CONCLUSIONS We hypothesized that the combination of a high patient body weight , an extensive range of motion , and subluxation of the femoral head led to high friction at the articulation between the femoral head and the rim of the liner , which initiated displacement of the ceramic liner . Subsequent normal gait led to further displacement of the liner in all of the fourteen failed components and eventually to ceramic fracture in twelve of the fourteen components" ]	41188eca-06ff-11f0-808a-c43d1ab1c353
Glycemic variability ( GV ) has been an emerging target for preventing complications related to type 2 diabetes . For reducing GV , DPP-IV inhibitors have shown effectiveness compared to other oral anti-hyperglycemic drugs ( OADs ) , but systematic evaluation has yet to be existed . A systematic review and meta- analysis of r and omized controlled trials ( RCTs ) were performed to evaluate the effect of DPP-IV inhibitors compared with other OADs , on GV as measured by mean amplitude of glycemic excursions ( MAGE ) . Search es were conducted using Pubmed , EMBASE , and the Cochrane Library , from which eligible studies were retrieved ; seven RCTs were included in the analysis . DPP-IV inhibitors were found to significantly reduce MAGE compared to other OADs ( mean difference = −14.61 ; 95 % CI = −19.00 to −10.21 ; p sulfonylureas ( mean difference = −14.93 ; 95 % CI = −21.60 to −8.26 ; p with DPP-IV inhibitors more effectively reduced MAGE than stepwise add-on therapies ( p = 0.006 ) , although no differences in MAGE were found based on HbA1c values . These findings indicate that DPP-IV inhibitors are promising alternatives for reducing GV in type 2 diabetes patients . However , further studies utilizing larger numbers of patients and longer-term follow-ups are needed	[ "Abstract Aims / Introduction Dipeptidyl peptidase‐4 inhibitors might have pleiotropic protective effects on cardiovascular disease ( CVD ) , in contrast to sulfonylureas . Therefore , we compared various CVD risk factors between vildagliptin and glimepiride . Material s and Methods We carried out a r and omized , prospect i ve and crossover trial . A total of 16 patients with type 2 diabetes whose glycated hemoglobin was > 7 % were r and omized to add vildagliptin or glimepiride . After 12‐week treatment , each drug was replaced with the other for another 12 weeks . Before and after each treatment , glucose homeostasis and CVD risk factors were assessed , and the continuous glucose monitoring system was applied to calculate glycemic variability . Results The mean age of the participants was 60 years , 31 % were men , body mass index 25.5 kg/m2 and HbA1c 8.41 % . Both vildagliptin and glimepiride significantly decreased glycated hemoglobin and glycemic variability indices . Despite the improved glucose homeostasis , favorable change of CVD markers was not prominent in both the arms , along with significant weight gain . Only plasma stromal cell‐derived factor (SDF)‐1α decreased by 30 % in the vildagliptin arm . According to regression analyses , the reduction of SDF‐1α was independently associated with vildagliptin usage and serum interleukin‐6 changes , but white blood cells were not related with the SDF‐1α changes . Conclusion Compared with glimepiride , vildagliptin arrestingly decreased plasma SDF‐1α , and its clinical implication s should be further investigated", "Background Glycemic variability is associated with the development of diabetic complications through the activation of oxidative stress . This study aim ed to evaluate the effects of a dipeptidyl peptidase 4 inhibitor , vildagliptin , or a thiazolidinedione , pioglitazone , on glycemic variability and oxidative stress in patients with type 2 diabetes . Methods In this open label , r and omised , active-controlled , pilot trial , individuals who were inadequately controlled with metformin monotherapy were assigned to either vildagliptin ( 50 mg twice daily , n=17 ) or pioglitazone ( 15 mg once daily , n=14 ) treatment groups for 16 weeks . Glycemic variability was assessed by calculating the mean amplitude of glycemic excursions ( MAGE ) , which was obtained from continuous glucose monitoring . Urinary 8-iso prostagl and in F2α , serum oxidised low density lipoprotein , and high-sensitivity C-reactive protein were used as markers of oxidative stress or inflammation . Results Both vildagliptin and pioglitazone significantly reduced glycated hemoglobin and mean plasma glucose levels during the 16-week treatment . Vildagliptin also significantly reduced the MAGE ( from 93.8±38.0 to 70.8±19.2 mg/dL , P=0.046 ) , and mean st and ard deviation of 24 hours glucose ( from 38±17.3 to 27.7±6.9 , P=0.026 ) ; however , pioglitazone did not , although the magnitude of decline was similar in both groups . Markers of oxidative stress or inflammation including urinary 8-iso prostagl and in F2α did not change after treatment in both groups . Conclusion In this 16-week treatment trial , vildagliptin , but not pioglitazone , reduced glycemic variability in individuals with type 2 diabetes who was inadequately controlled with metformin monotherapy , although a reduction of oxidative stress markers was not observed", "The aim of this study was to evaluate the effect of gemigliptin vs sitagliptin or glimepiride as initial combination therapy with metformin on glycaemic variability and to assess the correlation between glycaemic variability reduction and the dipeptidyl peptidase‐4 ( DPP‐4 ) inhibition in patients with type 2 diabetes . This multicentre , r and omized , active‐controlled , open‐label exploratory study included 69 patients with HbA1c > 7.5 % . Subjects were r and omized to receive gemigliptin 50 mg ( n = 24 ) , sitagliptin 100 mg ( n = 23 ) or glimepiride 2 mg ( n = 22 ) for 12 weeks . After 12 weeks , the change in mean amplitude of glycaemic excursion ( MAGE ) compared with baseline was significantly lower in the DPP‐4 inhibitor groups compared with that in patients who received glimepiride . Furthermore , the st and ard deviation ( SD ) of glucose was significantly lower in patients who received gemigliptin than that in patients who received sitagliptin or glimepiride . The DPP‐4 inhibition was significantly correlated with changes in MAGE and SD of glucose . In conclusion , gemigliptin and sitagliptin were more effective than glimepiride in reducing glycaemic variability as initial combination therapy with metformin in patients with type 2 diabetes , and the DPP‐4 inhibition was associated with a reduction in glycaemic variability ", "OBJECTIVE HbA(1c ) is a st and ard clinical assessment of glycemia and the basis of most data relating glycemic control to complications . It remains unclear , however , whether HbA(1c ) is affected by glycemic variation and mean glycemia . RESEARCH DESIGN AND METHODS To test this question , we analyzed the statistical relationship between HbA(1c ) levels and glycemic variability as measured by self-monitoring of blood glucose ( SMBG ) . The records of 256 subjects were studied . SMBG data for the preceding 3 months were downloaded , and HbA(1c ) was measured by ion-exchange high-performance liquid chromatography . Simple- and r and om-effects linear regression models were used to assess the independent contributions of mean blood glucose ( BG ) and SD of BG to HbA(1c ) , after adjusting for the mean BG . RESULTS Mean + /- SD for HbA(1c ) was 7.66 + /- 1.11 % and for BG was 8.5 + /- 1.9 mmol/l ( 153.3 + /- 34.9 mg/dl ) ; SD of BG for individual subjects was 3.5 mmol/l ( 63.3 mg/dl ) , varying from 0.4 mmol/l ( 8.1 mg/dl ; very stable glycemia ) to 8.4 mmol/l ( 152.5 mg/dl ; very unstable glycemia ) . A close correlation between mean BG and HbA(1c ) was demonstrated ( r = 0.62 ) . Also , within-subject SD of BG correlated with HbA(1c ) ( r = 0.375 ) , indicating that people with poorer glycemic control had higher BG variance . After adjusting for mean BG in a linear regression model , however , the effect of the within-subject SD of BG on the HbA(1c ) was insignificant . Several further analyses confirmed the strength of the observation . CONCLUSIONS HbA(1c ) reflects mean glycemia and is not meaningfully affected by glycemic instability after adjusting for mean BG", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "Aims Type 2 diabetes is associated with endothelial dysfunction leading to cardiovascular disease . CD34 + endothelial Progenitor Cells ( EPCs ) are responsible for endothelial repair and neo-angiogenesis and can be used as a cardiovascular disease risk biomarker . This study investigated whether the addition of saxagliptin , a DPP-IV inhibitor , to metformin , may reduce cardiovascular disease risk in addition to improving glycemic control in Type 2 diabetes patients . Methods In 12 week , double-blind , r and omized placebo-controlled trial , 42 subjects already taking metformin 1–2 grams/day were r and omized to placebo or saxagliptin 5 mg . Subjects aged 40–70 years with diabetes for We evaluated EPCs number , function , surface markers and gene expression , in addition to arterial stiffness , blood biochemistries , resting energy expenditure , and body composition parameters . A mixed model regression to examine saxagliptin vs placebo , accounting for within-subject autocorrelation , was done with SAS ( p increase in CD34 + cell number , CD31 + cells percentage increased . Saxagliptin increased migration ( in response to SDF1α ) with a trend of higher colony formation count . MNCs cytometry showed higher percentage of CXCR4 double positivity for both CD34 and CD31 positive cells , indicating a functional improvement . Gene expression analysis showed an upregulation in CD34 + cells for antioxidant SOD1 ( p downregulation in CD34− cells for IL-6 ( p For arterial stiffness , both augmentation index and systolic blood pressure measures went down in saxagliptin subjects ( p 0.05 ) . ConclusionS axagliptin , in combination with metformin , can help improve endothelial dysfunction in early diabetes before macrovascular complications appear . Trial registration Trial is registered under clinical trials.gov ,", "The objective of this study was to investigate the characteristics of blood glycemic excursion , incretins and pancreatic hormone secretion in elderly people with newly diagnosed type 2 diabetes mellitus ( T2DM ) and to study the effects of sitagliptin on glycemic excursion in these subjects . A total of 129 newly diagnosed T2DM patients were enrolled in the study from March 2012 to August 2013 . Clinical data , serum incretin , pancreatic hormone and continuous glucose monitoring data were collected . Among these subjects , elderly patients ( NEDM ) r and omly received metformin combined with sitagliptin phosphate or glimepiride for 24 weeks . The blood glucose , glycosylated hemoglobin A1c ( GHbA1c ) , serum incretins and pancreatic hormone levels were determined . During the oral glucose tolerance test ( OGTT ) , 30 min insulin and C-peptide levels , 120 min insulin levels and ratio of the increases of insulin and blood glucose levels after 30 min of sugar loading ( ∆Ins30/∆Glu30 ) were significantly lower in elderly patients than in middle-aged patients ( P glucagon elevation at 30 min was higher and the glucagon-like peptide-1 ( GLP-1 ) at 30 min was lower in the elderly patients ( P , including the st and ard deviation of the average blood glucose , intraday mean average glucose excursions ( MAGE ) , and mean of daily differences ( MODD ) , were significantly higher in the elderly patients ( P OGTT , insulin , C-peptide and ∆Ins30/∆Glu30 results at 30 min and GLP-1 levels at 120 min in NEDM subjects were significantly increased ( P at 30 min was significantly lower after sitagliptin treatment ( P with glimepiride . Moreover , MAGE and MODD were significantly lower in the sitagliptin group after treatment compared to those in the glimepiride group ( P . No severe hypoglycemia or cardiovascular diseases were observed . Strong blood glucose excursions occur in elderly patients with newly diagnosed T2DM . Sitagliptin phosphate combined with metformin effectively and safely improves glycemic excursion and carbohydrate metabolism in NEDM patients by promoting the first phase of insulin and incretin secretion and inhibiting glucagon secretion of", "BACKGROUND In patients with type 2 diabetes , intensive blood-glucose control with insulin or sulphonylurea therapy decreases progression of microvascular disease and may also reduce the risk of heart attacks . This study investigated whether intensive glucose control with metformin has any specific advantage or disadvantage . METHODS Of 4075 patients recruited to UKPDS in 15 centres , 1704 overweight ( > 120 % ideal bodyweight ) patients with newly diagnosed type 2 diabetes , mean age 53 years , had raised fasting plasma glucose ( FPG ; 6.1 - 15.0 mmol/L ) without hyperglycaemic symptoms after 3 months ' initial diet . 753 were included in a r and omised controlled trial , median duration 10.7 years , of conventional policy , primarily with diet alone ( n=411 ) versus intensive blood-glucose control policy with metformin , aim ing for FPG below 6 mmol/L ( n=342 ) . A secondary analysis compared the 342 patients allocated metformin with 951 overweight patients allocated intensive blood-glucose control with chlorpropamide ( n=265 ) , glibenclamide ( n=277 ) , or insulin ( n=409 ) . The primary outcome measures were aggregates of any diabetes-related clinical endpoint , diabetes-related death , and all-cause mortality . In a supplementary r and omised controlled trial , 537 non-overweight and overweight patients , mean age 59 years , who were already on maximum sulphonylurea therapy but had raised FPG ( 6.1 - 15.0 mmol/L ) were allocated continuing sulphonylurea therapy alone ( n=269 ) or addition of metformin ( n=268 ) . FINDINGS Median glycated haemoglobin ( HbA1c ) was 7.4 % in the metformin group compared with 8.0 % in the conventional group . Patients allocated metformin , compared with the conventional group , had risk reductions of 32 % ( 95 % CI 13 - 47 , p=0.002 ) for any diabetes-related endpoint , 42 % for diabetes-related death ( 9 - 63 , p=0.017 ) , and 36 % for all-cause mortality ( 9 - 55 , p=0.011 ) . Among patients allocated intensive blood-glucose control , metformin showed a greater effect than chlorpropamide , glibenclamide , or insulin for any diabetes-related endpoint ( p=0.0034 ) , all-cause mortality ( p=0.021 ) , and stroke ( p=0.032 ) . Early addition of metformin in sulphonylurea-treated patients was associated with an increased risk of diabetes-related death ( 96 % increased risk [ 95 % CI 2 - 275 ] , p=0.039 ) compared with continued sulphonylurea alone . A combined analysis of the main and supplementary studies showed fewer metformin-allocated patients having diabetes-related endpoints ( risk reduction 19 % [ 2 - 33 ] , p=0.033 ) . Epidemiological assessment of the possible association of death from diabetes-related causes with the concurrent therapy of diabetes in 4416 patients did not show an increased risk in diabetes-related death in patients treated with a combination of sulphonylurea and metformin ( risk reduction 5 % [ -33 to 32 ] , p=0.78 ) . INTERPRETATION Since intensive glucose control with metformin appears to decrease the risk of diabetes-related endpoints in overweight diabetic patients , and is associated with less weight gain and fewer hypoglycaemic attacks than are insulin and sulphonylureas , it may be the first-line pharmacological therapy of choice in these patients", "AIMS To compare the effect of a dipeptidyl peptidase-4 inhibitor ( DPP4-i ) and a sulfonylurea ( SU ) on daily glucose fluctuation in drug-naïve Japanese patients with type 2 diabetes mellitus ( T2DM ) . MATERIAL S AND METHODS A total of 53 drug-naïve Japanese patients with T2DM ( HbA1c , 7.0%-9.0 % ; fasting plasma glucose , 6.1 mmol/L or higher ) were r and omly assigned to either sitagliptin 50 mg qd or glibenclamide 2.5 mg per day ( given in divided doses ) in a 1:1 ratio . A continuous glucose monitoring ( CGM ) device was used to obtain 24-hour glucose profiles for each patient at baseline and at Week 2 . The primary study endpoint was change from baseline in mean amplitude of glucose excursion ( MAGE ) during a 24-hour period . A key secondary endpoint was change from baseline in the st and ard deviation ( SD ) of 24-hour glucose levels . RESULTS After 2 weeks of treatment , a numerically greater reduction in MAGE from baseline was observed in the sitagliptin group compared with the glibenclamide group , but the between-treatment difference was not statistically significant ( LS mean difference [ 95 % CI ] : -0.48 mmol/L [ -1.31 , 0.34 ] ; P = .245 ) . However , a significantly greater reduction in the change from baseline in SD was observed in the sitagliptin group compared with the glibenclamide group ( LS mean difference [ 95 % CI ] : -0.33 mmol/L [ -0.62 , -0.03 ] ; P = .029 ) . CONCLUSIONS This study suggests that the DPP4 inhibitor sitagliptin has a greater ability to reduce daily glucose fluctuation than the SU glibenclamide in drug-naïve Japanese patients with T2DM . Clinical Trials.gov : NCT02318693", "This article introduces the approach of GRADE to rating quality of evidence . GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . \" Quality \" as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence", "Abstract Objective : To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes . Design : Prospect i ve observational study . Setting : 23 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Participants : 4585 white , Asian Indian , and Afro-Caribbean UKPDS patients , whether r and omised or not to treatment , were included in analyses of incidence ; of these , 3642 were included in analyses of relative risk . Outcome measures : Primary predefined aggregate clinical outcomes : any end point or deaths related to diabetes and all cause mortality . Secondary aggregate outcomes : myocardial infa rct ion , stroke , amputation ( including death from peripheral vascular disease ) , and microvascular disease ( predominantly retinal photo-coagulation ) . Single end points : non-fatal heart failure and cataract extraction . Risk reduction associated with a 1 % reduction in up date d mean HbA1c adjusted for possible confounders at diagnosis of diabetes . Results : The incidence of clinical complications was significantly associated with glycaemia . Each 1 % reduction in up date d mean HbA1c was associated with reductions in risk of 21 % for any end point related to diabetes ( 95 % confidence interval 17 % to 24 % , P deaths related to diabetes ( 15 % to 27 % , P myocardial infa rct ion ( 8 % to 21 % , P microvascular complications ( 33 % to 41 % , P patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia . Any reduction in HbA1c is likely to reduce the risk of complications , with the lowest risk being in those with HbA1c values in the normal range ( < 6.0 % )", "OBJECTIVES We sought to assess the prognostic utility of brachial artery reactivity ( BAR ) in patients at risk of cardiovascular events . BACKGROUND Impaired flow-mediated vasodilation measured by BAR is a marker of endothelial dysfunction . Brachial artery reactivity is influenced by risk factors and is responsive to various pharmacological and other treatments . However , its prognostic importance is uncertain , especially relative to other predictors of outcome . METHODS A total of 444 patients were prospect ively enrolled to undergo BAR and follow-up . These patients were at risk of cardiovascular events , based on the presence of risk factors or known or suspected cardiovascular disease . We took a full clinical history , performed BAR , and obtained carotid intima-media thickness ( IMT ) and left ventricular mass and ejection fraction . Patients were followed up for cardiovascular events and all-cause mortality . Multivariate Cox regression analysis was performed to assess the independent association of investigation variables on outcomes . RESULTS The patients exhibited abnormal BAR ( 5.2 + /- 6.1 % [ mean + /- SD ] ) but showed normal nitrate-mediated dilation ( 9.9 + /- 7.2 % ) and normal mean IMT ( 0.67 + /- 0.12 mm [ average ] ) . Forty-nine deaths occurred over the median follow-up period of 24 months ( interquartile range 10 to 34 ) . Patients in the lowest tertile group of BAR ( events than those in the combined group of highest and mid-tertiles ( p = 0.029 , log-rank test ) . However , mean IMT ( rather than flow-mediated dilation ) was the vascular factor independently associated with mortality , even in the subgroup ( n = 271 ) with no coronary artery disease and low risk . CONCLUSIONS Brachial artery reactivity is lower in patients with events , but is not an independent predictor of cardiovascular outcomes in this cohort of patients", "ABSTRACT Objective : To compare the effects of either vildagliptin or glimepiride on glycemic variability , oxidative stress , and endothelial parameters in patients with type 2 diabetes mellitus ( T2DM ) inadequately controlled with metformin alone . Methods : In this r and omized , open-label , parallel study , 34 patients with T2DM being treated with metformin having an HbA1c of 7.0–10.0 % were allocated into either the vildagliptin or glimepiride group . A mixed-meal tolerance test and 72-hour continuous glucose monitoring were conducted , and urinary 8-iso-prostagl and inF2α ( PGF2α ) and endothelial-dependent flow-mediated dilatation ( FMD ) were evaluated at baseline and after 12 weeks of treatment . Results : Similar significant improvements in HbA1c level were shown in both vildagliptin ( −0.8 % ) and glimepiride ( −0.9 % ) groups after treatment ( Ps The mean amplitude of glycemic excursions ( MAGE ) and the mean of daily differences ( MODD ) were significantly decreased by vildagliptin ( P = 0.044 and P = 0.031 , respectively ) but not by glimepiride . Glimepiride was significantly associated with a higher incidence of hypoglycemia than vildagliptin ( P = 0.005 ) . There were no significant differences in urinary 8-iso-PGF2α or FMD between the two groups . Conclusions : Vildagliptin effectively improved glucose level with a significantly greater reduction in glycemic variability and hypoglycemia than glimepiride in patients with T2DM ongoing metformin therapy . The two drugs showed no significant differences in urinary 8-iso-PGF2α and FMD . Trial registration :", "OBJECTIVE Evaluate the effects of two dipeptidyl peptidase-IV ( DPP-4 ) inhibitors , sitagliptin and vildagliptin , known to have different efficacy on mean amplitude of glycemic excursions ( MAGE ) , on oxidative stress , and on systemic inflammatory markers in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS A prospect i ve , r and omized , open-label PROBE design ( parallel group with a blinded end point ) study was performed in 90 patients with type 2 diabetes inadequately controlled by metformin . The study assigned 45 patients to receive sitagliptin ( 100 mg once daily ; sitagliptin group ) and 45 patients to receive vildagliptin ( 50 mg twice daily ; vildagliptin group ) for 12 weeks . MAGE , evaluated during 48 h of continuous subcutaneous glucose monitoring , allowed an assessment of daily glucose fluctuations at baseline and after 12 weeks in all patients . Assessment of oxidative stress ( nitrotyrosine ) and systemic levels of inflammatory markers interleukin (IL)-6 and IL-18 was performed at baseline and after 12 weeks in all patients . RESULTS HbA1c , fasting and postpr and ial glucose , MAGE , and inflammatory and oxidative stress markers were similar between the groups at baseline . After 12 weeks , MAGE ( P vildagliptin group than in the sitagliptin group . After treatment , HbA1c and postpr and ial glucose evidence d similar changes between the groups ( P = NS ) . Vildagliptin treatment was associated with a stronger decrease in nitrotyrosine ( P IL-6 ( P and IL-18 ( P sitagliptin treatment . Nitrotyrosine and IL-6 changes significantly correlated with changes in MAGE but not in fasting glucose and HbA1c . CONCLUSIONS MAGE reduction is associated with reduction of oxidative stress and markers of systemic inflammation in type 2 diabetic patients . These effects were greater in the vildagliptin group than in the sitagliptin group", "BACKGROUND In patients with type 2 diabetes , the effects of intensive glucose control on vascular outcomes remain uncertain . METHODS We r and omly assigned 11,140 patients with type 2 diabetes to undergo either st and ard glucose control or intensive glucose control , defined as the use of gliclazide ( modified release ) plus other drugs as required to achieve a glycated hemoglobin value of 6.5 % or less . Primary end points were composites of major macrovascular events ( death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke ) and major microvascular events ( new or worsening nephropathy or retinopathy ) , assessed both jointly and separately . RESULTS After a median of 5 years of follow-up , the mean glycated hemoglobin level was lower in the intensive-control group ( 6.5 % ) than in the st and ard-control group ( 7.3 % ) . Intensive control reduced the incidence of combined major macrovascular and microvascular events ( 18.1 % , vs. 20.0 % with st and ard control ; hazard ratio , 0.90 ; 95 % confidence interval [ CI ] , 0.82 to 0.98 ; P=0.01 ) , as well as that of major microvascular events ( 9.4 % vs. 10.9 % ; hazard ratio , 0.86 ; 95 % CI , 0.77 to 0.97 ; P=0.01 ) , primarily because of a reduction in the incidence of nephropathy ( 4.1 % vs. 5.2 % ; hazard ratio , 0.79 ; 95 % CI , 0.66 to 0.93 ; P=0.006 ) , with no significant effect on retinopathy ( P=0.50 ) . There were no significant effects of the type of glucose control on major macrovascular events ( hazard ratio with intensive control , 0.94 ; 95 % CI , 0.84 to 1.06 ; P=0.32 ) , death from cardiovascular causes ( hazard ratio with intensive control , 0.88 ; 95 % CI , 0.74 to 1.04 ; P=0.12 ) , or death from any cause ( hazard ratio with intensive control , 0.93 ; 95 % CI , 0.83 to 1.06 ; P=0.28 ) . Severe hypoglycemia , although uncommon , was more common in the intensive-control group ( 2.7 % , vs. 1.5 % in the st and ard-control group ; hazard ratio , 1.86 ; 95 % CI , 1.42 to 2.40 ; P gliclazide ( modified release ) and other drugs as required , that lowered the glycated hemoglobin value to 6.5 % yielded a 10 % relative reduction in the combined outcome of major macrovascular and microvascular events , primarily as a consequence of a 21 % relative reduction in nephropathy . ( Clinical Trials.gov number , NCT00145925 .", "BACKGROUND This study aim ed to compare the effects of sitagliptin on glycemic change and 24-h blood glucose variability with those of the sulfonylurea glimepiride . SUBJECTS AND METHODS A 4-week r and omized double blind-labeled prospect i ve design was used . We recruited 33 patients who had been treated with metformin for at least 2 months . Each participant prescribed with metformin was r and omly assigned to either the sitagliptin ( 100 mg ) or the glimepiride ( 2 mg ) group . Continuous glucose monitoring ( CGM ) was used to monitor glycemic changes for 3 successive days in both groups at baseline and at the 4-week follow-up . Glycemic changes and glucose variability were obtained using CGM , and these data were averaged over all subjects . RESULTS The comparison of glycated hemoglobin ( HbA1c ) between baseline and the 4-week follow-up showed that HbA1c was significantly reduced in the sitagliptin group ( 7.0 ± 0.5 % to 6.6 ± 0.4 % , P the glimepiride group ( 7.3 ± 0.4 % to 6.9 ± 0.4 % , P The sitagliptin and glimepiride groups had similar HbA1c levels after 4 weeks , and there were no significant differences between the two groups . The mean amplitude of glycemic excursions ( MAGE ) decreased significantly in the sitagliptin group ( 4.9 ± 1.0 to 3.7 ± 0.9 mmol/L , P observed in the glimepiride group ( 5.7 ± 1.5 to 5.0 ± 1.4 mmol/L , P=0.175 ) . The SD and oxidative stress markers did not differ significantly between the two groups . CONCLUSIONS When sitagliptin was combined with metformin , the patients showed much more efficient blood glucose controlling effects , not only the three indexes of fasting blood glucose , postpr and ial blood glucose , and glycated hemoglobin , but also MAGE" ]	41188f06-06ff-11f0-808a-c43d1ab1c353
This is the protocol for a review and there is no abstract . The objectives are as follows : To identify and assess the effectiveness of interventions to improve adherence to iron chelation therapy compared to st and ard care in people with SCD or thalassaemia including : identifying and assessing the effectiveness of different types of interventions ( psychological and psychosocial , educational , medication interventions , or multi-component interventions ) ; identifying and assessing the effectiveness of interventions specific to different age groups ( children , adolescents , adults )	[ "Background Thalassaemia major ( TM ) patients need regular blood transfusions that lead to accumulation of iron and death from heart failure . Deferiprone has been reported to be superior to deferoxamine for the removal of cardiac iron and improvement in left ventricular ( LV ) function but little is known of their relative effects on the right ventricle ( RV ) , which is being increasingly recognised as an important prognostic factor in cardiomyopathy . Therefore data from a prospect i ve r and omised controlled trial ( RCT ) comparing these chelators was retrospectively analysed to assess the RV responses to these drugs . Methods In the RCT , 61 TM patients were r and omised to receive either deferiprone or deferoxamine monotherapy , and CMR scans for T2 * and cardiac function were obtained . Data were re-analysed for RV volumes and function at baseline , and after 6 and 12 months of treatment . Results From baseline to 12 months , deferiprone reduced RV end systolic volume ( ESV ) from 37.7 to 34.2 mL ( p = 0.008 ) , whilst RV ejection fraction ( EF ) increased from 69.6 to 72.2 % ( p = 0.001 ) . This was associated with a 27 % increase in T2 * ( p increase in LVEF ( p deferoxamine showed no change in RVESV ( 38.1 to 39.1 mL , p = 0.38 ) , or RVEF ( 70.0 to 69.9 % , p = 0.93 ) whereas the T2 * increased by 13 % ( p change in LVEF ( 0.32 % ; p = 0.66 ) . Analysis of between drugs treatment effects , showed significant improvements favouring deferiprone with a mean effect on RVESV of -1.82 mL ( p = 0.014 ) and 1.16 % for RVEF ( p = 0.009 ) . Using regression analysis the improvement in RVEF at 12 months was shown to be greater in patients with lower baseline EF values ( p RVEF of 3.5 % favouring deferiprone over deferoxamine ( p = 0.012 ) . Conclusion In this retrospective analysis of a prospect i ve RCT , deferiprone monotherapy was superior to deferoxamine for improvement in RVEF and end-systolic volume . This improvement in the RV volumes and function may contribute to the improved cardiac outcomes seen with deferiprone", "BACKGROUND Thalassemia major is the most common genetic disorder in Pakistan . The study was done to compare the efficacy and safety of the deferiprone with deferrioxamine for the treatment of iron overload in children with thalassemia major . METHODS This r and omized controlled trail was conducted at thalassemia blood transfusion unit of Allied Hospital , Faisalabad (AHF)/District Headquarter Hospital ( DHQ ) , Faisalabad . Thalassemia-Unit Hilal-e-Ahmar , Alizeb Foundation and Blood Bank Services Faisalabad from November 2010 to December 2011.Children with beta thalassemia major of age more than 2 years and less than 16 years with transfusion iron over load were r and omly allocated to one of the two groups each comprising of 67 patients . One group received deferiprone given at a daily dose of 75mg/kg in three divided doses orally while the other group received deferrioxamine at dose 50 mg/kg/24hrs for 5 days/week as parental infusion . Changes in the serum ferritin level were assessed . Cardiac function and toxicity were also examined . RESULTS Serum ferritin was significantly reduced after 1 year in both treatment arms ( p=0.01 ) . Neutropenia observed in 13 ( 19.40 % ) non-splenectomized patients taking deferiprone . Transient elevations in ALT were observed in 3 ( 4.47 % ) children taking deferiprone . Left ventricular ejection fraction ( LVEF ) remained in normal range in both treatment arm but has decreased significantly in Deferrioxamine group compliance . Compliance was better in deferiprone as compared to deferrioxamine . Discontinuing percentage 2 ( 3 % ) vs 9 ( 13.43 % ) . CONCLUSION Deferiprone is a highly efficacious and safe chelation therapy for patients with thalassemia major who are non-compliant to Deferrioxamine . Deferiprone have an efficacy profile comparable to st and ard Deferrioxamine", "Patients with thalassemia major requiring regular blood transfusions accumulate iron that is toxic to the heart , liver , and endocrine systems . The following prospect i ve , r and omized trial was carried out to determine the effectiveness , in children and young adults , of combined deferiprone ( DFP ) and deferoxamine ( DFO ) in reducing transfusional iron overload compared to either drug alone and to assess the safety and tolerability of DFP . Sixty-six patients were r and omized into three treatment arms : daily DFP combined with DFO twice weekly ; daily DFP only ; and DFO only 5 days/week . Fifty-six patients completed the 54 weeks and were assessed by different indices . A significant reduction of liver iron concentration and serum ferritin was observed in all three arms while significant reduction of liver iron score was observed in patients on combination therapy only . Cardiac function did not significantly change in any arm . Compliance improved in patients who received combined therapy . Toxicity of DFP was mild to moderate and acceptable ; most commonly , transient arthropathy and nausea/vomiting were observed . Thus , combination therapy has shown to be effective in reducing iron overload in thalassemia patients", "Background — Cardiac complications secondary to iron overload are the leading cause of death in & bgr;-thalassemia major . Approximately two thirds of patients maintained on the parenteral iron chelator deferoxamine have myocardial iron loading . The oral iron chelator deferiprone has been demonstrated to remove myocardial iron , and it has been proposed that in combination with deferoxamine it may have additional effect . Methods and Results — Myocardial iron loading was assessed with the use of myocardial T2 * cardiovascular magnetic resonance in 167 patients with thalassemia major receiving st and ard maintenance chelation monotherapy with subcutaneous deferoxamine . Of these patients , 65 with mild to moderate myocardial iron loading ( T2 * 8 to 20 ms ) entered the trial with continuation of subcutaneous deferoxamine and were r and omized to receive additional oral placebo ( deferoxamine group ) or oral deferiprone 75 mg/kg per day ( combined group ) . The primary end point was the change in myocardial T2 * over 12 months . Secondary end points of endothelial function ( flow-mediated dilatation of the brachial artery ) and cardiac function were also measured with cardiovascular magnetic resonance . There were significant improvements in the combined treatment group compared with the deferoxamine group in myocardial T2 * ( ratio of change in geometric means 1.50 versus 1.24 ; P=0.02 ) , absolute left ventricular ejection fraction ( 2.6 % versus 0.6 % ; P=0.05 ) , and absolute endothelial function ( 8.8 % versus 3.3 % ; P=0.02 ) . There was also a significantly greater improvement in serum ferritin in the combined group ( −976 versus −233 & mgr;g/L ; P of deferoxamine , combination treatment with additional deferiprone reduced myocardial iron and improved the ejection fraction and endothelial function in thalassemia major patients with mild to moderate cardiac iron loading", "Most deaths in beta-thalassemia major result from cardiac complications due to iron overload . Differential effects on myocardial siderosis may exist between different chelators . A r and omized controlled trial was performed in 61 patients previously maintained on subcutaneous deferoxamine . The primary end point was the change in myocardial siderosis ( myocardial T2 ( * ) ) over 1 year in patients maintained on subcutaneous deferoxamine or those switched to oral deferiprone monotherapy . The dose of deferiprone was 92 mg/kg/d and deferoxamine was 43 mg/kg for 5.7 d/wk . Compliance was 94 % + /- 5.3 % and 93 % + /- 9.7 % ( P = .81 ) , respectively . The improvement in myocardial T2 ( * ) was significantly greater for deferiprone than deferoxamine ( 27 % vs 13 % ; P = .023 ) . Left ventricular ejection fraction increased significantly more in the deferiprone-treated group ( 3.1 % vs 0.3 % absolute units ; P = .003 ) . The changes in liver iron level ( -0.93 mg/g dry weight vs -1.54 mg/g dry weight ; P = .40 ) and serum ferritin level ( -181 microg/L vs -466 microg/L ; P = .16 ) , respectively , were not significantly different between groups . The most frequent adverse events were transient gastrointestinal symptoms for deferiprone-treated patients and local reactions at the infusion site for deferoxamine . There were no episodes of agranulocytosis . Deferiprone monotherapy was significantly more effective than deferoxamine over 1 year in improving asymptomatic myocardial siderosis in beta-thalassemia major", "Summary . Desferrioxamine ( DFX ) alone ( 40–50 mg/kg/d s.c . over 8–12 h , five times weekly ) was compared with combined DFX twice weekly and deferiprone ( 75 mg/kg/d ) over 12 months in previously poorly chelated thalassaemia patients . Serum ferritin fell from 5506 ± 635 µg/l ( mean ± SEM ) to 3998 ± 604 µg/l ( P ) in the DFX group and from 4153 ± 517 µg/l to 2805 ± 327 µg/l in the combined group ( P Deferiprone plus DFX produced a greater mean urine iron excretion ( 1·01 mg/kg/24 h ) than iron intake from blood transfusion in each patient . Main side‐effects were skin reactions ( DFX alone ) , nausea and arthralgia ( combined therapy ) . As chelation therapy , the combined protocol was as effective as DFX five times weekly", "The objective of this study was to compare the short- and long-term efficacy of deferoxamine ( DFO ) given by subcutaneous ( SC ) continuous infusion over 10 hours via a pump ( n = 10 ) versus a twice-daily subcutaneous bolus injection of the same overall dose ( n = 10 ) in 20 thalassemic children . Urinary iron excretion was measured in 24-hour urine sample s after DFO treatment in the 20 patients . The patients were r and omized to two groups : 10 patients continued SC continuous infusion with a pump and the remaining 10 received the same overall dose of DFO by twice-daily SC bolus injection for a year . Serum ferritin levels and T1-weighted spin-echo and T2-weighted fast spin-echo signal intensities of liver and paraspinal muscle were determined at initiation and 1 year after initiation of the therapy . In 12 patients , six from each group , liver biopsies were performed and hepatic iron concentration was determined at initiation of therapy and 1 year after treatment . A similar and significant decrease in ferritin levels and improvement in signal intensities of the liver were observed in response to chelation therapy with DFO in both groups ( P Hepatic iron concentration decreased in all patients in the SC bolus injection group ( P 0.05 ) . Hepatic iron concentration was noted to be slightly increased in two patients in the SC continuous infusion group , which may be due to poor compliance . Based on these results , twice-daily SC bolus injection of DFO is as effective as administration via SC continuous infusion using a pump . Subcutaneous bolus injection , being more convenient for the patient , may be a more preferable method of DFO administration", "Once‐daily deferasirox dispersible tablets ( DT ) have a well‐defined safety and efficacy profile and , compared with parenteral deferoxamine , provide greater patient adherence , satisfaction , and quality of life . However , barriers still exist to optimal adherence , including gastrointestinal tolerability and palatability , leading to development of a new film‐coated tablet ( FCT ) formulation that can be swallowed with a light meal , without the need to disperse into a suspension prior to consumption . The r and omized , open‐label , phase II ECLIPSE study evaluated the safety of deferasirox DT and FCT formulations over 24 weeks in chelation‐naïve or pre‐treated patients aged ≥10 years , with transfusion‐dependent thalassemia or IPSS‐R very‐low‐ , low‐ , or intermediate‐risk myelodysplastic syndromes . One hundred seventy‐three patients were r and omized 1:1 to DT ( n = 86 ) or FCT ( n = 87 ) . Adverse events ( overall ) , consistent with the known deferasirox safety profile , were reported in similar proportions of patients for each formulation ( DT 89.5 % ; FCT 89.7 % ) , with a lower frequency of severe events observed in patients receiving FCT ( 19.5 % vs. 25.6 % DT ) . Laboratory parameters ( serum creatinine , creatinine clearance , alanine aminotransferase , aspartate aminotransferase and urine protein/creatinine ratio ) generally remained stable throughout the study . Patient‐reported outcomes showed greater adherence and satisfaction , better palatability and fewer concerns with FCT than DT . Treatment compliance by pill count was higher with FCT ( 92.9 % ) than with DT ( 85.3 % ) . This analysis suggests deferasirox FCT offers an improved formulation with enhanced patient satisfaction , which may improve adherence , thereby reducing frequency and severity of iron overload‐related complications ", " Deferasirox is a once‐daily , oral iron chelator developed for treating transfusional iron overload . Pre clinical studies indicated that the kidney was a potential target organ of toxicity . As patients with sickle cell disease often have abnormal baseline renal function , the primary objective of this r and omised , open‐label , phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population . Assessment of efficacy , as measured by change in liver iron concentration ( LIC ) using biosusceptometry , was a secondary objective . A total of 195 adult and paediatric patients received deferasirox ( n = 132 ) or deferoxamine ( n = 63 ) . Adverse events most commonly associated with deferasirox were mild , including transient nausea , vomiting , diarrhoea , abdominal pain and skin rash . Abnormal laboratory studies with deferasirox were occasionally associated with mild non‐progressive increases in serum creatinine and reversible elevations in liver function tests . Discontinuation rates from deferasirox ( 11·4 % ) and deferoxamine ( 11·1 % ) were similar . Over 1 year , similar dose‐dependent LIC reductions were observed with deferasirox and deferoxamine . Once‐daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease", "BACKGROUND AND OBJECTIVES Deferasirox ( ICL670 ) is a novel once-daily oral iron chelator developed for the treatment of chronic iron overload from blood transfusions . This study evaluated the safety and tolerability of deferasirox in pediatric patients with transfusion-dependent beta-thalassemia major . Efficacy and pharmacokinetic assessment s were secondary objectives . DESIGN AND METHODS Forty patients equally stratified into two age groups -- children ( 2 to treated with deferasirox for 48 weeks . All received once-daily deferasirox 10 mg/kg/day with modifications allowed after 12 weeks ' treatment . Safety , liver iron concentration ( LIC ) , serum ferritin and pharmacokinetics were assessed . RESULTS Thirty-nine patients completed the study . One withdrew due to a skin rash . Adverse events were typical of this population , but only four were considered related to the study drug : mild nausea ( two adolescents ) and moderate skin rash ( two children ) . There were no serious adverse events related to the study drug . Five patients briefly interrupted treatment due to elevated transaminases with no recurrences when treatment resumed . The mean deferasirox dose was 11.3 mg/kg/day . Overall LIC increased gradually from week 12 as mean daily iron intake was higher than excretion . Steady-state plasma levels of deferasirox and its iron complex , Fe-[deferasirox]2 , were comparable between children and adolescents . INTERPRETATION AND CONCLUSIONS Deferasirox was well tolerated by this pediatric population . Toxicities known to be associated with other commercially available iron chelators were not observed . The dose employed was too low to induce a net negative iron balance in this regularly transfused population . Pharmacokinetic data support a once-daily dosing regimen based on body weight", "Introduction Iron overload is the primary cause of mortality and morbidity in thalassemia major ( TM ) despite advances in chelation therapy . The aim of this study was to compare the effectiveness and safety of deferasirox ( DFX ) and deferoxamine ( DFO ) as iron-chelating agents in patients with transfusion-dependent β-thalassemia major . Methods This prospect i ve r and omized study included 60 patients with transfusion-dependent β-TM during the period from September 2014 to September 2015 . Their ages were ≥ 6 years , and they had serum ferritin above 1500 μg/L and were on irregular DFO therapy . Patients had regular packed red cell transfusion in a dose of 10 mL/kg/session . They were r and omized to receive DFX ( single oral daily dose of 20–40 mg/kg/day ) or DFO ( 20–50 mg/kg/day via subcutaneous infusion over 8–10 hours , 5 days a week ) . Iron overload was determined by serum ferritin level . The primary endpoint was decrease of serum ferritin level below 1500 μg/L. The secondary endpoint was drug safety . Results Both drugs significantly reduced serum ferritin ( p in serum ferritin levels ( p = 0.673 ) and in percent reduction of ferritin ( p = 0.315 ) . There were no significant differences between the two groups in the total amount of blood transfusion ( p = 0.166 ) and average iron intake ( p = 0.227 ) . There were no mortalities or any serious adverse effects , neutropenia , arthropathy , or pulmonary toxicity . Gastrointestinal upset and skin rash occurred more frequently with DFX than with DFO ( p = 0.254 and 0.095 , respectively ) . Conclusion With appropriate dosing and compliance with drugs , both DFX and DFO are generally well tolerated , safe , and effective in reducing serum ferritin levels in iron-overloaded , regularly-transfused thalassemia major patients . Therefore , oral DFX is recommended for more convenience and adherence to the treatment regimen", "Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies", "To date , there is a lack of long‐term safety and efficacy data for iron chelation therapy in transfusion‐dependent patients with sickle cell disease ( SCD ) . To evaluate the long‐term safety and efficacy of deferasirox ( a once‐daily oral iron chelator ) , patients with SCD completing a 1‐year , Phase II , r and omized , deferoxamine (DFO)‐controlled study entered a 4‐year extension , continuing to receive deferasirox , or switching from DFO to deferasirox . Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose , 33·5 % completed the 5‐year study . The most common reasons for discontinuation were withdrawal of consent ( 23·8 % ) , lost to follow‐up ( 9·2 % ) and adverse events ( AEs ) ( 7·6 % ) . Investigator‐assessed drug‐related AEs were predominantly gastrointestinal [ including nausea ( 14·6 % ) , diarrhoea ( 10·8 % ) ] , mild‐to‐moderate and transient in nature . Creatinine clearance remained within the normal range throughout the study . Despite conservative initial dosing , serum ferritin levels in patients with ≥4 years deferasirox exposure significantly decreased by −591 μg/l ( 95 % confidence intervals , −1411 , −280 μg/l ; P = 0·027 ; n = 67 ) . Long‐term deferasirox treatment for up to 5 years had a clinical ly acceptable safety profile , including maintenance of normal renal function , in patients with SCD . Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years", "Background In patients hospitalized over a 4 year period for pulmonary embolism ( PE ) , we assessed relationships of testosterone ( TT ) and estrogen therapy ( ET ) anteceding PE in patients found to have familial-acquired thrombophilia . Methods From 2011 through 2014 , 347 patients were hospitalized in Cincinnati Mercy Hospitals with PE . Retrospective chart review was used to identify patients receiving TT or ET before PE ; coagulation studies were done prospect ively if necessary . Results Preceding hospitalization for PE , 8 of 154 men ( 5 % ) used TT , and 24 of 193 women ( 12 % ) used ET . The median number of months from the initiation of TT or ET to development of PE was 7 months in men and 18 months in women . Of the 6 men having coagulation measures , all had ≥ 1 thrombophilia , and of the 18 women having measures of coagulation , 16 had ≥ 1 thrombophilia . The sensitivity of a previous history of thrombosis to predict PE was low , 25 % ( 2/8 men ) , 4 % ( 1/24 women ) . Conclusions Of 154 men hospitalized for PE , 8 ( 5 % ) used TT , and of 193 women , 24 ( 12 % ) used ET . Our data suggests that PE is an important complication of TT in men and ET in women , in part reflecting an interaction between familial and acquired thrombophilia and exogenous hormone use", "Background / Aims : There is increasing evidence demonstrating the value of transfusions in sickle cell disease ( SCD ) . However , result ant iron overload can be life threatening if untreated . Chelation therapy with deferoxamine requires parenteral infusions that can negatively impact quality of life and adherence to treatment . Methods : As part of a phase II trial , SCD patient-reported outcomes were evaluated . One hundred and ninety-five patients were r and omized ( 2:1 ) to receive oral deferasirox ( 5–30 mg/kg/day ) or deferoxamine ( 20–50 mg/kg , 5 days per week ) ; 121 had previously received deferoxamine . Results : At each time point , significantly more patients who had previously received deferoxamine were ‘ satisfied/very satisfied ’ with deferasirox , or found treatment to be ‘ convenient/very convenient ’ compared with deferoxamine ( p fewer hours were lost from daily activities with deferasirox than deferoxamine treatment . Most patients ( 77 % ) preferred deferasirox , and more were willing to continue taking deferasirox than deferoxamine at end-of- study ( 84 vs. 11 % , respectively ) . Conclusions : Patients with SCD are therefore more satisfied with deferasirox , which has a lower impact on daily activities than deferoxamine . Given the high levels of satisfaction , it is likely that quality of life will be improved . These results also suggest that treatment adherence with deferasirox may be better than with deferoxamine , which should lead to improved long-term outcomes ", "OBJECTIVE Ascertainment of an appropriate strategy of iron chelation for multi-transfused thalassemic children in developing countries . DESIGN Prospect i ve study from May 2000 to April 2001 . SETTING Urban tertiary care center . METHODS Thirty thalassemic children having received more than 20 blood transfusions and a serum ferritin greater than 1500 ng/ml were enrolled and r and omized into three groups . Group I received desferrioxamine ( DFX ) at a dose of 40 mg/kg subcutaneously , 5 days/week . Children in group II received oral deferiprone ( L1 ) at a dose of 75 mg/kg/day daily and group III received a combination of daily L1 at a dose of 75 mg/kg/day and DFX at a dose of 40 mg/kg/day two times per week . The assessment of chelation was done by 24-hr urinary iron excretion ( UIE ) and measurement of serum ferritin levels at start and after 6 months of follow up . Statistical difference of serum ferritin levels between the three groups was assessed by applying analysis of variance . Analysis of covariance was applied to find out the urinary iron excretion keeping serum ferritin values same in each groups . RESULTS Ferritin levels after 6 months of intervention were maximally decreased in group I. There was a significant difference between groups I and II however , no difference was noted between groups I and group III . There was no statistically significant difference in mean urinary iron excretion by keeping the initial serum ferritin levels equal though it was found to be more in group III as compared to other groups . CONCLUSIONS DFX is the most effective chelating drug in iron overloaded multi-transfused thalassemic patients . In view of cost and unacceptability of daily DFX injections , combination therapy is an effective method of chelation thus increasing the compliance and cost effectiveness . Deferiprone ( L1 ) alone is not an effective mode of chelation when used for a short period", "Background and Objectives The aim of this prospect i ve , r and omized , 1-year study was to compare the efficacy and safety of oral deferiprone ( DFP ) with those of combinations of parenteral desferrioxamine ( DFO ) with oral DFP . Design and Methods A total of 24 patients with thalassemia major were r and omized to receive one of the following two treatments ; DFP given at a daily dose of 75 mg/kg in combination with DFO ( 40–50 mg/kg twice weekly ) ( n=12 ) or as single agent ( n=12 ) . In addition , 12 patients treated with 40–50 mg/kg DFO 5 days weekly were included as a reference group without r and omization . Changes in liver iron concentration ( LIC ) and serum ferritin ( SF ) were assessed ; total iron excretion ( TIE ) , urinary iron excretion ( UIE ) and iron balance were calculated . Cardiac function and toxicity were also examined . Design and Methods SF and LIC were significantly reduced after 1 year of combination therapy ( p=0.01 and 0.07 , respectively ) . A decrease of LIC was observed in all but one patient ( 87.5 % ) following the combination therapy but in only 42 % of patients treated with DFP monotherapy . In the DFO reference group , a statistically significant decrease in LIC ( p=0.01 ) associated with a substantial decrease in SF ( p=0.08 ) was observed after 1 year . The combination regimen result ed in greater TIE compared to DFP monotherapy ( p=0.08 ) and was the regimen associated with the highest iron balance compared to DFP monotherapy ( p=0.04 ) or st and ard DFO treatment ( p=0.006 ) . Interpretations and Conclusions The addition of subcutaneous DFO twice weekly to oral DFP 75 mg/kg is a highly efficacious and safe chelation therapy providing superior chelation activity to that of DFP and likely has an efficacy profile comparable to that of st and ard DFO ", "In β-thalassemia major ( β-TM ) patients , iron chelation therapy is m and atory to reduce iron overload secondary to transfusions . Recommended first line treatment is deferoxamine ( DFO ) from the age of 2 and second line treatment after the age of 6 is deferiprone ( L1 ) . A multicenter r and omized open-label trial was design ed to assess the effectiveness of long-term alternating sequential L1-DFO vs. L1 alone iron chelation therapy in β-TM patients . Deferiprone 75 mg/kg 4 days/week and DFO 50 mg/kg/day for 3 days/week was compared with L1 alone 75 mg/kg 7 days/week during a 5-year follow-up . A total of 213 thalassemia patients were r and omized and underwent intention-to-treat analysis . Statistically , a decrease of serum ferritin level was significantly higher in alternating sequential L1-DFO patients compared with L1 alone patients ( p = 0.005 ) . Kaplan-Meier survival analysis for the two chelation treatments did not show statistically significant differences ( log-rank test , p = 0.3145 ) . Adverse events and costs were comparable between the groups . Alternating sequential L1-DFO treatment decreased serum ferritin concentration during a 5-year treatment by comparison to L1 alone , without significant differences of survival , adverse events or costs . These findings were confirmed in a further 21-month follow-up . These data suggest that alternating sequential L1-DFO treatment may be useful for some β-TM patients who may not be able to receive other forms of chelation treatment", "The efficacy of a eutectic mixture of local anesthetics ( EMLA ) in alleviating the pain associated with subcutaneous needle insertion for infusion of the iron-chelating agent , deferoxamine , was examined in 12 patients with homozygous beta-thalassemia . As reported by the patient using a 100-mm visual analogue scale , the pain of insertion was rated as significantly less after application of EMLA ( mean + /- SD , 1.5 + /- 2.2 mm ) than the pain associated with needle insertion without EMLA ( 34.8 + /- 33.5 mm , P = .005 ) . Subsequently , in a double-blind r and omized trial of 10 beta-thalassemia patients , EMLA was significantly better ( 5.7 + /- 8.2 mm ) than placebo ( 27.0 + /- 22.8 mm , P = .01 ) in reducing the pain of needle insertion for deferoxamine infusion . No adverse effects were reported with the use of EMLA cream . These results suggest that EMLA may be effective in reducing the pain associated with needle insertion for subcutaneous deferoxamine infusion in beta-thalassemia patients , which may lead to improved compliance with this irritating , prolonged therapy . The safety of EMLA use in these patients , and others receiving regular parenteral therapy , should now be examined", "Summary This report up date s the combined experience of four centres involved in the long‐term treatment of transfusional iron overload in 84 patients with the oral iron chelator deferiprone ( L1 ) over 167 patient‐years . The source of L1 was variable , including two university research laboratories and three pharmaceutical firms . Compliance was rated as excellent in 48 % , intermediate in 36 % , and poor in 16 % of patients . On a mean L1 dose of 73–81 mg/kg/d , urinary iron excretion was stable , at around 0 5 mg/kg/d , with no indication of a diminishing response with time . Serum ferritin showed a very steady decrease with time from an initial mean ±1SD of 4207 ±3118 to 1779 ± 1154μg/1 after 48 months ( P patients ab and oned L1 therapy , Major complications of L1 requiring permanent discontinuation of treatment included agranulocytosis ( three ) , severe nausea ( four ) , arthritis ( two ) and persistent liver dysfunction ( one ) . The remaining patients ab and oned treatment because of low compliance ( three ) and conditions unrelated to L1 toxicity ( four ) . Lesser complications permitting continued L1 treatment included transient mild neutropenia ( four ) , zinc deficiency ( 12 ) , transient increase in liver enzymes ( 37 ) , moderate nausea ( three ) and arthropathy ( 17 ) . There was no treatment‐related mortality . Although the complications associated with L1 treatment are significant and require close monitoring , they do not preclude effective long‐term therapy in the vast majority of patients . Further well‐controlled prospect i ve studies of L1 are required in order to enable proper judgement of its suitability for general long‐term clinical use", "OBJECTIVES The r and omized comparison of deferasirox to deferoxamine for myocardial iron removal in patients with transfusion-dependent anemias ( CORDELIA ) gave the opportunity to assess relative prevalence and body distribution of iron overload in screened patients . METHODS Patients aged ≥ 10 yr with transfusion-dependent anemias from 11 countries were screened . Data were summarized descriptively , overall and across regions . RESULTS Among 925 patients ( 99.1 % with β-thalassemia major ; 98.5 % receiving prior chelation ; mean age 19.2 yr ) , 36.7 % had myocardial iron overload ( myocardial T2 * ≤ 20 ms ) , 12.1 % had low left ventricular ejection fraction . Liver iron concentration ( LIC ) ( mean 25.8 mg Fe/g dw ) and serum ferritin ( median 3702 ng/mL ) were high . Fewer patients in the Middle East ( ME ; 28.5 % ) had myocardial T2 * ≤ 20 ms vs. patients in the West ( 45.9 % ) and Far East ( FE , 40.9 % ) . Patients in the West had highest myocardial iron burden , but lowest LIC ( 26.9 % with LIC dw ) and serum ferritin . Among patients with normal myocardial iron , a higher proportion of patients from the ME and FE had LIC ≥ 15 than < 7 mg Fe/g dw ( ME , 56.7 % vs. 17.2 % ; FE , 78.6 % vs. 7.8 % , respectively ) , a trend which was less evident in the West ( 44.6 % vs. 33.9 % , respectively ) . Transfusion and chelation practice s differed between regions . CONCLUSIONS Evidence of substantial myocardial and liver iron burden across regions revealed a need for optimization of effective , convenient iron chelation regimens . Significant regional variation exists in myocardial and liver iron loading that are not well explained ; improved underst and ing of factors contributing to differences in body iron distribution may be of clinical benefit", "Introduction The Satisfaction with Iron Chelation Therapy ( SICT ) instrument was developed based on a literature review , in-depth patient and clinician interviews , and cognitive debriefing interviews . An , open-label , single arm , multicenter trial evaluating the efficacy and safety of deferasirox in patients diagnosed with transfusion-dependent iron overload , provided an opportunity to assess the psychometric measurement properties of the instrument . Methods Psychometric analyses were performed using data at baseline from 273 patients with a range of transfusion-dependent iron overload conditions who were participating in a multinational study . Responsiveness was further evaluated for all patients who also had subsequent satisfaction domain scores collected at week 4 . Results Baseline SICT domain scores had acceptable floor and ceiling effects and internal consistency reliability ( Cronbach ’s alpha : 0.75–0.85 ) . Item discriminant and item convergent validity were both excellent although one item in each analysis did not meet the specified criterion . Small to moderate correlations were observed between SICT and Short Form 36 Health Survey ( SF-36 ) domain scores . Patients with the highest levels of serum ferritin at baseline ( > 3100 ng/mL ) were the least satisfied about the Perceived Effectiveness of ICT and vice versa . Satisfaction improved in all patients , although there were no clear differences observed between groups of patients defined according to changes in serum ferritin levels from baseline to week 4 ( stable , improved , or worsened ) . Conclusions The SICT domains are reliable and valid . Further testing using a more specific criterion ( such as assessing patient global ratings of change in satisfaction domains that correspond to the SICT domains ) could help to establish with greater confidence the responsiveness of the instrument", "A multicentre r and omized open‐label trial was design ed to assess the effectiveness of long‐term sequential deferiprone – deferoxamine ( DFO – DFP ) versus DFP alone to treat thalassaemia major ( TM ) . DFP at 75 mg/kg , divided into three oral daily doses , for 4 d/week and DFO by subcutaneous infusion ( 8–12 h ) at 50 mg/kg per day for the remaining 3 d/week was compared with DFP alone at 75 mg/kg , administered 7 d/week during a 5‐year follow‐up . The main outcome measures were differences between multiple observations of serum ferritin concentrations . Secondary outcomes were survival analysis , adverse events , and costs . Consecutive thalassaemia patients ( 275 ) were assessed for eligibility ; 213 of these were r and omized and underwent intention‐to‐treat analysis . The decrease of serum ferritin levels during the treatment period was statistically significant higher in sequential DFP – DFO patients compared with DFP‐alone patients ( P = 0·005 ) . Kaplan – Meier survival analysis for the two chelation treatments did not show any statistically significant differences ( long‐rank test , P = 0·3145 ) . Adverse events and costs were comparable between the groups . The trial results show that sequential DFP – DFO treatment compared with DFP alone significantly decreased serum ferritin concentration during treatment for 5 years without significant differences regarding survival , adverse events , or costs . This trial was registered at http://www . clinical trials.gov as # NCT00733811", " Iron‐overloaded β‐thalassaemia major ( BTM ) children have high risk of delayed sexual/physical maturation , liver/heart diseases and reduced life expectancy . The lifelong need to use iron chelators , their unpleasant administration , side effects and lack of awareness regarding iron overload risks all hamper BTM patient compliance to iron chelators . This study evaluated the impact of clinical pharmacist‐provided services on the outcome of iron‐overloaded BTM children . Forty‐eight BTM children were r and omly assigned to either control group , who received st and ard medical care , or intervention group , who received st and ard medical care plus clinical pharmacist‐provided services . Services included detection of drug‐related problems ( DRPs ) and their management , patient education regarding disease nature and iron chelators , as well as providing patient‐tailored medication charts . After six months of study implementation , there was a highly significant difference between the control and intervention groups in serum ferritin ( SF ) ( mean : 3871 versus 2362 , μg/l , p = 0.0042 ) , patient healthcare satisfaction ( median : 24.47 versus 90.29 , p ) and quality of life ( QoL ) ( median : 49.84 versus 63.51 , p = 0.0049 ) . The intervention group showed a decline from baseline to the end of study in DRPs ( 64–4 ) , the number of non‐compliant patients ( 24–3 ) and mean SF levels ( 3949–2362 μg/l , p pharmacist‐provided services can positively impact the outcome of BTM children", "In patients with thalassemia intermedia ( TI ) , such as beta‐TI , alpha‐thalassemia ( mainly HbH disease and mild/moderate forms of HbE/beta‐thalassemia ) , iron overload is an important challenge in terms of diagnosis , monitoring , and treatment . Moreover , to date , the only possible chelators available are deferoxamine , deferasirox , and deferiprone . Here , we report the first 5‐year long‐term r and omized clinical trial comparing the effectiveness of deferiprone versus deferoxamine in patients with TI . Body iron burden , which was determined by measuring serum ferritin levels in the same patient over 5 years and analyzed according to the generalized linear mixed model ( GLMM ) , showed a linear decrease over time in the mean serum ferritin levels in both treatment groups ( P‐value = 0.035 ) . The overall period of observation was 235.2 person‐years for the deferiprone patients compared with 214.3 person‐years for the deferoxamine patients . The results of the log‐rank test suggested that the deferiprone treatment did not affect survival compared with the deferoxamine treatment ( P‐value = 0.360 ) . The major adverse events observed included gastrointestinal symptoms and joint pain or arthralgia . Neutropenia and agranulocytosis were also detected , suggesting needing of strict hematological control . In conclusion , long‐term iron chelation therapy with deferiprone is associated with an efficacy and safety similar to that of deferoxamine , suggesting that this drug is an alternative option in cases in which deferoxamine and deferasirox are contraindicated . Am . J. Hematol . 90:634–638 , 2015 . © 2015 Wiley Periodicals ,", " OBJECTIVE Minimal data are available on the combined two oral iron chelators in β-thalassemia major ( β-TM ) . Comparison of safety , efficacy , compliance , treatment satisfaction , and quality of life ( QoL ) of two regimens : deferiprone ( DFP ) and deferoxamine ( DFO ) versus DFP and deferasirox ( DFX ) were studied . METHODS A prospect i ve r and omized trial ( NCT01511848 ) was conducted on 96 young β-TM patients with severe iron overload . Patients were r and omized to receive either DFP with DFO ( arm 1 ) or DFP and DFX ( arm 2 ) . Efficacy endpoints were the difference between two groups in the change of serum ferritin ( SF ) , liver iron concentration ( LIC ) , cardiac MRI , and quality of life ( QoL ) . RESULTS In both arms , SF and LIC at 12 months were significantly lower , and geometric mean cardiac T2 * was higher compared to baseline . On regression analysis of change in each studied variable against time , significant difference between slopes of the two groups regarding cardiac T2 * ( P = 0.001 with more improvement in DFP/DFX patients ) was found with no significant difference in the slopes of SF and LIC ( P = 0.218 and 0.340 ) . CONCLUSION Both iron chelation combination regimens were equally effective in reducing iron overload and improving QoL.DFP/DFX combination proved superior in improving cardiac T2 * , treatment compliance , and patients satisfaction with no greater adverse events ", "R and omized comparison data on the efficacy and safety of deferasirox for myocardial iron removal in transfusion dependent patients are lacking . CORDELIA was a prospect i ve , r and omized comparison of deferasirox ( target dose 40 mg/kg per day ) vs subcutaneous deferoxamine ( 50 - 60 mg/kg per day for 5 - 7 days/week ) for myocardial iron removal in 197 β-thalassemia major patients with myocardial siderosis ( T2 * 6 - 20 milliseconds ) and no signs of cardiac dysfunction ( mean age , 19.8 years ) . Primary objective was to demonstrate noninferiority of deferasirox for myocardial iron removal , assessed by changes in myocardial T2 * after 1 year using a per- protocol analysis . Geometric mean ( Gmean ) myocardial T2 * improved with deferasirox from 11.2 milliseconds at baseline to 12.6 milliseconds at 1 year ( Gmeans ratio , 1.12 ) and with deferoxamine ( 11.6 milliseconds to 12.3 milliseconds ; Gmeans ratio , 1.07 ) . The between-arm Gmeans ratio was 1.056 ( 95 % confidence interval [ CI ] , 0.998 , 1.133 ) . The lower 95 % CI boundary was greater than the prespecified margin of 0.9 , establishing noninferiority of deferasirox vs deferoxamine ( P = .057 for superiority of deferasirox ) . Left ventricular ejection fraction remained stable in both arms . Frequency of drug-related adverse events was comparable between deferasirox ( 35.4 % ) and deferoxamine ( 30.8 % ) . CORDELIA demonstrated the noninferiority of deferasirox compared with deferoxamine for myocardial iron removal . This trial is registered at www . clinical trials.gov as # NCT00600938" ]	41188f42-06ff-11f0-808a-c43d1ab1c353
Background / Objectives : Activity-related energy expenditure ( AEE ) might be an important factor in the etiology of chronic diseases . However , measurement of free-living AEE is usually not feasible in large-scale epidemiological studies but instead has traditionally been estimated based on self-reported physical activity . Recently , accelerometry has been proposed for objective assessment of physical activity , but it is unclear to what extent this methods explains the variance in AEE.Subjects/ Methods : We conducted a systematic review search ing MEDLINE data base ( until 2014 ) on studies that estimated AEE based on accelerometry-assessed physical activity in adults under free-living conditions ( using doubly labeled water method ) . Extracted study characteristics were sample size , accelerometer ( type ( uniaxial , triaxial ) , metrics ( for example , activity counts , steps , acceleration ) , recording period , body position , wear time ) , explained variance of AEE ( R2 ) and number of additional predictors . The relation of univariate and multivariate R2 with study characteristics was analyzed using nonparametric tests . Results : Nineteen articles were identified . Examination of various accelerometers or sub population s in one article was treated separately , result ing in 28 studies . Sample sizes ranged from 10 to 149 . In most studies the accelerometer was triaxial , worn at the trunk , during waking hours and reported activity counts as output metric . Recording periods ranged from 5 to 15 days . The variance of AEE explained by accelerometer-assessed physical activity ranged from 4 to 80 % ( median crude R2=26 % ) . Sample size was inversely related to the explained variance . Inclusion of 1 to 3 other predictors in addition to accelerometer output significantly increased the explained variance to a range of 12.5–86 % ( median total R2=41 % ) . The increase did not depend on the number of added predictors . Conclusions : We conclude that there is large heterogeneity across studies in the explained variance of AEE when estimated based on accelerometry . Thus , data on predicted AEE based on accelerometry-assessed physical activity need to be interpreted cautiously	[ "Symptoms during physical activity and physical inactivity are hallmarks of chronic obstructive pulmonary disease ( COPD ) . Our aim was to evaluate the validity and usability of six activity monitors in patients with COPD against the doubly labelled water ( DLW ) indirect calorimetry method . 80 COPD patients ( mean±sd age 68±6 years and forced expiratory volume in 1 s 57±19 % predicted ) recruited in four centres each wore simultaneously three or four out of six commercially available monitors vali date d in chronic conditions for 14 consecutive days . A priori validity criteria were defined . These included the ability to explain total energy expenditure ( TEE ) variance through multiple regression analysis , using TEE as the dependent variable with total body water ( TBW ) plus several physical activity monitor outputs as independent variables ; and correlation with activity energy expenditure ( AEE ) measured by DLW . The Actigraph GT3X ( Actigraph LLC , Pensacola , FL , USA ) , and DynaPort MoveMonitor ( McRoberts BV , The Hague , the Netherl and s ) best explained the majority of the TEE variance not explained by TBW ( 53 % and 70 % , respectively ) and showed the most significant correlations with AEE ( r=0.71 , p patients with chronic diseases such as COPD . This study vali date s six activity monitors in the field against indirect calorimetry ( DLW ) in patients with COPD", "The use of movement registration for daily physical activity assessment was evaluated during a 7-day period in 30 free-living subjects . Body movement was registered with a Tracmor motion sensor consisting of a triaxial accelerometer and a data unit for on-line processing of accelerometer output over 1-min intervals . Average Tracmor output was correlated against four different energy estimates : 1 ) average daily metabolic rate ( ADMR ) , determined with doubly labeled water ; 2 ) ADMR-sleeping metabolic rate ( SMR ; determined in a respiration chamber ) ; 3 ) ( ADMR-SMR ) per kilogram of body mass ; and 4 ) the overall physical activity level ( PAL = ADMR/SMR ) . The highest correlation was found for the relationship between Tracmor output and PAL ( r = 0.58 ) . After correction for Tracmor values arising from vibrations produced by transportation means , this correlation was improved to 0.73 . There was no difference between Tracmor output and PAL in discriminating between overall activity levels with \" low \" ( PAL 1.85 ) intensity . It is concluded that the Tracmor can be used in free-living subjects to distinguish among interindividual as well as intraindividual levels of daily physical activity", "Background / Objectives : A combined heart rate ( HR ) and motion sensor ( Actiheart ) has been proposed as an accurate method for assessing total energy expenditure ( TEE ) and physical activity energy expenditure ( PAEE ) . However , the extent to which factors such as caffeine may affect the accuracy by which the estimated HR-related PAEE contribution will affect TEE and PAEE estimates is unknown . Therefore , we examined the validity of Actiheart in estimating TEE and PAEE in free-living adults under a caffeine trial compared with doubly labeled water ( DLW ) as reference criterion . Subjects/ Methods : Using a double-blind crossover trial ( Clinical trials.gov ID : # NCT01477294 ) with two conditions ( 4-day each with a 3-day-washout period ) , r and omly ordered as caffeine ( 5 mg/kg per day ) and placebo ( malt-dextrine ) intake , TEE was measured by DLW in 17 physically active men ( 20–38 years ) who were non-caffeine users . In each condition , resting energy expenditure ( REE ) was assessed by indirect calorimetry and PAEE was calculated as ( TEE−(REE+0.1 TEE ) ) . Simultaneously , PAEE and TEE were estimated by Actiheart using an individual calibration ( ACC+HRstep ) . Results : Under caffeine , ACC+HRstep explained 76 and 64 % of TEE and PAEE from DLW , respectively ; corresponding results for the placebo condition were 82 and 66 % . No mean bias was found between ACC+HRstep and DLW for TEE ( caffeine:-468 kJ per day ; placebo:-407 kJ per day ) , although PAEE was slightly underestimated ( caffeine:-856 kJ per day ; placebo:-1147 kJ per day ) . Similar limits of agreement were observed in both conditions ranging from −2066 to 3002 and from −3488 to 1776 kJ per day for TEE and PAEE , respectively . Conclusions : Regardless of caffeine intake , the combined HR and motion sensor is valid for estimating free-living energy expenditure in a group of healthy men but is less accurate for an individual assessment", "We assessed the ability of the Polar activity recorder ( AR ) to measure energy expenditure ( EE ) during military training . Twenty-four voluntary male conscripts participated in the study and wore an AR on the non-dominant wrist 24 h a day for 7 d. The AR analyzed and stored the frequency of h and movements ( f_h and ) into memory at 1 min intervals . The relationship between f_h and and EE was studied over a 7 d period of military training using the doubly labeled water ( DLW ) technique . In addition , the relationship between f_h and and EE was analyzed during walking and running on a treadmill with an indirect calorimeter ( IC ) , and f_h and was measured during a supervised 45 min field march test where the conscripts carried combat gear . EE was expressed as physical activity level ( PAL ) , total energy expenditure ( TEE ) , and activity-induced energy expenditure adjusted for body mass ( AEE/BM ) . Over the 7 d period , f_h and alone explained 46 % of inter-individual variation in PAL(DLW ) . After inclusion of body height and mass in the model used to predict PAL(DLW ) from f_h and , a very high positive correlation and a low st and ard error of estimate ( SEE ) were observed between the AR and DLW techniques : for TEE r = 0.86 ( p with PAL(IC ) ( r = 0.97 ± 0.02 ) . In the 45 min field march test , the AR measured similar f_h and as on the treadmill at the same speed . In conclusion , the wrist-worn AR can be regarded as a reliable and valid method for assessing EE during intensive training", "OBJECTIVE The objective was to evaluate two accelerometers , the RT3 and the TriTrac-R3D for their ability to produce estimates of physical activity-related energy expenditure ( PAEE ) in overweight/obese adults . RESEARCH METHODS AND PROCEDURES PAEE estimates from both accelerometers were obtained in two experiments . In Experiment 1 , 13 overweight/obese subjects ( BMI 34.2+/-6.4 kg/m2 ) were monitored over 2 weeks in everyday life , PAEE being simultaneously measured by the doubly labeled water method ( DLW ) . In Experiment 2 , 8 overweight/obese subjects ( BMI 34.3+/-5.0 kg/m2 ) and 10 normal-weight subjects ( BMI 20.8+/-2.1 kg/m2 ) were monitored during a treadmill walking protocol , PAEE being simultaneously measured by indirect calorimetry . RESULTS In Experiment 1 , there was no significant difference between methods in mean PAEE ( DLW : 704+/-223 kcal/d , RT3 : 656+/-140 kcal/d , TriTrac-R3D 624+/-419 kcal/d ) . The relative difference between methods ( accelerometer vs. DLW ) was -17.1%+/-16.7 % for the RT3 and -20.0+/-44.6 % for the TriTrac-R3D . Correlation for PAEE between RT3 and DLW was higher than between TriTrac-R3D and DLW ( r=0.67 , p 95 % confidence interval ( CI ) ( kcal/d ) of the mean difference between methods was large , amounting to -385 to 145 for the RT3 and -887 to 590 for the TriTrac-R3D . In Experiment 2 , both accelerometers were sensitive to the changes in treadmill speed , with no significant difference in mean PAEE between methods in overweight/obese subjects . CONCLUSIONS Although both accelerometers did not provide accurate estimates of PAEE at individual levels , the data suggest that RT3 has the potential to assess PAEE at group levels in overweight/obese subjects", "Background Current research practice employs wide-ranging accelerometer wear time criteria to identify a valid day of physical activity ( PA ) measurement . Objective To evaluate the effects of varying amounts of daily accelerometer wear time on PA data . Methods A total of 1000 days of accelerometer data from 1000 participants ( age=38.7±14.3 years ; body mass index=28.2±6.7 kg/m2 ) were selected from the 2005–2006 National Health and Nutrition Examination Study data set . A reference data set was created using 200 r and om days with 14 h/day of wear time . Four additional sample s of 200 days were r and omly selected with a wear time of 10 , 11 , 12 and 13 h/day1 . These data sets were used in day-to-day comparison to create four semisimulation data sets ( 10 , 11 , 12 , 13 h/day ) from the reference data set . Differences in step count and time spent in inactivity ( ) intensity PA were assessed using repeated- measures analysis of variance and absolute percent error ( APE ) . Results There were significant differences for moderate intensity PA between the reference data set and semisimulation data sets of 10 and 11 h/day . Differences were observed in 10–13 h/day1 for inactivity and light intensity PA , and 10–12 h/day for steps ( all p values increased with shorter wear time ( 13 h/day=3.9–14.1 % ; 12 h/day=9.9–15.2 % , 11 h/day=17.1–35.5 % ; 10 h/day=24.6–40.3 % ) . Discussion These data suggest that using accelerometer wear time criteria of 12 h/day or less may underestimate step count and time spent in various PA levels " ]	41188f7e-06ff-11f0-808a-c43d1ab1c353
Context The metabolism of thyroid hormones , which are essential for normal development , involves many proteins and enzymes . It requires iodine as a key component but is also influenced by several other micronutrients , including selenium , zinc , iron , and vitamin A. Objective This systematic review was design ed to investigate the effect of micronutrient status and supplementation on iodine status and thyroid hormone concentrations . Data Sources Using the PRISMA ( Preferred Reporting Items for Systematic Review s and Meta- Analysis ) guidelines , electronic data bases were search ed from their inception to April 2016 . Study Selection Human studies published in English and reporting data on micronutrient status and iodine status and /or thyroid hormone concentrations were included . Studies that examined the effect of micronutrient supplementation on iodine status and /or thyroid hormone concentrations were also included . Data Extraction A pre design ed and piloted data extraction form was used to compile data from individual studies . Results A total of 57 studies were included : 20 intervention studies and 37 observational studies . Although observational evidence suggests that concentrations of selenium , zinc , and iron are positively associated with iodine status , data from r and omized controlled trials fail to confirm this relationship . Conclusions Further studies are needed to provide greater underst and ing of the role of micronutrient status in iodine nutrition and thyroid function to ascertain the public health implication s for population s worldwide	[ "Objective : Vitamin A and its retinoid derivates play an important role in regulation of normal growth and development . Vitamin A has been shown to regulate thyroid hormone metabolism and inhibit thyroid-stimulating hormone ( TSH ) secretion via down regulation of TSH-β gene expression ; however , the effect of vitamin A on thyroid function in obese individuals who are at higher risk of sub clinical hypothyroidism is still unclear . In the present study we investigate the impact of vitamin A supplementation on thyroid function in obese women . Method : A 4-month r and omized , double blind controlled trial was conducted among 84 healthy women aged 17–50 years old : 56 were obese ( body mass index [ BMI ] 30–35 kg/m2 ) and 28 were nonobese ( BMI 18.5–24.9 kg/m2 ) . Obese women were r and omly allocated to receive either vitamin A ( 25,000 IU/d retinyl palmitate ) or placebo . Nonobese women received vitamin A. At baseline and 4 months after intervention , serum concentrations of TSH , total thyroxine ( T4 ) , total triiodothyronine ( T3 ) , retinol-binding protein ( RBP ) , and transthyretin ( TTR ) were measured . Results : Baseline concentrations of thyroid hormones , RBP and TTR were not significantly different between groups . Vitamin A caused a significant reduction in serum TSH concentrations in obese ( p = 0.004 ) and nonobese ( p = 0.001 ) groups . Serum T3 concentrations also increased in both obese and nonobese vitamin A – treated groups ( p 0.001 ) . Serum T4 decreased in all 3 groups after treatment . The results showed a significant reduction in serum RBP in the obese group after vitamin A supplementation ( p = 0.007 ) , but no significant change was seen in serum TTR . Conclusions : Serum TSH concentrations in vitamin A – treated subjects were significantly reduced ; therefore , vitamin A supplementation might reduce the risk of sub clinical hypothyroidism in premenopausal women", "OBJECTIVE In many developing countries , children are at high risk for both goiter and anemia . Iron ( Fe ) deficiency adversely effects thyroid metabolism and reduces efficacy of iodine prophylaxis in areas of endemic goiter . The study aim was to determine if co-fortification of iodized salt with Fe would improve efficacy of the iodine in goitrous children with a high prevalence of anemia . DESIGN AND METHODS In a 9-month , r and omized , double-blind trial , 6 - 15 year-old children ( n=377 ) were given iodized salt ( 25 microg iodine/g salt ) or dual-fortified salt with iodine ( 25 microg iodine/g salt ) and Fe ( 1 mg Fe/g salt , as ferrous sulfate microencapsulated with partially hydrogenated vegetable oil ) . RESULTS In the dual-fortified salt group , hemoglobin and Fe status improved significantly compared with the iodized salt group ( P mean decrease in thyroid volume measured by ultrasound in the dual-fortified salt group ( -38 % ) was twice that of the iodized salt group ( -18 % ) ( P serum thyroxine was significantly increased ( P prevalence of hypothyroidism and goiter decreased ( P efficacy of iodine in goitrous children with a high prevalence of anemia", "BACKGROUND AND OBJECTIVE A nationwide survey of schoolchildren was conducted to detect regional differences in urinary iodine excretion in Latvia and to compare the results with data from the newborn thyroid-stimulating hormone ( TSH ) screening data base as well with the results of a similar study performed in Latvia 10 years ago . MATERIAL S AND METHODS We conducted a cross-sectional school-based cluster survey of 915 children aged 9 - 12 years in 46 r and omly selected schools in all regions of Latvia . Urine sample s , question naires on the consumption of iodized salt and information on socioeconomic status were collected . TSH levels in newborns were also measured . RESULTS The median creatinine-st and ardized urinary iodine concentration ( UIC ) in our study was 107.3μg/g Cr . UIC measurements indicative of mild iodine deficiency were present in 31.6 % , moderate deficiency in 11.9 % and severe deficiency in 2.8 % of the participants . The prevalence of iodine deficiency was the highest in the southeastern region of Latgale and the northeastern region of Vidzeme . The prevalence of TSH values > 5mIU/L followed a similar pattern . The self-reported prevalence of regular iodized salt consumption was 10.2 % . Children from urban schools had a significantly lower UIC than children from rural schools . CONCLUSIONS Our findings suggest that although the overall median UIC in Latvian schoolchildren falls within the lower normal range , almost 50 % of the schoolchildren are iodine deficient , especially in urban schools and in the eastern part of Latvia . The absence of a m and atory salt iodization program puts a significant number of children and pregnant women at risk", "BACKGROUND Dual fortification of salt with iodine and iron could be a sustainable approach to combating iodine and iron deficiencies . OBJECTIVE We compared the efficacy of dual-fortified salt ( DFS ) made by using 2 proposed contrasting formulas-one fortifying with iron as micronized ground ferric pyrophosphate ( MGFePP ) and the other with iron as encapsulated ferrous fumarate (EFF)-with the efficacy of iodized salt ( IS ) in schoolchildren in rural southern India . DESIGN After stability and acceptability testing , a double-blind , household-based intervention was conducted in 5 - 15-y-old children ( n = 458 ) r and omly assigned into 3 groups to receive IS or DFS with iron as MGFePP or EFF , both at 2 mg/g salt . We measured hemoglobin , iron status , and urinary iodine at baseline , 5 mo , and 10 mo . RESULTS Median serum ferritin and calculated median body iron improved significantly in the 2 groups receiving iron . After 10 mo , the prevalence of anemia decreased from 16.8 % to 7.7 % in the MGFePP group ( P median urinary iodine concentration increased significantly in the IS and EFF groups ( P iodine in salt with 1.8 % moisture were high for MGFePP , whereas the EFF segregated in salt with 0.5 % moisture and caused color changes in some local foods . CONCLUSIONS Both DFSs were efficacious in reducing the prevalence of anemia and iron deficiency in school-age children . Local salt characteristics should be taken into consideration when choosing an iron fortificant for DFS to achieve optimal iodine stability and color", "BACKGROUND In many developing countries , children are at high risk of both goiter and iron deficiency anemia . Iron deficiency adversely affects thyroid metabolism and may reduce the efficacy of iodine prophylaxis in areas of endemic goiter . OBJECTIVE The aim of this study was to determine whether iron supplementation in goitrous , iron-deficient children would improve their response to iodized salt . DESIGN We conducted a r and omized , double-blind , placebo-controlled trial in 5 - 14-y-old children in Côte d'Ivoire . Goitrous , iron-deficient children ( n = 166 ) consuming iodized salt ( 10 - 30 mg I/kg salt at the household level ) were supplemented with either iron ( 60 mg Fe/d , 4 d/wk for 16 wk ) or placebo . At 0 , 1 , 6 , 12 , and 20 wk , we measured hemoglobin , serum ferritin , serum transferrin receptor , whole-blood zinc protoporphyrin , thyrotropin , thyroxine , urinary iodine , and thyroid gl and volume ( by ultrasonography ) . RESULTS Hemoglobin and iron status at 20 wk were significantly better after iron treatment than after placebo ( P mean reduction in thyroid size in the iron-treated group was nearly twice that in the placebo group ( x + /- SD percentage change in thyroid volume from baseline : -22.8 + /- 10.7 % compared with -12.7 + /- 10.1 % ; P goiter prevalence was 43 % in the iron-treated group compared with 62 % in the placebo group ( P whole-blood thyrotropin or serum thyroxine at baseline or during the intervention . CONCLUSIONS Iron supplementation improves the efficacy of iodized salt in goitrous children with iron deficiency . A high prevalence of iron deficiency among children in areas of endemic goiter may reduce the effectiveness of iodine prophylaxis", "BACKGROUND Thyroid function depends on the essential trace mineral selenium , which is at the active center of the iodothyronine deiodinase enzymes that catalyze the conversion of the prohormone thyroxine ( T(4 ) ) to the active form of thyroid hormone , triiodothyronine ( T(3 ) ) . OBJECTIVE Because selenium intake in the United Kingdom has fallen during the past 25 y , we wanted to determine whether current selenium status might be limiting conversion of T(4 ) to T(3 ) in the elderly , in whom marginal hypothyroidism is relatively common . DESIGN We investigated the effect of selenium supplementation in a double-blind , placebo-controlled trial in 501 elderly UK volunteers . Similar numbers of men and women from each of 3 age groups , 60 - 64 y , 65 - 69 y , and 70 - 74 y , were r and omly allocated to receive 100 , 200 , or 300 microg Se/d as high-selenium yeast or placebo yeast for 6 mo . As part of the study , plasma selenium , thyroid-stimulating hormone , and total and free T(3 ) and T(4 ) were measured . Data from 368 euthyroid volunteers who provided blood sample s at baseline and 6 mo were analyzed . RESULTS Although selenium status at baseline correlated weakly with free T(4 ) ( r = -0.19 , P ratio of free T(3 ) to free T(4 ) ( r = 0.12 , P = 0.02 ) , we found no evidence of any effect of selenium supplementation on thyroid function , despite significant increases in plasma selenium . However , baseline plasma selenium in our study ( x : 91 microg/L ) was somewhat higher than in previous supplementation studies in which apparently beneficial effects were seen . CONCLUSION We found no indication for increasing selenium intake to benefit T(4 ) to T(3 ) conversion in the elderly UK population", "BACKGROUND Vitamin A ( VA ) deficiency ( VAD ) and iodine deficiency ( ID ) often coexist in children in Africa . VAD may affect thyroid function and the response to iodine prophylaxis . OBJECTIVE The aim was to investigate the effects of supplementation with iodine or VA alone , and in combination , in children with concurrent VAD and ID . DESIGN A 6-mo r and omized , double-blind , 2 x 2 intervention trial was conducted in 5 - 14 y-old South African children ( n = 404 ) , who , on average , had mild-to-moderate VAD and ID . At baseline and after 3 mo , children received 1 ) iodine ( 191 mg I as oral iodized oil ) + placebo ( IS group ) , 2 ) VA ( 200000 IU VA as retinyl palmitate ) + placebo ( VAS group ) , 3 ) both iodine and VA ( IS+VAS group ) , or 4 ) placebo . At baseline , 3 mo , and 6 mo , urinary iodine ( UI ) , thyroid volume , thyrotropin ( thyroid-stimulating hormone ; TSH ) , total thyroxine ( TT(4 ) ) , thyroglobulin , serum retinol ( SR ) , and retinol-binding protein ( RBP ) were measured . RESULTS SR and RBP increased significantly with VA supplementation ( P UI , SR , and RBP , there were no significant treatment interactions between iodine and vitamin A. The 3-factor and all three 2-factor interactions were significant for thyroid volume , TSH , and thyroglobulin ( P TT(4 ) . There was a clear effect of VAS without IS on TSH , thyroglobulin , and thyroid volume ; all 3 variables decreased significantly ( P VA supplements are effective in treating VAD in areas of mild ID and have an additional benefit-through suppression of the pituitary TSHbeta gene , VAS can decrease excess TSH stimulation of the thyroid and thereby reduce the risk of goiter and its sequelae", "Objectives To assess iodine and iron nutritional status among Nepalese school children . Methods A cross-sectional , community based study was conducted in the two districts , Ilam ( hilly region ) and Udayapur ( plain region ) of eastern Nepal . A total of 759 school children aged 6–13 y from different schools within the study areas were r and omly enrolled . A total of 759 urine sample s and 316 blood sample s were collected . Blood hemoglobin level , serum iron , total iron binding capacity and urinary iodine concentration was measured . Percentage of transferrin saturation was calculated using serum iron and total iron binding capacity values . Results The mean level of hemoglobin , serum iron , total iron binding capacity , transferrin saturation and median urinary iodine excretion were 12.29 ± 1.85 g/dl , 70.45 ± 34.46 μg/dl , 386.48 ± 62.48 μg/dl , 19.94 ± 12.07 % and 274.67 μg/L respectively . Anemia , iron deficiency and iodine deficiency ( urinary iodine excretion Insufficient urinary iodine excretion ( urinary iodine excretion Iron deficiency and anemia are common in Nepalese children , whereas , iodine nutrition is more than adequate . Low urinary iodine excretion was common in iron deficiency and anemia", "Purpose Selenium is an essential trace mineral and a component of selenoproteins that are involved in the production of thyroid hormones and in regulating the immune response . We aim ed to explore the effect of low-dose selenium supplementation on thyroid peroxidase antibody ( TPO-Ab ) concentration and thyroid function in pregnant women from a mild-to-moderate iodine-deficient population . Methods Sample s and data were from a secondary analysis of Selenium in PRegnancy INTervention ( SPRINT ) , a double-blind , r and omized , placebo-controlled study that recruited 230 women with singleton pregnancies from a UK antenatal clinic at 12 weeks of gestation . Women were r and omized to receive 60 µg/day selenium or placebo until delivery . Serum thyroid peroxidase antibodies ( TPO-Ab ) , thyrotropin ( TSH ) and free thyroxine ( FT4 ) were measured at 12 , 20 and 35 weeks and thyroglobulin antibodies ( Tg-Ab ) at 12 weeks . Results 93.5 % of participants completed the study . Se supplementation had no more effect than placebo in decreasing TPO-Ab concentration or the prevalence of TPO-Ab positivity during the course of pregnancy . In women who were either TPO-Ab or Tg-Ab negative at baseline ( Thy-Ab−ve ) , TSH increased and FT4 decreased significantly throughout gestation ( P baseline , TSH tended to decrease and was lower than placebo at 35 weeks ( P = 0.050 ) . FT4 fell more on Se than placebo supplementation and was significantly lower at 35 weeks ( P = 0.029 ) . Conclusions Low-dose selenium supplementation in pregnant women with mild-to-moderate deficiency had no effect on TPO-Ab concentration , but tended to change thyroid function in Thy-Ab+ve women", "OBJECTIVE To investigate the relationship between selenium status , thyroid Volume and gl and echostructure . DESIGN Cross-sectional . METHODS In 792 men ( 45 - 60 Years ) and 1108 women ( 35 - 60 Years ) from the SU.VI.MAX study , thyroid Volume and gl and echostructure were determined ultrasonographically . At baseline , thyrotropin , free thyroxine , selenium , zinc , alpha-tocopherol , beta-carotene , retinol , urinary iodine and thiocyanate concentrations were measured . Alcohol consumption , smoking , and menopausal status were assessed by a question naire . A stepwise linear and a logistic regression model were used , adjusting for antioxidant vitamins , trace elements status and age . RESULTS In women , there was an inverse association between selenium status and thyroid Volume ( P=0.003 ) . A protective effect of selenium against goiter ( odds ratio (OR)=0.07 , 95 % confidence interval (CI)=0.008 - 0.6 ) and thyroid tIssue damage ( OR=0.2 , 95 % CI=0.06 - 0.7 ) was observed . There was no evidence of an association between menopausal status and other antioxidant elements , thyroid Volume or thyroid hypoechogenicity . Smoking , but not alcohol consumption , was associated with an increased risk of thyroid enlargement in women ( OR=3.94 , 95 % CI=1.64 - 9.48 ) . No association between thyroid Volume , thyroid structure or selenium was found in men . CONCLUSION Our findings suggest that selenium may protect against goiter . Selenium was related to thyroid echostructure , suggesting it may also protect against autoimmune thyroid disease", "Extensive data from animal and human studies indicate that iron deficiency impairs thyroid metabolism . The aim of this study was to determine thyroid hormone status in iron-deficient adolescent girls . By stepwise r and om sampling from among all public high schools for girls in Lar and its vicinity in southern Iran , 103 out of 431 iron deficient subjects were selected . Urine and serum sample s were collected and assayed for urinary iodine and serum ferritin , iron , total iron binding capacity ( TIBC ) , thyroid stimulating hormone ( TSH ) , thyroxine ( T4 ) , triiodothyronine ( T3 ) , free thyroid hormones ( fT4 and fT3 ) , triiodothyronine resin uptake ( T3RU ) , reverse triiodothyronine ( rT3 ) , selenium and albumin concentrations . Hematological indices for iron status confirmed that all subjects were iron-deficient . There was a significant correlation between T4 and ferritin ( r = 0.52 , P TSH and ferritin ( r = -0.3 , P ratio of T3/T4 ( r = -0.42 , P rT3 concentration ( r = -0.35 , P thyroid hormone status in iron-deficient adolescent girls", "Selenium has important roles as an antioxidant , in thyroid hormone metabolism , redox reactions , reproduction and immune function , but information on the selenium status of Thai children is limited . We have assessed the selenium status of 515 northeast Thai children ( 259 males ; 256 females ) aged 6 to 13 years from 10 rural schools in Ubon Ratchthani province . Serum selenium ( n=515 ) was analyzed by Graphite Furnace Atomic Absorption Spectrophotometry and dietary selenium intake by Hydride Generation Absorption Spectrophotometry from one-day duplicate diet composites , from 80 ( 40 females ; 40 males ) r and omly selected children . Inter-relationships between serum selenium and selenium intakes , and other biochemical micronutrient indices were also examined . Mean ( SD ) serum selenium was 1.46 ( 0.24 ) micro mol/L. Concentrations were not affected by infection or haemoglobinopathies , but were dependent on school ( P children had serum selenium concentrations indicative of clinical selenium deficiency ( i.e. serum selenium and serum zinc ( r= 0.216 ; P serum retinol ( r = 0.273 ; P urinary iodine ( r = -0.110 ; P = 0.014 ) , haemoglobin ( r = 0.298 ; P haematocrit ( r = 0.303 ; P Mean ( SD ) dietary selenium intake was 46 ( 22 ) micro g/d . Children with low serum selenium concentrations had a lower mean selenium intake than those with high serum selenium concentrations ( 38 + /- 17 vs.51 + /- 24 micro g/d ; P < 0.010 ) . In conclusion , there appears to be no risk of selenium deficiency among these northeast Thai children", "Selenium ( Se ) is a key component of iodinases ; higher Se levels are associated with lower titers of antithyroid peroxidase antibodies ( anti-TPO ) . Pregnancy exerts profound effects on thyroid function and autoimmunity . To assess the relationship of urine Se levels with thyroid function and autoimmunity in pregnant women residing in Athens , Greece , we studied prospect ively 47 euthyroid women in uncomplicated singleton pregnancies ( mean age + SD : 30 + 5 years ) in each trimester , measuring urine Se levels , urine iodine , plasma thyrotropin ( TSH ) , free thyroxine and triiodothyronine ( FT4 and FT3 ) , as well as levels of anti-TPO antibodies . Changes of the measured parameters were assessed over each trimester ; thyroid parameters were assessed with relation to Se levels . Urine Se dropped by the third trimester , whereas urine iodine did not change appreciably during pregnancy . TSH and anti-TPO did not show appreciable changes ; FT4 and FT3 gradually decreased as the pregnancy advanced . No relationship between urine Se levels and anti-TPO was found . During pregnancy , changes in urine Se levels accompany mild changes in thyroid function . However , we did not find some association between these changes and thyroid autoimmune activity over this period , probably because the effect of Se on thyroid autoimmunity may only become apparent in case of excess Se fortification", "Iodothyronine 5′ deiodinase , which is mainly responsible for peripheral T3 production , has recently been demonstrated to be a selenium (Se)-containing enzyme . The structure of nuclear thyroid hormone receptors contains Zinc ( Zn ) ions , crucial for the functional properties of the protein . In the elderly , reduced peripheral conversion of T4 to T3 with a lower T3/T4 ratio and overt hypothyroidism are frequently observed . We measured serum Se and RBC GSH-Px ( as indices of Se status ) , circulating and RBC Zinc ( as indices of Zn status ) , thyroid hormones and TSH in 109 healthy euthyroid subjects ( 52 women , 57 men ) , carefully selected to avoid abnormally low thyroid hormone levels induced by acute or chronic diseases or calorie restriction . The subjects were subdivided into three age groups . To avoid under- or malnutrition conditions , dietary records were obtained for a sample of 24 subjects , r and omly selected and representative of the whole population for age and sex . Low T3/T4 ratios and reduced Se and RBC GSH-Px activity were observed only in the older group . A highly significant linear correlation between the T3/T4 ratio and indices of Se status was observed in the older group of subjects ( r=0.54;p . Indices of Zn status did not correlate with thyroid hormones , but RBC Zn was decreased in older as compared with younger subjects . We concluded that reduced peripheral T4 conversion is related to impaired Se status in the elderly", "OBJECTIVE The existence of concurrent micronutrient deficiencies in Indian women of reproductive age has received little attention . This study aim ed to comprehensively assess the micronutrient status of nonpregnant rural and tribal women 18 - 30 y from central India . METHODS Participants ( n = 109 ) were r and omly selected using a stratified ( rural-tribal ) proportionate-to- population size cluster sampling method from 12 subcenters in Ramtek block , Nagpur . Sociodemographic , anthropometric , dietary , and biochemical data , including blood and urine sample s , were obtained . RESULTS Tribal and rural women had similar sociodemographic characteristics and anthropometric status ; 63 % of women had a body mass index median urinary iodine concentration was 215 μg/L ( IQR : 127 , 319 ) . The mean ( SD ) concentration of hemoglobin , serum zinc , retinol , and folate was 112 ( 13 ) g/L , 10.8 ( 1.6 ) μmol/L , 1.2 ( 0.3 ) μmol/L , 18.4 ( 8.4 ) nmol/L , respectively , with a geometric mean serum vitamin B(12 ) concentration of 186 pmol/L. The percentage of women with low values for hemoglobin ( 120 g/L ) , serum zinc ( vitamin B(12 ) ( retinol ( and folate ( Tribal women had a higher prevalence of zinc deficiency ( 58 % versus 39 % , P = 0.054 ) and concurrent deficiency of any two micronutrients ( 46 % versus 26 % ; P = 0.034 ) , including zinc and anemia ( 38 % versus 21 % , P = 0.024 ) . CONCLUSION Zinc , vitamin B(12 ) , and iron constitute the principal micronutrient deficiencies in these women . Existing supplementation programs should be extended to include 18- to 30-y-old nonpregnant women as the majority of childbearing occurs within this timeframe", "Poor iron status affects 50 % of Indian women and compromises work productivity , cognitive performance , and reproduction . Among the many strategies to reduce iron deficiency is the commercial fortification of iodized table salt with iron to produce a double-fortified salt ( DFS ) . The objective of this study was to test the efficacy of DFS in reducing iron deficiency in rural women of reproductive age from northern West Bengal , India . The participants were 212 women between 18 and 55 y of age who worked as full-time tea pickers on a large tea estate . Participants in the r and omized , controlled , double-blind study were assigned to use either DFS or a control iodized salt for 7.5 to 9 mo . The DFS was fortified with 3.3-mg ferrous fumarate ( 1.1-mg elemental iron ) per kg of iodized salt , whereas the control salt contained only iodine ( 47 mg/kg potassium io date ) , and both salt varieties were distributed gratis to the families of participants at 0.5 kg/mo for each 2 household members . At baseline , 53 % of participants were anemic ( hemoglobin iron deficient ( serum ferritin iron-deficient anemic . Also , 22 % had a transferrin receptor concentration > 8.6 mg/L and 22 % had negative ( ) body iron stores . After 9 mo the participants receiving DFS showed significant improvements compared with controls in hemoglobin ( + 2.4 g/L ) , ferritin ( + 0.13 log10 μg/L ) , soluble transferrin receptor ( −0.59 mg/L ) , and body iron ( + 1.43 mg/kg ) , with change in status analyzed by general linear models controlling for baseline values . This study demonstrated that DFS is an efficacious approach to improving iron status and should be further evaluated for effectiveness in the general population . This trial was registered at clinical trials.gov as NCT01032005", "OBJECTIVE The iodine status of a population is traditionally evaluated by either urinary iodine ( UI ) excretion or by some measure of thyroid volume and the prevalence of goitre . In this prospect i ve study of a m and atory iodization programme , we aim ed to evaluate serum thyroglobulin ( Tg ) as a marker of iodine status in the population . METHODS Two identical cross-sectional studies were performed before ( 1997 - 1998 , n=4649 ) and after ( 2004 - 2005 , n=3570 ) the initiation of the Danish iodization programme in two areas with mild and moderate iodine deficiency . Serum Tg was measured from blood sample s. Thyroid volume was measured by ultrasonography . RESULTS Before iodization , the median serum Tg was considerably higher in moderate than in mild iodine deficiency . Iodization led to a lower serum Tg in all examined age groups . The marked pre-iodization difference in Tg level between the regions was eliminated . The prevalence of Tg above the suggested reference limit ( 40 microg/l ) decreased from 11.3 to 3.7 % ( P efficacy of Tg than of thyroid volume to show a difference between pre- and post-iodization values . CONCLUSION We found serum Tg to be a suitable marker of iodine nutrition status in the population . The results may suggest that the Danish iodization programme has led to a sufficient iodine intake , even if the median UI excretion is still marginally low according to WHO criteria", "OBJECTIVE Selenium is present in the active site of proteins important for thyroid hormone synthesis and metabolism . The objective of this study is to investigate the effect of selenium supplementation in different doses on thyroid function , under conditions of suboptimal dietary selenium intake . DESIGN The Danish PREvention of Cancer by Intervention with SElenium pilot study ( DK-PRECISE ) is a r and omized , double-blinded , placebo-controlled trial . A total of 491 males and females aged 60 - 74 years were r and omized to 100 μg ( n=124 ) , 200 μg ( n=122 ) , or 300 μg ( n=119 ) selenium-enriched yeast or matching yeast-based placebo tablets ( n=126 ) . A total of 361 participants , equally distributed across treatment groups , completed the 5-year intervention period . METHODS Plasma sample s were analyzed for selenium and serum sample s for TSH , free triiodothyronine ( FT3 ) , and free thyroxine ( FT4 ) at baseline , and after 6 months , and 5 years of supplementation . RESULTS Plasma selenium concentrations increased significantly and dose-dependently in treatment groups receiving selenium ( P ) . Serum TSH and FT4 concentrations decreased significantly and dose-dependently by 0.066 mIU/l ( P=0.010 ) and 0.11 pmol/l ( P=0.015 ) , respectively , per 100 μg/day increase , with insignificant differences between 6 months and 5 years . No significant effects were found for FT3 and FT3:FT4 ratio . CONCLUSIONS In euthyroid subjects , selenium supplementation minutely and dose-dependently affects thyroid function , when compared with placebo , by decreasing serum TSH and FT4 concentrations . Based on these findings , selenium supplementation is not warranted under conditions of marginal selenium deficiency . However , a role for selenium supplementation in the treatment of autoimmune thyroid diseases is still unresolved", "The New Zeal and environment is low in selenium and iodine , and is therefore ideally suited for the study of these anionic trace elements . The aim of this study was to determine urinary excretion of selenium and iodine during pregnancy and postpartum as part of an investigation of the influence of pregnancy and lactation on selenium metabolism in women of low selenium status . In a double-blind placebo-controlled study , 35 women in the earliest stages of pregnancy and 17 non-pregnant women were recruited in Dunedin , New Zeal and . Eighteen pregnant women received 50 microg selenium as L-selenomethionine , while the others received a placebo daily during pregnancy and 12 months postpartum . The non-pregnant women received the supplement , serving as a positive control . Blood sample s and twenty-four hour urine sample s were collected monthly during pregnancy and at 3 , 6 , and 12 months postpartum for analysis of selenium and iodine . Selenium content in plasma and urinary excretion of selenium fell during pregnancy ; however , total excretion of selenium was greater during pregnancy than postpartum . Urinary iodine excretion was much lower than reported previously in New Zeal and . Due to large intra- and inter-subject variability , no trends in iodide excretion were observed . Factors which influence urinary excretion of selenium include dietary intake , but more closely , plasma concentrations of selenium ( which is probably related to total selenium pool ) , creatinine excretion and therefore lean body mass , and glomerular filtration rate . The exact mechanism and sequence of events remains unclear and future studies incorporating new speciation techniques are necessary", "OBJECTIVE Adequate iodine and Fe intakes are imperative during pregnancy to prevent fetal defects , but such data are not available in the Democratic Republic of Congo . We aim ed to assess iodine and Fe status in pregnant women from Lubumbashi . DESIGN Cross-sectional study . We measured urinary iodine concentration ( UIC ) in r and om urine sample s using a modified S and ell – Kolthoff digestion method ; the WHO reference medians were used to classify iodine intake as deficient , adequate , more than adequate or excessive . Serum ferritin concentrations were measured by immunoenzymatic assay and considered insufficient when , 12 ng/ml . SETTING Maternity units from rural , semi-urban and urban areas of Lubumbashi , Democratic Republic of Congo . SUBJECTS Two hundred and twenty-five r and omly selected pregnant women attending prenatal consultation , seventy-five postpartum women and seventy-five non-pregnant women as controls . RESULTS Overall median UIC in pregnant women was 138 ( interquartile range : 105–172 ) mg/l , indicating iodine deficiency , whereas postpartum and nonpregnant women had adequate iodine intake : median UIC5144mg/l and 204mg/l , respectively . Median UIC values were lower in late pregnancy than in early pregnancy : in the first , second and third trimester respectively 255mg/l , 70mg/l and 88mg/l in the rural area ; 306mg/l , 166mg/l and 68mg/l in the semi-urban area ; and 203mg/l , 174mg/l and 99mg/l in the urban area . Fe was insufficient in 39 % of pregnant women compared with 21 % of non-pregnant and postpartum women . In the third trimester , deficiencies in both iodine and Fe were high : 40 % , 12 % and 18 % in the rural , semi-urban and urban areas , respectively . CONCLUSIONS Our data suggest that pregnant women are at risk of iodine and Fe deficiencies in Lubumbashi . Country policies fighting against iodine and Fe deficiencies during pregnancy should be reinforced", "BACKGROUND In many developing countries , children are at high risk for both goiter and anemia . In areas of subsistence farming in rural Africa , salt is one of the few regularly purchased food items and could be a good fortification vehicle for iodine and iron , provided that a stable yet bioavailable iron fortificant is used . OBJECTIVE We tested the efficacy of salt dual-fortified with iodine and micronized ferric pyrophosphate for reducing the prevalence of iodine and iron deficiencies in children . DESIGN In rural northern Morocco , we fortified local salt with 25 microg I ( as potassium io date ) /g salt and 2 mg Fe ( as micronized ferric pyrophosphate ; mean particle size = 2.5 microm)/g salt . After storage and acceptability trials , we compared the efficacy of the dual-fortified salt ( DFS ) with that of iodized salt in a 10-mo , r and omized , double-blind trial in iodine-deficient 6 - 15-y-old children ( n = 158 ) with a high prevalence of anemia . RESULTS After storage for 6 mo , there were no significant differences in iodine content or color lightness between the DFS and iodized salt . During the efficacy trial , the DFS provided approximately 18 mg Fe/d ; iron absorption was estimated to be approximately 2 % . After 10 mo of treatment in the DFS group , mean hemoglobin increased by 16 g/L ( P iron status and body iron stores increased significantly ( P iron deficiency anemia decreased from 30 % at baseline to 5 % ( P urinary iodine ( P thyroid volume ( P < 0.01 ) improved significantly from baseline . CONCLUSION A DFS containing iodine and micronized ferric pyrophosphate can be an effective fortification strategy in rural Africa", "BACKGROUND Vitamin D is an immunomodulator and may affect autoimmune thyroid diseases . Vitamin D has also been shown to influence thyrocytes directly by attenuating thyrotropin (TSH)-stimulated iodide uptake and cell growth . However , it is unclear how vitamin D status is related to TSH at the population level . The goal of the present study was to investigate the relationship between vitamin D status and TSH levels according to thyroid autoantibodies in a population -based health survey in Thail and . METHODS A total of 2582 adults , aged 15 - 98 years , were r and omly selected according to the geographical region from the Thail and 4th National Health Examination Survey sample . By study design , the sexes were equally represented . Serum levels of 25-hydroxyvitamin D [ 25(OH)D ] , TSH , the thyroid peroxidase antibody ( TPOAb ) , and the thyroglobulin antibody ( TgAb ) were measured in all subjects . RESULTS The mean age was 55.0±0.4 ( SE ) years . In subjects positive for serum TgAb , serum TSH levels were higher , whereas total serum 25(OH)D levels were lower . In addition , the prevalence of vitamin D insufficiency in TgAb-positive subjects was significantly higher than that observed in TPOAb- and TgAb-negative subjects , whether based on cutoff values of 20 or 30 ng/mL : 8.3 % vs. 5.6 % , p respectively . However , vitamin D status was not associated with positive TPOAb and /or TgAb after controlling for sex and age . To explore the probable interaction between vitamin D status and age on serum TSH , analyses were performed according to age tertiles ; it was found that higher 25(OH)D levels were independently associated with lower TSH , but only in subjects in the lowest age tertile . CONCLUSIONS This population -based study showed that high vitamin D status in younger individuals is associated with low circulating TSH", "The aim of this study was to determine whether iron supplementation in iron-deficient adolescent girls would improve thyroid function . A double-blind clinical trial was performed in a region in southern I.R. Iran . A total of 103 iron deficient participants were chosen . In all , 94 participants successfully completed this study . Participants were r and omly assigned to one of two groups and treated with a 300 mg ferrous sulfate 5 times/week ( n = 47 ) and placebo 5 times/week ( n = 47 ) for 12 weeks . Blood sample s were collected and assayed for hemoglobin , hematocrit , serum ferritin , iron , total iron binding capacity ( TIBC ) , Thyroid stimulating hormone ( TSH ) , total thyroxine ( TT4 ) , total triiodothyronine ( TT3 ) , free thyroid hormones ( FT4 and FT3 ) , triiodothyronine resin uptake ( T3RU ) , reverse triiodothyronine ( rT3 ) , selenium and albumin concentrations . Statistical analysis was performed with parametric and non-parametric methods as appropriate . Data analysis revealed a significant increase in TT4 , TT3 , T3RU and a significant decrease in rT3 concentration in comparison to initial values in iron treated group ( 12 % , p TT4 , TT3 , T3RU and rT3 concentrations ( 9.9 vs 8.4 microg dL(-1 ) , 145.2 vs 130.4 microg dL(-1 ) , 32.5 vs 28.4 % and 23 vs 41 microg dL(-1 ) , respectively , all p Alterations in FT3 and TSH concentration were not significant , but concentration of FT4 revealed a significant difference between the beginning and the end of the study in iron treated group ( 10.3 vs 11.4 , p thyroid function in iron-deficient adolescent girls", "OBJECTIVE Iodine deficiency has re-emerged in New Zeal and , while selenium status has improved . The aim of this study was to investigate the effects of excess iodine intake as io date on thyroid and selenium status . METHODS In a r and omized controlled trial on older people ( mean±s.d . 73±4.8 years ; n=143 ) , two groups received > 50 mg iodine as io date /day for 8 weeks because of supplement formulation error , either with 100 μg selenium ( Se+highI ) or without selenium ( highI ) . Four other groups received 80 μg iodine as io date /day with selenium ( Se+lowI ) or without selenium ( lowI ) , selenium alone ( Se+ ) , or placebo . Thyroid hormones , selenium status , and median urinary iodine concentration ( MUIC ) were compared at weeks 0 , 8 , and 4 weeks post-supplementation . RESULTS MUIC increased nine- and six-fold in Se+highI and highI groups , decreasing to baseline by week 12 . Plasma selenium increased in selenium-supplemented groups ( P increase in whole blood glutathione peroxidase ( WBGPx ) in the Se+highI group was smaller than Se+ ( P=0.020 ) and Se+lowI ( P=0.007 ) groups . The decrease in WBGPX in the highI group was greater than other non-selenium-supplemented groups , but differences were not significant . Ten of 43 participants exposed to excess io date showed elevated TSH ( hypothyroidism ) at week 8 . In all but two , TSH had returned to normal by week 12 . In three participants , TSH decreased to reduced WBGPx activity and result ed in smaller increases in WBGPx after selenium supplementation", "BACKGROUND The New Zeal and population has both marginal selenium status and mild iodine deficiency . Adequate intakes of iodine and selenium are required for optimal thyroid function . OBJECTIVE The aim of the study was to determine whether low selenium and iodine status compromises thyroid function in an older New Zeal and population . DESIGN We investigated the effects of selenium and iodine supplementation in a double-blind , r and omized , placebo-controlled trial in 100 Dunedin volunteers aged 60 - 80 y. Participants received 100 microg Se/d as l-selenomethionine , 80 microg I , 100 microg Se + 80 microg I , or placebo for 3 mo . Thyroid-stimulating hormone ( TSH ) , free triiodothyronine ( T(3 ) ) , free thyroxine ( T(4 ) ) , thyroglobulin , plasma selenium , whole-blood glutathione peroxidase ( GPx ) activity , and urinary iodine concentrations ( UICs ) were measured . RESULTS Plasma selenium ( P whole-blood GPx activity ( P selenium and selenium plus iodine groups in comparison with the placebo group . Median UIC at baseline was 48 microg/L ( interquartile range : 31 - 79 microg/L ) , which is indicative of moderate iodine deficiency . UIC increased in the iodine and selenium plus iodine groups and was significant only for the iodine group ( P = 0.0014 ) . Thyroglobulin concentration decreased by 24 % and 13 % of baseline in the iodine and selenium plus iodine groups in comparison with the placebo group ( P = 0.009 and P = 0.108 , respectively ) . No significant treatment effects were found for TSH , free T(3 ) , free T(4 ) , or ratio of T(3 ) to T(4 ) . CONCLUSIONS Additional selenium improved GPx activity but not the thyroid hormone status of older New Zeal and ers . Iodine supplementation alleviated the moderate iodine deficiency and reduced elevated thyroglobulin concentrations . No synergistic action of selenium and iodine was observed . The trial was registered at www.anzctr.org.au/registry/ as ACTRN012605000368639", "Objective : To investigate whether iron supplementation can improve thyroid hormone function in iron-deficient adolescent girls . Design : A double-blind r and omized intervention study . Setting : The study was performed from 2002 through 2003 in the Islamic Republic of Iran . Subjects:103 iron-deficient non-anaemic girls who fulfilled all inclusion criteria were included , and 94 subjects successfully completed the study . Interventions : Patients were r and omly assigned to one of four groups and treated with a single oral dose of 190 mg iodine plus 300 mg ferrous sulphate 5 times/week ( n=24 ) , 300 mg ferrous sulphate 5 times/week ( n=23 ) , a single oral dose of 190 mg iodine ( n=25 ) , or a placebo ( n=22 ) for 12 weeks . Results : All groups were comparable at baseline . After the intervention , there was a significant increase in ferritin and transferrin saturation in the iron+iodine group ( 17.6 vs 8.7 μg/dl , and 18.8 vs 7.2 % , respectively , P . Urinary iodine doubled in the iron+iodine group and in the iodine group ( P both ) . Thyroid indices tT4 , tT3 and T3RU increased and reverse RT3 decreased in the iron+iodine group ( 10 vs 8.9 μg/dl , P thyroid hormones . Sponsorship : This study was supported by the Dean of Research Affairs of the Tehran University of Medical Sciences", "Iodine is an essential element with unique role in organism : it is indispensable component of thyroid hormones . After binding with specific nuclear receptor , T3/T4 induce transcription of genetic code via mRNA and regulate proteo synthesis in most tissues . Thyroid hormones regulate rate of metabolic processes and consequently development of organism . Czech Republic was in past typical region with moderate to severe iodine deficiency . Therefore epidemiological survey was started in r and omly selected sample s of peoples . Thereafter a complex program of improving iodine supply was realized . Prompt effects of this changes were recorded , namely increase of ioduria and decrease of thyroid volume . Essential trace element selenium has a fundamental importance to the cell and body metabolism regulation by thyroid hormones . Activities of selenoenzymes deiodinases lead to the activation of prohormone T4 to active hormone T3 and the inactivation of T3 and of T4 , as well . There is unfortunately moderate to mild Se deficit in the CR . Average serum Se concentrations for the population s from 6 to 65 years are in the regions of the CR between 42 and 62 micrograms/l and urine Se values are between 8 and 15 micrograms/l . We have found statistically significant correlations among indexes of selenium status and indexes of thyroid hormone metabolism and function . Especially dangerous are concomitant deficiencies of both key elements for thyroid hormone metabolism -- I and Se -- from the point of thyroid hormone regulative functions", "1 . Iodothyronine 5'-deiodinase , which is mainly responsible for peripheral triiodothyronine ( T3 ) production , has recently been demonstrated to be a selenium-containing enzyme . In the elderly , reduced peripheral conversion of thyroxine ( T4 ) to T3 and overt hypothyroidism are frequently observed . 2 . We measured serum selenium and erythrocyte glutathione peroxidase ( as indices of selenium status ) , thyroid hormones and thyroid-stimulating hormone in 109 healthy euthyroid subjects ( 52 women , 57 men ) , carefully selected to exclude abnormally low thyroid hormone levels induced by acute or chronic diseases or calorie restriction . The subjects were subdivided into three age groups . To avoid conditions of under-nutrition or malnutrition , dietary records were obtained for a sample of 24 subjects , r and omly selected and representative of the whole population for age and sex . 3 . In order to properly assess the influence of selenium status on iodothyronine 5'-deiodinase type I activity , a double-blind placebo-controlled trial was also carried out on 36 elderly subjects , resident at a privately owned nursing home . 4 . In the free-living population , a progressive reduction of the T3/T4 ratio ( due to increased T4 levels ) and of selenium and erythrocyte glutathione peroxidase activity was observed with advancing age . A highly significant linear correlation between T4 , T3/T4 and selenium was observed in the population as a whole ( for T4 , R = -0.312 , P selenium indices and a decrease in the T4 level in selenium-treated subjects ; serum selenium , erythrocyte glutathione peroxidase activity and thyroid hormones did not change in placebo-treated subjects . 6 . We concluded that selenium status influences thyroid hormones in the elderly , mainly modulating T4 levels", "BACKGROUND Iron may be only one of many nutritional factors that influence thyroid hormone metabolism in iodine-deficient areas . OBJECTIVE To evaluate the effect of iron status on thyroid hormone profile in adolescents living in a mild iodine-deficient area in Turkey . SUBJECTS Three hundred and thirty school-aged children with mean age 14 years were examined . METHODS Free triiodothyronine , free tetraiodothyronine and thyrotropin levels were analyzed by chemiluminescent enzyme immunoassay . Hemoglobin and mean corpuscular volume were measured with a Hemocounter . Iron and total iron binding capacity concentration were determined by colorimetric photometric methods . Ferritin level was determined by immunoturbidimetry . RESULTS Thyroid hormone levels of the children with anemia were not significantly different compared to children without anemia . No significant correlation was found between thyroid hormones and iron status . CONCLUSION The thyroid hormone profile was not significantly affected in this area . This survey showed no correlation between iron status and thyroid hormone levels", "In order to explore the associations between trace elements in dietary intake and the other three biological media ( blood , urine , or feces ) and inter-element interactions among the latter , we simultaneously collected 72-h diet duplicates , whole blood , and 72-h urine and feces from 120 free-living healthy males in China . Correlations among the toxic ( cadmium [ Cd ] , lead [ Pb ] ) , and nutritionally essential ( zinc [ Zn ] , copper [ Cu ] , iron [ Fe ] , manganese [ Mn ] , selenium [ Se ] , iodine [ I ] ) elements were evaluated using Spearman rank correlation analysis based on analytical data determined by inductively coupled plasma-mass spectrometry . Dietary Cd intakes were highly correlated with the fecal Cd and blood Cd levels . Inverse correlations were found for Fe – Cd and Fe – Pb in both diet versus blood and diet versus feces . Cd – Zn and Cd – Se were significantly directly correlated in the urine and feces . Cd – Se and Pb – Se were negatively correlated in blood . In addition , there existed an extremely significant association between urinary Se and urinary I. Moreover , the other two highly direct correlations were found for Se – Fe and for I – Fe in urine . Improved knowledge regarding their mutual associations is considered to be of fundamental importance to underst and more the complex interrelationships in trace element metabolism" ]	41188fba-06ff-11f0-808a-c43d1ab1c353
Osteoporosis ( OP ) is a major public health concern , but still OP care does not meet guidelines . Interventions have been developed to improve appropriate OP management . The objective of the present study was to systematic ally review the current literature to ascertain the efficacy of interventions to improve OP care and characterize interventions taking into account elements related to their potential cost and feasibility . Studies published from 2003 to 2018 were retrieved from PubMed / MEDLINE , Science Direct , Web of Science , Cochrane , and Wiley Online Library data bases . Screening of references and quality assessment were independently performed by two review ers . We classified interventions into three types according to the target of the intervention : health system ( structural interventions ) , healthcare professional ( HCP ) , and patient . Meta- analysis was performed by type of intervention and their effect on two outcomes : prescription of BMD measurement and prescription of OP therapy . A total of 4268 records were screened ; 32 studies were included in the qualitative analysis and 29 studies in the quantitative analysis . Structural interventions strongly and significantly improved prescription of BMD measurement ( OR = 9.99 , 95 % CI 2.05 ; 48.59 ) and treatment prescription ( OR = 3.82 , 95 % CI 2.16 ; 6.75 ) . The impact of HCP-centered interventions on BMD measurement prescription did not reach statistical significance ( OR = 2.19 , 95 % CI 0.84 ; 5.73 ) but significantly improved treatment prescription ( OR = 3.82 , 95 % CI 2.16 ; 6.75 ) . Interventions involving patients significantly improved the prescription of BMD measurement ( OR = 2.16 , 95 % CI 1.62 ; 2.89 ) and treatment prescription ( OR = 1.70 , 95 % CI 1.35 ; 2.14 ) . Interventions to improve OP management had a significant positive impact on prescription of BMD measurement but a more limited impact on treatment prescription	[ "Background : Postfracture care is suboptimal , and strategies to address this major gap in care are necessary . We investigated whether notifications sent by mail to physicians and patients would lead to improved postfracture care . Methods : We conducted a r and omized controlled trial ( Clinical Trials.gov identifier NCT00594789 ) in the province of Manitoba , Canada , from June 2008 to May 2010 . Using medical cl aims data , we identified 4264 men and women age 50 years or older who recently reported major fractures , and who had not undergone recent bone mineral density testing or treatment for osteoporosis . Participants were r and omized to three groups : group 1 received usual care ( n = 1480 ) , patients in group 2 had mailed notification of the fracture sent to their primary care physicians ( n = 1363 ) , and group 3 had notifications sent to both physicians and patients ( n = 1421 ) . Bone mineral density testing and the start of pharmacologic treatment for osteoporosis within the following 12 months were documented . Results : Among participants in group 1 ( usual care ) , 15.8 % of women and 7.6 % of men underwent testing for bone mineral density or started pharmacologic treatment for osteoporosis . Outcome measures improved among participants in group 2 ( 30.3 % of women and 19.0 % of men , both p end point of bone mineral density testing or pharmacologic treatment was 14.9 % ( 16.4 % among women , 11.8 % among men ) . The number needed to notify to change patient care was 7 ( 6 for women , 6 for men ) . The adjusted odds ratio ( OR ) to change patient care in group 2 was 2.45 ( 95 % confidence interval [ CI ] 2.01–2.98 ) ; for group 3 the OR was 2.82 ( 95 % CI 2.33–3.43 ) . Interpretation : This notification system provides a relatively simple way to enhance post-fracture care", "BACKGROUND AND PURPOSE An active strategy was developed for the implementation of the clinical guidelines on physical therapy for patients with low back pain . The effect of this strategy on patients ' physical functioning , coping strategy , and beliefs regarding their low back pain was studied . SUBJECTS One hundred thirteen primary care physical therapists treated a total of 500 patients . METHODS The physical therapists were r and omly assigned to 1 of 2 groups . The control group received the guidelines by mail ( st and ard passive method of dissemination ) . The intervention group , in contrast , received an additional active training strategy consisting of 2 sessions with education , group discussion , role playing , feedback , and reminders . Patients with low back pain , treated by the participating therapists , completed question naires on physical functioning , pain , sick leave , coping , and beliefs . RESULTS Physical functioning and pain in the 2 groups improved substantially in the first 12 weeks . Multilevel longitudinal analysis showed no differences between the 2 groups on any outcome measure during follow-up . DISCUSSION AND CONCLUSION The authors found no additional benefit to applying an active strategy to implement the physical therapy guidelines for patients with low back pain . Active implementation strategies are not recommended if patient outcomes are to be improved", "Background A care gap exists between the health care needs of older persons with fragility fractures and the therapeutic answers they receive . The Fracture Prevention Service ( FPS ) , a tailored in-hospital model of care , may effectively bridge the osteoporosis care gap for hip-fractured older persons . The purpose of this study was to evaluate the efficacy of the FPS in targeting persons at high risk of future fracture and to improve their adherence to treatment . Methods This was a prospect i ve observational study conducted in a teaching hospital with traumatology and geriatric units , and had a pre-intervention and post-intervention phase . The records of 172 participants were evaluated in the pre-intervention phase , while data from 210 participants were gathered in the post-intervention phase . All participants underwent telephone follow-up at 12 months after hospital discharge . The participants were patients aged ≥65 years admitted to the orthopedic acute ward who underwent surgical repair of a proximal femoral fracture . A multidisciplinary integrated model of care was established . Dedicated pathways were implemented in clinical practice to optimize the identification of high-risk persons , improve their evaluation through bone mineral density testing and blood examinations , and initiate an appropriate treatment for secondary prevention of falls and fragility fractures . Results Compared with the pre-intervention phase , more hip-fractured persons received bone mineral density testing ( 47.62 % versus 14.53 % , P specific pharmacological treatments ( 48.51 % versus 17.16 % , P an appointment for evaluation at a fall and fracture clinic ( 52.48 % versus 2.37 % , P with recommendations for secondary fracture prevention at discharge ( P with 1-year adherence to pharmacological treatment ( P The FPS is an effective multidisciplinary integrated model of care to optimize identification of older persons at highest risk for fragility fracture , to improve their clinical management , and to increase adherence to prescriptions", "BACKGROUND Despite effective assessment methods and medications targeting osteoporosis and related fractures , screening for fracture risk is not currently advocated in the UK . We tested whether a community-based screening intervention could reduce fractures in older women . METHODS We did a two-arm r and omised controlled trial in women aged 70 - 85 years to compare a screening programme using the Fracture Risk Assessment Tool ( FRAX ) with usual management . Women were recruited from 100 general practitioner ( GP ) practice s in seven regions of the UK : Birmingham , Bristol , Manchester , Norwich , Sheffield , Southampton , and York . We excluded women who were currently on prescription anti-osteoporotic drugs and any individuals deemed to be unsuitable to enter a research study ( eg , known dementia , terminally ill , or recently bereaved ) . The primary outcome was the proportion of individuals who had one or more osteoporosis-related fractures over a 5-year period . In the screening group , treatment was recommended in women identified to be at high risk of hip fracture , according to the FRAX 10-year hip fracture probability . Prespecified secondary outcomes were the proportions of participants who had at least one hip fracture , any clinical fracture , or mortality ; and the effect of screening on anxiety and health-related quality of life . This trial is registered with the International St and ard R and omised Controlled Trial registry , number IS RCT N 55814835 . FINDINGS 12 483 eligible women were identified and participated in the trial , and 6233 women r and omly assigned to the screening group between April 15 , 2008 , and July 2 , 2009 . Treatment was recommended in 898 ( 14 % ) of 6233 women . Use of osteoporosis medication was higher at the end of year 1 in the screening group compared with controls ( 15 % vs 4 % ) , with uptake particularly high ( 78 % at 6 months ) in the screening high-risk subgroup . Screening did not reduce the primary outcome of incidence of all osteoporosis-related fractures ( hazard ratio [ HR ] 0·94 , 95 % CI 0·85 - 1·03 , p=0·178 ) , nor the overall incidence of all clinical fractures ( 0·94 , 0·86 - 1·03 , p=0·183 ) , but screening reduced the incidence of hip fractures ( 0·72 , 0·59 - 0·89 , p=0·002 ) . There was no evidence of differences in mortality , anxiety levels , or quality of life . INTERPRETATION Systematic , community-based screening programme of fracture risk in older women in the UK is feasible , and could be effective in reducing hip fractures . FUNDING Arthritis Research UK and Medical Research Council", "ABBREVIATIONS AACE = American Association of Clinical Endocrinologists AFF = atypical femur fracture ASBMR = American Society for Bone and Mineral Research BEL = best evidence level BMD = bone mineral density BTM = bone turnover marker CBC = complete blood count CI = confidence interval DXA = dual-energy X-ray absorptiometry EL = evidence level FDA = U.S. Food and Drug Administration FLEX = Fracture Intervention Trial ( FIT ) Long-term Extension FRAX ® = Fracture Risk Assessment Tool GFR = glomerular filtration rate GI = gastrointestinal HORIZON = Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly IOF = International Osteoporosis Foundation ISCD = International Society for Clinical Densitometry IU = international units IV = intravenous LSC = least significant change NBHA = National Bone Health Alliance NOF = National Osteoporosis Foundation 25(OH)D = 25-hydroxy vitamin D ONJ = osteonecrosis of the jaw PINP = serum carboxy-terminal propeptide of type I collagen PTH = parathyroid hormone R = recommendation RANK = receptor activator of nuclear factor kappa-B RANKL = receptor activator of nuclear factor kappa-B lig and RCT = r and omized controlled trial RR = relative risk S-CTX = serum C-terminal telopeptide SQ = subcutaneous VFA = vertebral fracture assessment WHO = World Health Organization", "Background Osteoporosis affects over 200 million people worldwide at a high cost to healthcare systems , yet gaps in management still exist . In response , we developed a multi-component osteoporosis knowledge translation ( Op-KT ) tool involving a patient-initiated risk assessment question naire ( RAQ ) , which generates individualized best practice recommendations for physicians and customized education for patients at the point of care . The objective of this study was to evaluate the effectiveness of the Op-KT tool for appropriate disease management by physicians . Methods The Op-KT tool was evaluated using an interrupted time series design . This involved multiple assessment s of the outcomes 12 months before ( baseline ) and 12 months after tool implementation ( 52 data points in total ) . Inclusion criteria were family physicians and their patients at risk for osteoporosis ( women aged ≥50 years , men aged ≥65 years ) . Primary outcomes were the initiation of appropriate osteoporosis screening and treatment . Analyses included segmented linear regression modeling and analysis of variance . Results The Op-KT tool was implemented in three family practice s in Ontario , Canada representing 5 family physicians with 2840 age eligible patients ( mean age 67 years ; 76 % women ) . Time series regression models showed an overall increase from baseline in the initiation of screening ( 3.4 % ; P osteoporosis medications ( 0.5 % ; P = 0.006 ) , and calcium or vitamin D ( 1.2 % ; P = 0.001 ) . Improvements were also observed at site level for all the three sites considered , but these results varied across the sites . Of 351 patients who completed the RAQ unprompted ( mean age 64 years , 77 % women ) , the mean time for completing the RAQ was 3.43 minutes , and 56 % had any disease management addressed by their physician . Study limitations included the inherent susceptibility of our design compared with a r and omized trial . Conclusions The multicomponent Op-KT tool significantly increased osteoporosis investigations in three family practice s , and highlights its potential to facilitate patient self-management . Next steps include wider implementation and evaluation of the tool in primary care", "Background Despite recommendations , osteoporosis screening rates among women aged 65 years and older remain low . We present results from a clustered , r and omized trial evaluating patient mailed reminders , alone and in combination with physician prompts , to improve osteoporosis screening and treatment . Methods Primary care clinics ( n = 15 ) were r and omized to usual care , mailed reminders alone , or mailed reminders with physician prompts . Study patients were females aged 65–89 years ( N = 10,354 ) . Using automated clinical and pharmacy data , information was collected on bone mineral density testing , pharmacy dispensings , and other patient characteristics . Unadjusted/adjusted differences in testing and treatment were assessed using generalized estimating equation approaches . Results Osteoporosis screening rates were 10.8 % in usual care , 24.1 % in mailed reminder , and 28.9 % in mailed reminder with physician prompt . Results adjusted for differences at baseline indicated that mailed reminders significantly improved testing rates compared to usual care , and that the addition of prompts further improved testing . This effect increased with patient age . Treatment rates were 5.2 % in usual care , 8.4 % in mailed reminders , and 9.1 % in mailed reminders with prompt . No significant differences were found in treatment rates between those receiving mailed reminders alone or in combination with physician prompts . However , women receiving usual care were significantly less likely to be treated . Conclusions The use of mailed reminders , either alone or with physician prompts , can significantly improve osteoporosis screening and treatment rates among insured primary care patients ( Clinical Trials.gov number NCT00139425 )", "Background Despite accurate diagnostic tests and effective therapies , the management of osteoporosis has been observed to be suboptimal in many setting s. We tested the effectiveness of an intervention to improve care in patients at-risk of osteoporosis . Design R and omized controlled trial . Participants Primary care physicians and their patients at-risk of osteoporosis , including women 65 years and over , men and women 45 and over with a prior fracture , and men and women 45 and over who recently used ≥90 days of oral glucocorticoids . InterventionA multifaceted program of education and reminders delivered to primary care physicians as well as mailings and automated telephone calls to patients . Outcome : Either undergoing a bone mineral density ( BMD ) testing or filling a prescription for a bone-active medication during the 10 months of follow-up . Results After the intervention , 144 ( 14 % ) patients in the intervention group and 97 ( 10 % ) patients in the control group received either a BMD test or filled a prescription for an osteoporosis medication . This represents a 4 % absolute increase and a 45 % relative increase ( 95 % confidence interval 9–93 % , p = 0.01 ) in osteoporosis management between the intervention and control groups . No differences between groups were observed in the incidence of fracture . Conclusion An intervention targeting primary care physicians and their at-risk patients increased the frequency of BMD testing and /or filling prescriptions for osteoporosis medications . However , the absolute percentage of at-risk patients receiving osteoporosis management remained low", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "UNLABELLED We conducted a r and omized controlled trial within the setting of a large drug benefit plan for Medicare beneficiaries . Primary care physicians and their patients were r and omized to usual care , patient intervention only , physician intervention only , or both interventions . There was no difference in the probability of the primary composite endpoint ( BMD test or osteoporosis medication ) or in either of its components comparing the combined intervention group with usual care ( risk ratio = 1.04 ; 95 % CI , 0.85 - 1.26 ) . INTRODUCTION Fractures from osteoporosis are associated with substantial morbidity , mortality , and cost . However , only a minority of at-risk older adults receives screening and /or treatment for this condition . We evaluated the effect of educational interventions for osteoporosis targeting at-risk patients , primary care physicians , or both . MATERIAL S AND METHODS We conducted a r and omized controlled trial within the setting of a large drug benefit plan for Medicare beneficiaries . Primary care physicians and their patients were r and omized to usual care , patient intervention only , physician intervention only , or both interventions . The at-risk patients were women > or=65 yr of age , men and women > or=65 yr of age with a prior fracture , and men and women > or=65 yr of age who used oral glucocorticoids . The primary outcome studied was a composite of either undergoing a BMD test or initiating a medication used for osteoporosis . The secondary outcome was a hip , humerus , spine , or wrist fracture . RESULTS We r and omized 828 primary care physicians and their 13,455 eligible at-risk patients into four study arms . Physician and patient characteristics were very similar across all four groups . Across all four groups , the rate of the composite outcome was 10.3 per 100 person-years and did not differ between the usual care and the combined intervention groups ( p = 0.5 ) . In adjusted Cox proportional hazards models , there was no difference in the probability of the primary composite endpoint comparing the combined intervention group with usual care ( risk ratio = 1.04 ; 95 % CI , 0.85 - 1.26 ) . There was also no difference in either of the components of the composite endpoint . The probability of fracture during follow-up was 4.2 per 100 person-years and did not differ by treatment assignment ( p = 0.9 ) . CONCLUSIONS In this trial , a relatively brief program of patient and /or physician education did not work to improve the management of osteoporosis . More intensive efforts should be considered for future quality improvement programs for osteoporosis", "Summary The aim of this study was to determine whether feedback by pharmacists to prescribers of patients eligible for glucocorticoid-induced osteoporosis prophylaxis would stimulate the prescribing of osteoporosis prophylaxis . The intervention did not significantly increase the prescribing of bisphosphonates in the total study population , but a significant increase was seen in men and in the elderly . However , the proportion of bisphosphonate-treated patients remained low . Introduction The aim of this study was to determine whether feedback by pharmacists to prescribers of patients eligible for glucocorticoid-induced osteoporosis prophylaxis ( GIOP ) would stimulate the implementation of the Dutch GIOP guideline . Methods This r and omised controlled trial included 695 patients who were dispensed ≥675 mg prednisone equivalents without a concomitant bisphosphonate prescription within 6 months before baseline . Pharmacists were asked to contact the physicians of GIOP-eligible patients in the intervention group to suggest osteoporosis prophylaxis . The primary endpoint was a bisphosphonate prescription . Secondary endpoints were a prescription of calcium supplements , vitamin D or any prophylactic osteoporosis drug ( bisphosphonate , calcium supplements , vitamin D ) . Results The group assigned to the intervention was slightly younger than the control group ( 68.7 ± 15.4 vs. 65.9 ± 16.9 years , p = 0.02 ) and used hydrocortisone more often ( 7.0 % vs. 3.1 % , p = 0.02 ) . Within 6 months , the intervention did not significantly increase the prescribing of bisphosphonates ( 11.4 % after intervention vs. 8.0 % for controls ; hazard ratio [ HR ] 1.47 , 95 % confidence interval [ CI ] 0.91–2.39 ) . However , subgroup analyses showed a significant increase for the primary endpoint in men ( 12.8 % vs. 5.1 % , HR 2.53 , 95 % CI 1.11–5.74 ) and patients ≥70 years ( 13.4 % vs. 4.9 % , HR 2.88 , 95 % CI 1.33–6.23 ) . The prescribing of calcium and vitamin D was not significantly altered . Conclusion This study showed that active identification of patients eligible for GIOP by pharmacists did not significantly increase the prescribing of bisphosphonates in the total study population , but there was an increase in men and the elderly . However , the proportion of GIOP-treated patients remained low", "Objective . To evaluate 2 incremental levels of intervention design ed to increase initiation of osteoporosis treatment by primary care physicians ( PCP ) following fragility fractures ( FF ) . Methods . Women and men over age 50 years were screened for incident FF in fracture clinics , and eligible out patients were r and omly assigned to st and ard care ( SC ) or to either minimal ( MIN ) or intensive ( INT ) interventions . The MIN and INT interventions were intended to educate and motivate both patients and PCP , but differed in their frequency of contact and information content . Delivery of osteoporosis medication was confirmed with pharmacists . Treatment rates were analyzed using an intention-to-treat approach . Results . At inclusion , 74.3 % of 881 out patients with FF were untreated . Followup at 12 months was completed in 92.3 % of patients . Up to 90 % of patients treated at inclusion remained treated at 12 months . Among patients who initially were untreated , 18.8 % in the SC group , 40.4 % in the MIN , and 53.2 % in the INT groups were treated at 12 months . Change in treatment rates ( adjusted for age and initial treatment ) increased significantly after both MIN and INT . Only the INT intervention significantly increased treatment rates in patients with previous fractures . Negative predictors of change in treatment status included non-major FF , age younger than 65 years , and male sex . Conclusion . Both interventions significantly increased initiation of osteoporosis treatment . Our multidisciplinary intervention builds on existing first-line structures and uses minimal specialized re sources . Iterative and systematic interventions in the context of clinical care may modify the approach of PCP to osteoporosis management after FF and narrow the care gap in the long term", "Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies", "Background : Primary care physicians often fail to diagnose low bone density . This pilot study assessed 2 interventions for their effect on bone mineral density testing . Methods : Five practice s in the Iowa Research Network were r and omized : 2 to chart reminder alone ( CR ) , 2 to chart reminder plus mailed patient education ( CR+PtEd ) , and one to usual care . A total of 204 women aged 65 years or older were recruited from within these practice s. Bayesian hierarchical analyses were used instead of traditional statistical methods to take advantage of collateral data and to adjust for differences between clinics at baseline . Results : After the intervention , the rates of completed bone mineral density testing were 45.2 % in the CR+PtEd group , 31.4 % in the chart remainder only group , and 9.7 % in the usual care practice . Bayesian analysis adjusted for patient and clinic characteristics , which made use of collateral data , gave an odds ratio of 5.47 for the effect of CR+PtEd group . The Bayesian P was .029 and the one-sided 95 % credible interval for the odds ratio was greater than 1.2 . The effect of CR+PtEd was confirmed by sensitivity analyses . Traditional hierarchical analysis adjusted for practice characteristics could not be used to estimate statistical significance because there were not enough clinics to accommo date a model that included all the important covariables . Conclusions : Specific chart reminders to physicians combined with mailed patient education substantially increased the levels of bone density testing and could potentially be used to improve osteoporosis screening in primary care . Bayesian hierarchical analysis makes it possible to assess practice -level interventions when few practice s are r and omized", "OBJECTIVE to assess whether specialist osteoporosis nurses delivering training to care home staff can reduce fractures and improve the prescription of treatments to reduce fractures versus usual care . DESIGN pragmatic cluster r and omised controlled trial ( RCT ) with r and omisation at the Primary Care Organisation ( PCO ) level . SETTING care homes ( residential , nursing and EMI ) across Engl and and Wales within PCOs . PARTICIPANTS all 300 PCOs in Engl and and Wales were invited to take part . Of these , 58 agreed to participate and gained ethical approval in time to start the study : 29 clusters were r and omised to the intervention group and 29 to the control . INTERVENTION specialist osteoporosis nurses undertaking short training sessions with care home staff emphase the importance of fracture and fall prevention and train staff on how to identify those residents at high risk of fracture . Residents ' risk of fracture and falls was reported to general practitioners ( GPs ) of patients along with treatment recommendations . OUTCOME MEASURES primary outcome measures were total fractures over the past 12 months and total hip fractures over past the 12 months . Secondary outcome measures were total home falls , number of residents sustaining a fall , number of residents prescribed bisphosphonates , number of residents prescribed calcium and vitamin D and number of residents wearing hip protectors . All outcomes were measured at the care home level . RESULTS of the 230 care homes r and omised data were collected from 209 of these containing 5,637 residents . There were no differences between the groups in the incidence rate ratios ( IRRs ) for total fractures ( IRR = 0.94 [ 0.71 , 1.26 ] P = 0.70 ) or total hip fractures ( IRR = 0.86 [ 0.63 , 1.18 ] P = 0.36 ) . No differences were found between groups for home falls or hip protector use . A significant increase in bisphosphonate prescription was seen in the intervention group over the control group ( IRR = 1.50 [ 1.00 , 2.24 ] P = 0.05 ) . Calcium and vitamin D prescription was significantly increased in the intervention group over the control group ( IRR = 1.64 [ 1.23 , 2.18 ] P<0.01 ) . CONCLUSION the intervention significantly increased the prescription of bisphosphonates and calcium/vitamin D , but was not associated with a significant effect on the rate of falls or fractures", "Introduction Osteoporosis represents a growing public health concern ; however , current rates of management are sub-optimal . The aim of our study was to assess , in a r and omized controlled trial , the effect of a mailed educational intervention on older adults ’ knowledge , attitudes , and preventive behaviors regarding osteoporosis . The setting was a large publicly funded state pharmacy benefits program . The patients were 31,715 Medicare beneficiaries from Pennsylvania who participated in a drug benefits program for low-to-moderate income elderly people . Methods All women aged over 65 years , and all men and women with a history of fracture or long-term oral use of glucocorticoid , were included . Approximately half of the participants ( intervention group ) were r and omly selected to receive three mailings aim ed at improving knowledge of osteoporosis and enhancing preventive activities , such as using calcium and vitamin D , reducing fall risks in the home , obtaining a bone mineral density ( BMD ) test , and taking medications when necessary . The other participants did not receive the intervention mailings and served as controls . We surveyed a sample of intervention and control subjects to determine the effects of the intervention on knowledge , attitudes , self-efficacy ( confidence in one ’s ability to perform specific activities ) , and behavior regarding osteoporosis prevention and treatment . Six hundred r and omly selected participants in the intervention group and an equal number in the control group were invited to participate . Results Twenty-six had died and 636 of the remaining 1,185 ( 54 % ) completed the survey . Respondents and non-respondents did not differ significantly with respect to measured sociodemographic factors . All scales had good reliability ( all Cronbach ’s alphas > 0.65 ) . Knowledge of osteoporosis was generally very good and did not differ between intervention ( mean = 65 % correct responses ) and control subjects ( mean = 67 % correct ; P=0.4 ) . Perceived susceptibility to osteoporosis was relatively high and similar across groups ( P=0.4 ) . Self-efficacy for participating in osteoporosis prevention and treatment was very strong in both the intervention ( mean = 4.3 on a 0–5 scale ) and control ( mean = 4.2 , P=0.03 ) groups . On average , subjects in the intervention group reported participating in 3.5 of 6 preventive osteoporosis activities compared with 3.4 in the control group ( P=0.5 ) . Conclusions Compared with the controls , a mailed educational intervention for osteoporosis was not associated with better knowledge , higher perceived susceptibility , or performance of preventive measures among the at-risk older adults that we studied . The intervention group demonstrated a small increase in self-efficacy . More intensive patient interventions or intervention aim ed at other aspects of the care process may be required to bring about changes that lead to a reduction in fractures", "BACKGROUND Interventions to improve the fracture prevention in nursing homes are needed . METHODS Cluster-r and omized , single-blind , controlled trial of a multi-modal quality improvement intervention . Nursing homes ( n=67 ) with > or = 10 residents with a diagnosis of osteoporosis or recent hip fracture ( n=606 ) were r and omized to receive an early or delayed intervention consisting of audit and feedback , educational modules , teleconferences , and academic detailing . Medical record abstract ion and the Minimum Data Set were used to measure the prescription of osteoporosis therapies before and after the intervention period . Analysis was at the facility-level and Generalized Estimating Equation modeling was used to account for clustering . RESULTS No significant improvements were observed in any of the quality indicators . The use of osteoporosis pharmacotherapy or hip protectors improved by 8.0 % in the intervention group and 0.6 % in the control group , but the difference was not statistically significant ( P=.72 ) . Participation in the intervention activities was low , but completion of the educational module ( odds ratio [ OR ] 4.8 , 95 % confidence interval [ CI ] , 1.9 - 12.0 ) and direct physician contact by an academic detailer ( OR 4.5 , 95 % CI , 1.1 - 18.2 ) were significantly associated with prescription of osteoporosis pharmacotherapy or hip protectors in multivariable models . CONCLUSIONS Audit-feedback and education interventions were ineffective in improving fracture prevention in the nursing home setting , although results may have been tempered by low participation in the intervention activities", "Background : Despite national guidelines recommending bone mineral density screening with dual-energy x-ray absorptiometry ( DXA ) in women aged 65 years and older , many women do not receive initial screening . Objective : To determine the effectiveness of health system and patient-level interventions design ed to increase appropriate DXA testing and osteoporosis treatment through ( 1 ) an invitation to self-refer for DXA ( self-referral ) ; ( 2 ) self-referral plus patient educational material s ; and ( 3 ) usual care ( UC , physician referral ) . Research Design : Parallel , group-r and omized , controlled trials performed at Kaiser Permanente Northwest ( KPNW ) and Kaiser Permanente Georgia ( KPG ) . Subjects : Women aged 65 years and older without a DXA in past 5 years . Measures : DXA completion rates 90 days after intervention mailing and osteoporosis medication receipt 180 days after initial intervention mailing . Results : From > 12,000 eligible women , those r and omized to self-referral were significantly more likely to receive a DXA than UC ( 13.0%–24.1 % self-referral vs. 4.9%–5.9 % UC , P DXA rates did not significantly increase with patient educational material s. Osteoporosis was detected in a greater proportion of self-referral women compared with UC ( P number needed to receive an invitation to result in a DXA in KPNW and KPG regions was approximately 5 and 12 , respectively . New osteoporosis prescription rates were low ( 0.8%–3.4 % ) but significantly greater among self-referral versus UC in KPNW . Conclusions : DXA rates significantly improved with a mailed invitation to schedule a scan without physician referral . Providing women the opportunity to self-refer may be an effective , low-cost strategy to increase access for recommended osteoporosis screening", "OBJECTIVE This study investigated the effects of general practitioner , patient , and prescription characteristics on the reduction of long-term benzodiazepine prescribing by sending a letter to chronic users . The data were analyzed with a method respecting the hierarchical data structure . STUDY DESIGN AND SETTING Data were obtained from 8,170 chronic users nested in 147 general practice s. One thous and two hundred fifty-six chronic users in 19 general practice s received a letter with the advice to reduce or stop the use of benzodiazepines after the general practitioners had attended a course on benzodiazepine use . In a three-level r and om intercept multilevel regression model , long-term prescribing of benzodiazepines was the dependent variable . RESULTS The reduction in benzodiazepine prescribing was significantly larger in the intervention than in the control group : 16 % after 6 months and 14 % after 12 months , respectively . The age of the patient , gender , and the interaction between age and gender were significant . The combination of the duration ( long acting or short acting ) with the type of benzodiazepine ( anxiolytic or hypnotic ) was an important pharmacological baseline covariate . CONCLUSIONS The reduction of benzodiazepine prescribing was mainly explained by the letter intervention and individual patient characteristics . Multilevel analysis was a worthwhile method for application in this study with its unbalanced design", "OBJECTIVE To assess the effectiveness of a multifaceted intervention to improve the management of glucocorticoid-induced osteoporosis ( GIOP ) . METHODS Of 21 rheumatologists , 11 were r and omly assigned to a 3-part intervention consisting of a lecture and discussion regarding optimal management of GIOP , a confidential doctor-specific audit regarding management of GIOP , and a reminder mailing including concise pharmacologic recommendations . The remaining 10 rheumatologists received no special education . Patients with rheumatoid arthritis ( RA ) taking oral glucocorticoids seen in the 2 months after the intervention were followed for 6 months . Medical records were assessed to determine the proportion undergoing bone mineral density testing or receiving pharmacologic interventions for GIOP during the 6 months before and 6 months after the intervention . RESULTS There were 373 patients with RA taking oral glucocorticoids whose records were assessed . Patients in both arms of the trial were similar with respect to age , sex , menopausal status , glucocorticoid dosage and duration , duration of RA , disease-modifying antirheumatic drug use , and the proportion with comorbid conditions . At baseline , there was no significant difference between the patients with respect to osteoporosis medication use ( intervention 32 % versus control 34 % ) or bone densitometry use ( intervention 9 % versus control 5 % ) . After the intervention and a 6-month followup period , there were no differences in treatment ( intervention 33 % versus control 38 % ) or bone densitometry use ( intervention 8 % versus control 8 % ) . Adjusting for patient and physician characteristics did not significantly change these results . CONCLUSION A multifaceted intervention for GIOP , including doctor education , practice audit , and treatment suggestions , had no significant benefit on testing or treatment by rheumatologists over a 6-month followup period . Other intervention approaches need to be tested", "Summary This study assessed whether osteoporosis diagnosis and treatment after an osteoporotic fracture can be increased by providing osteoporosis reading material to patients and family doctors or by watching a videocassette about osteoporosis . Educating patients about osteoporosis had little impact on whether a woman received an osteoporosis diagnosis or treatment . Introduction The purpose of this study was to investigate the impact of two education-based interventions on osteoporosis diagnosis and treatment in women ≥50 years of age after fragility fracture . Methods Six to eight months after fracture , women were r and omized into three groups : ( 1 ) control , ( 2 ) written material s , or ( 3 ) videocassette and written material s. Written material s for both the patient and physician detailed osteoporosis , fragility fracture , and available treatments ; written material s for physicians were provided through patients . The educational videocassette presented similar information as the written material , but in greater depth . Rates of osteoporosis diagnosis and treatment following intervention were compared among groups using survival analysis methods . Statistical significance was set at p At r and omization , 1,174 women were without osteoporosis diagnosis and treatment , and after follow-up , 12 % of the control group , 15 % of the written material s group ( p = 0.073 ) , and 16 % ( p = 0.036 ) of the videocassette and written material s group were diagnosed with osteoporosis ( statistical comparisons to control ) . Treatment rates were 8 % for the control group , 12 % for the written material s group ( p = 0.052 ) , and 11 % for the videocassette and written material s group ( p = 0.157 ) . At r and omization , 1,314 women were without treatment and after follow-up therapy was initiated in 10 % of the control group , 13 % of the written material s group ( p = 0.107 ) , and 13 % of the videocassette and written material s group ( p = 0.238 ) . Conclusions The educational interventions assessed in this trial were not satisfactory to increase osteoporosis diagnosis or treatment in recently fractured women to a clinical ly meaningful degree", "OBJECTIVES Osteoporosis treatment rates after a fracture are low . This study evaluated methods to increase guideline -recommended osteoporosis care postfracture . DESIGN Participants were r and omly assigned to usual care or one of two interventions . Analysis of primary outcomes used electronic data and linear regression . SETTING A Pacific Northwest nonprofit health maintenance organization . PARTICIPANTS Female patients aged 50 to 89 who suffered a fracture in 1999 and had not received bone mineral density ( BMD ) measurement or medication for osteoporosis ( n=311 ) and their primary care providers ( n=159 ) . INTERVENTION Patient-specific clinical guideline advice to the primary care provider delivered by electronic medical record ( EMR ) message or electronic reminder to the provider plus an educational letter mailed to the patient . MEASUREMENTS BMD measurement and osteoporosis medication . RESULTS At 6 months , provider reminder result ed in 51.5 % of patients receiving BMD measurement or osteoporosis medication , provider reminder plus patient education result ed in 43.1 % , and usual care result ed in 5.9 % ( P Patients aged 60 to 69 were 18 % ( 95 % confidence interval=3 - 34 ) more likely to receive BMD measurement or an osteoporosis medication than those aged 80 to 89 . CONCLUSION Patient-specific postfracture advice to the provider through an EMR message significantly increased BMD measurement and osteoporosis medication . As EMRs become more widespread , this intervention could improve osteoporosis management for many postfracture patients . Future research should identify barriers to and facilitators of care for older , high-risk patients", "Summary We conducted a multicenter , r and omized controlled trial to evaluate the impact of a population -based patient-centered post-fracture care program with a dedicated case manager , PREVention of OSTeoporosis ( PREVOST ) , on appropriate post-fracture osteoporosis management . We showed that , compared to usual care , BMD investigation post-fracture was significantly improved ( + 20 % ) by our intervention program . Introduction Our study aims to evaluate the impact of a population -based patient-centered post-fracture care program , PREVOST , on appropriate post-fracture care . Methods Multicenter , r and omized controlled trial enrolling 436 women aged 50 to 85 years and attending a French hospital , for a low-energy fracture of the wrist or humerus . R and omization was stratified by age , hospital department , and site of fracture . The intervention was performed by a trained case manager who interacted only with the patients , with repeated oral and written information about fragility fractures and osteoporosis management , and prompting them to visit their primary care physicians . Control group received usual care . The primary outcome was the initiation of an appropriate post-fracture care defined by Bone Mineral Density ( BMD ) and /or anti-osteoporotic treatment prescription at 6 months . Results At 6 months , 53 % of women in intervention group initiated a post-fracture care versus 33 % for usual care ( adjOR 2.35 , 95%CI [ 1.58–3.50 ] , p ) . Post-fracture care was more frequent after wrist than humerus fracture ( adjOR 1.93 , 95%CI [ 1.14–3.30 ] , p = 0.015 ) and decreased with age ( adjOR for 10 years increase 0.76 , 95%CI [ 0.61–0.96 ] , p = 0.02 ) . The intervention result ed in BMD prescription in 50 % of patients ( adjOR 2.10 , 95%CI [ 1.41–3.11 ] , p 0.001 ) and in BMD performance in 41 % of patients ( adjOR 2.12 , 95%CI [ 1.40–3.20 ] , p BMD increased treatment prescription ; however , only 46 % of women with a low BMD requiring a treatment according to the French guidelines received a prescription . Conclusion A patient-centered care program with a dedicated case manager can significantly improve post-fracture BMD investigation ", "Summary In a cluster r and omized trial , we evaluated the effect of a multifaceted intervention ( directed at both patient and primary care physician ) on the rates of testing and treatment of osteoporosis in postmenopausal women within six months of their wrist fracture . Compared to usual care , women in the intervention practice s were three times more likely to receive bone mineral density testing and prescribed osteoporosis treatments . Introduction Postmenopausal women with wrist fractures are at increased risk of future fragility fractures , yet they frequently do not receive evaluation and treatment for osteoporosis . We set out to evaluate a multifaceted intervention design ed to improve management of osteoporosis in older women with recent wrist fractures . Methods Cluster r and omized trial of 270 women cared for in 119 primary care practice s. We recruited postmenopausal women with an acute wrist fracture from the emergency departments of hospitals in southeastern Ontario , Canada . Family practice s were r and omly assigned to either the intervention or usual care . The intervention consisted of a mailed reminder with a summary of treatment guidelines and letter sent to the primary care physician , in addition to an educational package and letter to the women . The primary outcome was the proportion of women prescribed osteoporosis therapy within 6 months of their fracture . Results The mean age of women was 69(10.9 ) years . The intervention increased the proportion of women started on osteoporosis medications ( 28 % vs. 10 % ) of controls , adjusted OR 3.45 , 95 % CI , 1.58–7.56 , p = 0.002 ) and the proportion who had a bone mineral density ( BMD ) test ( 53.3 % vs. 26 % ) of controls , OR 3.38 , 95 % CI , 1.83–6.26 , p testing and treatment rates . Conclusion A multifaceted intervention significantly improved rates of osteoporosis treatment and BMD testing in postmenopausal women with wrist fractures", "Guidelines recommend bone density screening with dual-energy X-ray absorptiometry ( DXA ) in women 65 years or older , but There is a need to identify a systematic , effective , and generalizable way to improve osteoporosis screening . A group r and omized , controlled trial of women ≥65 years old with no DXA in the past 4 years , r and omized to receive intervention material s ( patient osteoporosis brochure and a letter explaining how to self-schedule a DXA scan ) versus usual care ( control ) was undertaken . Outcome of interest was DXA completion . Of 2997 women meeting inclusion criteria , 977 were r and omized to the intervention group . A total of 17.3 % of women in the intervention group completed a DXA , compared to 5.2 % in the control group ( 12.1 % difference , p was greater in main clinic patients compared to satellite clinic patients ( 20.9 % main clinic versus 10.1 % satellite clinic ) . The cost to print and mail the intervention was $ 0.79 per patient , per mailing . The number of women to whom intervention needed to be mailed to yield one extra DXA performed was 9 , at a cost of $ 7.11 . DXA scan completion was significantly improved through use of a mailed osteoporosis brochure and the availability for patients to self-schedule . This simple approach may be an effective component of a multifaceted quality improvement program to increase rates of osteoporosis screening ", "Background Depression is a common mental health disorder for which clinical practice guidelines have been developed . Prior systematic review s have identified complex organizational interventions , such as collaborative care , as effective for guideline implementation ; yet , many healthcare delivery organizations are interested in less re source -intensive methods to increase provider adherence to guidelines and guideline -concordant practice s. The objective of this systematic review was to assess the effectiveness of healthcare provider interventions that aim to increase adherence to evidence -based treatment of depression in routine clinical practice . Methods We search ed five data bases through August 2017 using a comprehensive search strategy to identify English- language r and omized controlled trials ( RCTs ) in the quality improvement , implementation science , and behavior change literature that evaluated outpatient provider interventions , in the absence of practice re design efforts , to increase adherence to treatment guidelines or guideline -concordant practice s for depression . We used meta- analysis to summarize odds ratios , st and ardized mean differences , and incidence rate ratios , and assessed quality of evidence ( QoE ) using the GRADE approach . Results Twenty-two RCTs promoting adherence to clinical practice guidelines or guideline -concordant practice s met inclusion criteria . Studies evaluated diverse provider interventions , including distributing guidelines to providers , education/training such as academic detailing , and combinations of education with other components such as targeting implementation barriers . Results were heterogeneous and analyses comparing provider interventions with usual clinical practice did not indicate a statistically significant difference in guideline adherence across studies . There was some evidence that provider interventions improved individual outcomes such as medication prescribing and indirect comparisons indicated more complex provider interventions may be associated with more favorable outcomes . We did not identify types of provider interventions that were consistently associated with improvements across indicators of adherence and across studies . Effects on patients ’ health in these RCTs were inconsistent across studies and outcomes . Conclusions Existing RCTs describe a range of provider interventions to increase adherence to depression guidelines . Low QoE and lack of replication of specific intervention strategies across studies limited conclusions that can be drawn from the existing research . Continued efforts are needed to identify successful strategies to maximize the impact of provider interventions on increasing adherence to evidence -based treatment for depression . Trial registration PROSPERO record CRD42017060460 on", "OBJECTIVE Distal radius fracture ( DRF ) in postmenopausal women is often the first clinical sign of osteoporosis ( OP ) . Despite the availability of effective treatments , only a minority of patients who sustain a fragility fracture are tested for OP . The purpose of this study was to examine whether a simple intervention by the hospital staff increases rates of OP workup . MATERIAL S AND METHODS We conducted a prospect i ve r and omized clinical trial . Ninety nine patients after DRF were r and omized to two groups . Both groups were contacted after their fracture and were asked to answer a question naire and were informed about the possible relationship between DRF and OP . In the intervention group , patients were sent an explanatory pamphlet and a letter to their primary care physician . An additional survey was conducted to establish whether the intervention improved the number of patients who undergo OP workup . RESULTS The intervention increased the proportion of patients who turned to their primary care physician from 22.9 % to 68.6 % , and increased the proportion of patients undergoing OP workup from 14.3 % to 40 % ( p Women with DRF who receive an explanation about possible OP implication s and are sent explanatory material s are more likely to undergo OP workup" ]	41188ff6-06ff-11f0-808a-c43d1ab1c353
AIM To assess , through a systematic review , evidence for the effects of antiarrhythmic drugs ( AADs ) on cardiovascular ( CV ) hospitalization and mortality . MATERIAL S & METHODS English language articles were identified using MEDLINE , EMBASE and the Cochrane Clinical Trial Registry and were screened for study applicability and method ological quality . RESULTS Out of 3526 identified studies , 38 were selected for analysis ( 19 evaluated individual AADs , 13 compared rate- versus rhythm-control strategies , and 6 evaluated multiple AADs but did not report outcomes for individual agents ) . None of the studies examining individual AADs employed the CV hospitalization end point used in ATHENA ( the reference trial ) . There were no head-to-head comparisons of individual AADs on CV hospitalization . Most high- quality studies used multidrug rate- versus rhythm-control strategies . CONCLUSION Assessment of the comparative effectiveness of individual AADs on CV hospitalization and mortality end points is not possible with the current evidence	[ "BACKGROUND Atrial fibrillation ( AF ) is a very common cardiac arrhythmia , and is associated with an increased mortality in patients with hypertension . Whether the best therapeutic approach for these patients is to restore sinus rhythm ( SR ) or to adequately control the ventricular rate is still controversial . The aim of this study is to compare both strategies in patients with hypertension . METHODS AND RESULTS Two hundred and twenty-one patients with hypertension and AF of duration > 48 h were r and omly assigned to either the rhythm ( n=155 ) or rate ( n=66 ) control group . Exercise capacity was improved in the rhythm control group in the 1st year of the study ( p embolic event rate and the total mortality between the 2 groups at the end of the study ( p = NS ) . CONCLUSIONS Although restoring and maintaining SR had a beneficial effect on exercise capacity in patients with hypertension and AF , no significant difference was found in terms of the total mortality and the embolic event rates . Thus , rate control is an acceptable primary strategy in patients with AF and hypertension", "Recent trials have favoured ventricular rate control in atrial fibrillation ( AF ) management , however the present study investigated whether the restoration and maintenance of sinus rhythm with long-term anticoagulation therapy was superior in terms of embolic events and death in 534 patients with an AF duration > 48 h. Patients were r and omized and received sinus rhythm control with either aspirin ( group 1 ) or warfarin ( group 2 ) , or they were given ventricular rate control ( group 3 ) . Cardioversion to sinus rhythm was attempted in 425 patients and was successful in 387 ( 91.1 % ) of them . After 3 years ' follow-up there were 12 , two and 15 embolic events in groups 1 , 2 and 3 respectively ( significant difference between groups 1 and 2 , and 2 and 3 ) and overall mortalities were four , two and 12 , respectively ( significant difference between groups 2 and 3 ) . It is concluded that patients with an AF duration > 48 h might benefit considerably from sinus rhythm restoration and long-term warfarin therapy in terms of embolic events and mortality", "In a controlled study comprising 176 patients , quinidine in the form of Kinidin Durules was found to reduced significantly the recurrence of the atrial fibrillation during a 1-year follow-up period after successful electric shock conversion . After one year , 51 per cent ( 52/101 ) of the patients in the quinidine group , and 28 per cent ( 21/75 ) in the control group remained in sinus rhythm ( P smaller than 0.001 ) . No less than 43 per cent of the patients converted to sinus rhythm during treatment with maintenance doses of quinidine sulphate before intended DC conversion . Gastrointestinal side-effects were not uncommon , and caused interruption of quinidine treatment in some cases", "We evaluated the efficacy and safety of azimilide , a new class III antiarrhythmic agent that blocks both the slow and fast components of the cardiac-delayed rectifier potassium currents in 4 r and omized , double-blind , placebo-controlled trials with similar protocol s. The purpose of this study was to assess the relation between dose and effect . A total of 1,380 patients with a documented history of symptomatic atrial fibrillation ( AF ) , atrial flutter , or both , were enrolled . After a 3-day loading period during which the assigned dose was given twice a day , subjects received placebo or azimilide ( 35 , 50 , 75 , 100 , or 125 mg once a day ) for the duration of the study period . The primary end point of the studies was the time to symptomatic arrhythmia recurrence with a transtelephonic electrocardiogram typical of AF , atrial flutter , or paroxysmal supraventricular tachycardia . For each study , Kaplan-Meier estimates of the median time to recurrence were computed for placebo and for each azimilide dose . Cox proportional-hazards modeling was used to estimate hazard ratios for each active dose . Each of the 2 highest azimilide doses ( 100 and 125 mg/day ) significantly prolonged the time to recurrence of arrhythmia . For the 100 mg/day dose , the hazard ratio was 1.34 , 95 % confidence interval 1.05 to 1.72 ; p = 0.02 . For the 125 mg/day dose , the hazard ratio was 1.32 , 95 % confidence interval 1.07 to 1.62 ; p = 0.01 . Patients with a history of either ischemic heart disease or congestive heart failure had a significantly greater treatment effect from azimilide than those without it . Torsades de Pointes occurred in 0.9 % of patients receiving either of the 2 effective doses . Thus , doses of azimilide AF , whereas doses of 100 and 125 mg/day are effective with an acceptable risk of serious toxicity", "BACKGROUND Azimilide dihydrochloride ( azimilide ) is an investigational antiarrhythmic drug that has been tested in patients with a variety of arrhythmias . In patients with atrial fibrillation , it has shown excellent efficacy in some previous trials and minimal efficacy in others . METHODS Patients who had symptomatic atrial fibrillation for > 48 hours but this multicenter , r and omized , placebo-controlled clinical trial . Patients were admitted to a hospital and r and omly assigned to receive either azimilide 125 mg or a matched placebo twice daily for 3 days and then once daily . Patients who were in sinus rhythm spontaneously or had sinus rhythm restored by electric cardioversion on day 4 were discharged from the hospital . Recurrence of atrial fibrillation was documented by electrocardiogram . In the primary efficacy analysis , time to recurrence in the 2 treatment groups was compared with the log-rank test in the subgroup of patients with structural heart disease . Safety was assessed as deaths , adverse events , and serious adverse events . RESULTS A total of 446 patients were r and omized in the study ; 314 were in the subgroup with structural heart disease . The median time to arrhythmia recurrence in both treatment groups with structural heart disease was 13 days , and the difference between treatments was not significant ( P = .4596 , n = 314 ) . The relative risk for recurrence ( placebo : azimilide ) was 1.104 ( 95 % CI 0.849 - 1.436 ) . There was 1 death in the placebo group and 3 in the azimilide group . CONCLUSIONS Azimilide did not demonstrate clinical ly important or statistically significant efficacy in reducing the risk for arrhythmia recurrence in patients with structural heart disease who were in atrial fibrillation and converted to sinus rhythm", "BACKGROUND Dronedarone is a new antiarrhythmic drug that is being developed for the treatment of patients with atrial fibrillation . METHODS We conducted a multicenter trial to evaluate the use of dronedarone in 4628 patients with atrial fibrillation who had additional risk factors for death . Patients were r and omly assigned to receive dronedarone , 400 mg twice a day , or placebo . The primary outcome was the first hospitalization due to cardiovascular events or death . Secondary outcomes were death from any cause , death from cardiovascular causes , and hospitalization due to cardiovascular events . RESULTS The mean follow-up period was 21+/-5 months , with the study drug discontinued prematurely in 696 of the 2301 patients ( 30.2 % ) receiving dronedarone and in 716 of the 2327 patients ( 30.8 % ) receiving placebo , mostly because of adverse events . The primary outcome occurred in 734 patients ( 31.9 % ) in the dronedarone group and in 917 patients ( 39.4 % ) in the placebo group , with a hazard ratio for dronedarone of 0.76 ( 95 % confidence interval [ CI ] , 0.69 to 0.84 ; P deaths ( 5.0 % ) in the dronedarone group and 139 ( 6.0 % ) in the placebo group ( hazard ratio , 0.84 ; 95 % CI , 0.66 to 1.08 ; P=0.18 ) . There were 63 deaths from cardiovascular causes ( 2.7 % ) in the dronedarone group and 90 ( 3.9 % ) in the placebo group ( hazard ratio , 0.71 ; 95 % CI , 0.51 to 0.98 ; P=0.03 ) , largely due to a reduction in the rate of death from arrhythmia with dronedarone . The dronedarone group had higher rates of bradycardia , QT-interval prolongation , nausea , diarrhea , rash , and an increased serum creatinine level than the placebo group . Rates of thyroid- and pulmonary-related adverse events were not significantly different between the two groups . CONCLUSIONS Dronedarone reduced the incidence of hospitalization due to cardiovascular events or death in patients with atrial fibrillation . ( Clinical Trials.gov number , NCT00174785 .", "Background —Expectations that reestablishing and maintaining sinus rhythm in patients with atrial fibrillation might improve survival were disproved in the Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) study . This report describes the cause-specific modes of death in the AFFIRM treatment groups . Methods and Results —All deaths in patients enrolled in AFFIRM underwent blinded review by the AFFIRM Events Committee , and a mode of death was assigned . In AFFIRM , 2033 patients were r and omized to a rhythm-control strategy and 2027 patients to a rate-control strategy . During a mean follow-up of 3.5 years , there were 356 deaths in the rhythm-control patients and 310 deaths in the rate-control patients ( P = 0.07 ) . In the rhythm-control group , 129 patients ( 9 % ) died of a cardiac cause , and in the rate-control group , 130 patients ( 10 % ) died ( P = 0.95 ) . Both groups had similar rates of arrhythmic and nonarrhythmic cardiac deaths . The numbers of vascular deaths were similar in the 2 groups : 35 ( 3 % ) in the rhythm-control group and 37 ( 3 % ) in the rate-control group ( P = 0.82 ) . There were no differences in the rates of ischemic stroke and central nervous system hemorrhage . In the rhythm-control group , there were 169 noncardiovascular deaths ( 47.5 % of the total number of deaths ) , whereas in the rate-control arm , there were 113 noncardiovascular deaths ( 36.5 % of the total number of deaths ) ( P = 0.0008 ) . Differences in noncardiovascular death rates were due to pulmonary and cancer-related deaths . Conclusions —Management of atrial fibrillation with a rhythm-control strategy conferred no advantage over a rate-control strategy in cardiac or vascular mortality and may be associated with an increased noncardiovascular death rate", "Background —In patients with left ventricular dysfunction , atrial fibrillation and flutter ( AF and AFl , respectively ) are common arrhythmias associated with increased morbidity and mortality . The present study investigated the potential of dofetilide in AF-AFl patients with left ventricular dysfunction to restore and maintain sinus rhythm , which might reduce mortality and hospitalizations . Methods and Results —In the Danish Investigations of Arrhythmia and Mortality ON Dofetilide ( DIAMOND ) studies , 506 patients were in AF-AFl at baseline . Over the course of study , cardioversion occurred in 148 ( 59 % ) dofetilide- and 86 ( 34 % ) placebo-treated patients . In these patients , the probability of maintaining sinus rhythm for 1 year was 79 % with dofetilide versus 42 % with placebo ( P Dofetilide had no effect on all-cause mortality , but restoration and maintenance of sinus rhythm was associated with significant reduction in mortality ( risk ratio [ RR ] , 0.44 ; 95 % CI , 0.30 to 0.64;P dofetilide therapy was associated with a significantly lower risk ratio versus placebo for either all-cause ( RR , 0.70 ; 95 % CI , 0.56 to 0.89;P ≤0.005 ) or congestive heart failure ( RR , 0.69 ; 95 % CI , 0.51 to 0.93;P ≤0.02 ) rehospitalization . Conclusions —Dofetilide is safe and increases the probability of obtaining and maintaining sinus rhythm in patients with structural heart disease . The present study suggests that restoration of sinus rhythm is associated with improved survival", "BACKGROUND Dronedarone is a novel antiarrhythmic drug with electrophysiological properties that are similar to those of amiodarone , but it does not contain iodine and thus does not cause iodine-related adverse reactions . Therefore , it may be of value in the treatment of patients with heart failure . METHODS In a multicenter study with a double-blind design , we planned to r and omly assign 1000 patients who were hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunction to receive 400 mg of dronedarone twice a day or placebo . The primary end point was the composite of death from any cause or hospitalization for heart failure . RESULTS After inclusion of 627 patients ( 310 in the dronedarone group and 317 in the placebo group ) , the trial was prematurely terminated for safety reasons , at the recommendation of the data and safety monitoring board , in accordance with the board 's predefined rules for termination of the study . During a median follow-up of 2 months , 25 patients in the dronedarone group ( 8.1 % ) and 12 patients in the placebo group ( 3.8 % ) died ( hazard ratio in the dronedarone group , 2.13 ; 95 % confidence interval [ CI ] , 1.07 to 4.25 ; P=0.03 ) . The excess mortality was predominantly related to worsening of heart failure--10 deaths in the dronedarone group and 2 in the placebo group . The primary end point did not differ significantly between the two groups ; there were 53 events in the dronedarone group ( 17.1 % ) and 40 events in the placebo group ( 12.6 % ) ( hazard ratio , 1.38 ; 95 % CI , 0.92 to 2.09 ; P=0.12 ) . More increases in the creatinine concentration were reported as serious adverse events in the dronedarone group than in the placebo group . CONCLUSIONS In patients with severe heart failure and left ventricular systolic dysfunction , treatment with dronedarone was associated with increased early mortality related to the worsening of heart failure . ( Clinical Trials.gov number , NCT00543699 .", "AIMS Permanent atrial fibrillation develops in many patients after ablation and pacing therapy . We compared a strategy that initially allowed patients to remain in atrial fibrillation with a strategy that initially attempted to restore and maintain sinus rhythm . METHODS AND RESULTS In this multicentre r and omized controlled trial , 68 patients affected by severely symptomatic paroxysmal atrial fibrillation were assigned , after successful atrioventricular junction ablation and pacing treatment , to antiarrhythmic drug therapy with amiodarone , propafenone , flecainide or sotalol and were compared with 69 patients assigned , after successful AV junction ablation and pacing treatment , to no antiarrhythmic drug therapy . The patients were followed-up for 12 to 24 months ( mean 16+/-4 ) . The drug arm patients had a 57 % reduction in the risk of developing permanent atrial fibrillation ( 21 % vs 37 % , P=0.02 ) . Evaluation after 12 months revealed similar quality of life scores and echocardiographic parameters in the two groups , but the drug arm patients had more episodes of heart failure and hospitalizations ( P=0.05 ) . The outcome was similar between the 40 patients who developed permanent atrial fibrillation and the 97 who did not . CONCLUSION Conventional antiarrhythmic therapy reduces the risk of development of permanent atrial fibrillation after ablation and pacing therapy . The present data do not support the concept that the development of permanent atrial fibrillation is related to an adverse outcome when a perfect control of heart rate is obtained by ablation and pacing", "Atrial fibrillation ( AF ) is a very common cardiac arrhythmia with an increased mortality in patients with heart failure . Whether the best therapeutic approach to these patients is to restore sinus rhythm or to adequately control the ventricular rate is still controversial . The aim of this study was to compare both strategies in patients with AF and nonischemic heart failure . One hundred and fifty-four patients with AF duration greater than 48 hours and nonischemic left ventricular dysfunction were r and omized either to a rhythm ( n = 84 ) or rate ( n = 74 ) control group . The composite end points of the study were embolism , death , and exercise capacity . The average age of the patients was 61 + /- 10 years in the rhythm control group and 58 + /- 12 years in the rate control group ( P = NS ) . The average follow-up period was 35 + /- 21 months in the rhythm control group and 37 + /- 19 months in the rate control group ( P = NS ) . In the first year of the study , exercise capacity and left ventricular ejection fraction ( LVEF ) were improved in the rhythm control group compared to the exercise capacity and LVEF of the rate control group ( P embolic event rate between the two groups ( P = NS ) . The mortality rate , especially for death due to pump failure , was significantly higher in the rate control group at the end of the study ( P mortality and exercise capacity in patients with nonischemic heart failure and AF", "BACKGROUND Arrhythmias cause much morbidity and mortality after myocardial infa rct ion , but in previous trials , antiarrhythmic drug therapy has not been convincingly effective . Dofetilide , a new class III agent , was investigated for effects on all-cause mortality and morbidity in patients with left-ventricular dysfunction after myocardial infa rct ion . METHODS In 37 Danish coronary-care units , 1510 patients with severe left-ventricular dysfunction ( wall motion index were enrolled in a r and omised , double-blind study comparing dofetilide ( n=749 ) with placebo ( n=761 ) . The primary endpoint was all-cause mortality . Secondary endpoints included cardiac and arrhythmic mortality and total arrhythmic deaths . Analyses were by intention to treat . FINDINGS No significant differences were found between the dofetilide and placebo groups in all-cause mortality ( 230 [ 31 % ] vs 243 [ 32 % ] ) , cardiac mortality ( 191 [ 26 % ] vs 212 [ 28 % ] ) , or total arrhythmic deaths ( 129 [ 17 % ] vs 140 [ 18 % ] ) . Atrial fibrillation or flutter was present in 8 % of the patients at study entry . In these patients , dofetilide was significantly better than placebo at restoring sinus rhythm ( 25 of 59 vs seven of 56 ; p=0.002 ) . There were seven cases of torsade de pointes ventricular tachycardia , all in the dofetilide group . INTERPRETATION In patients with severe left-ventricular dysfunction and recent myocardial infa rct ion , treatment with dofetilide did not affect all-cause mortality , cardiac mortality , or total arrhythmic deaths . Dofetilide was effective in treating atrial fibrillation or flutter in this population", "OBJECTIVES We compared ablation strategy with antiarrhythmic drug therapy ( ADT ) in patients with paroxysmal atrial fibrillation ( PAF ) . BACKGROUND Atrial fibrillation ( AF ) ablation strategy is superior to ADT in patients with an initial history of PAF , but its role in patients with a long history of AF as compared with ADT remains a challenge . METHODS One hundred ninety-eight patients ( age , 56 + /- 10 years ) with PAF of 6 + /- 5 years ' duration ( mean AF episodes 3.4/month ) who had failed ADT were r and omized to AF ablation by circumferential pulmonary vein ablation ( CPVA ) or to the maximum tolerable doses of another ADT , which included flecainide , sotalol , and amiodarone . Crossover to CPVA was allowed after 3 months of ADT . RESULTS By Kaplan-Meier analysis , 86 % of patients in the CPVA group and 22 % of those in the ADT group who did not require a second ADT were free from recurrent atrial tachyarrhythmias ( AT ) ( p CPVA and ADT groups , respectively , were AT-free . Ejection fraction , hypertension , and age independently predicted AF recurrences in the ADT group . Circumferential pulmonary vein ablation was associated with fewer cardiovascular hospitalizations ( p transient ischemic attack and 1 pericardial effusion occurred in the CPVA group ; side effects of ADT were observed in 23 patients . CONCLUSIONS Circumferential pulmonary vein ablation is more successful than ADT for prevention of PAF with few complications . Atrial fibrillation ablation warrants consideration in selected patients in whom ADT had already failed and maintenance of sinus rhythm is desired . ( A Controlled R and omized Trial of CPVA Versus Antiarrhythmic Drug Therapy in for Paroxysmal AF : APAF/01 ; http:// clinical trials.gov/ct/show ; NCT00340314 )", "BACKGROUND Atrial tachyarrhythmias ( ATAs ) are mainly treated by pharmacologic therapy for rate control or rhythm control . The aim of our study was to compare sotalol ( S ) versus beta-blocking agents ( BB ) in terms of prevention of ATA , cardioversions ( CVs ) , and cardiovascular hospitalizations ( H ) in patients paced for bradycardia-tachycardia form of sinus node disease ( BT-SND ) . METHODS One hundred thirty-five patients ( 67 males , aged 73 + /- 7 years ) were enrolled in a prospect i ve , parallel , r and omized , single-blind , multicenter study . All patients received a dual chamber rate adaptive pacemaker ; after 1 month , 66 patients were r and omly assigned to BB ( 62 + /- 26 and 104 + /- 47 mg/d for atenolol and metoprolol , respectively ) and 69 patients to S ( 167 + /- 66 mg/d ) . RESULTS After an observation period of 12 months , the percentage of patients free from ATA recurrences was 29 % in both BB and S group . Cardioversion and H were significantly ( P Kaplan-Meier survival analysis showed a nonsignificant trend toward a lower incidence of the composite end point ( CV + H ) among BB patients . CONCLUSIONS In the complex context of \" hybrid therapy \" in patients with BT-SND implanted with a modern dual chamber rate adaptive pacemaker device delivering atrial antitachycardia pacing , no differences were found between the use of beta-blocker and the use of S , at the relatively low dose achieved after clinical titration , in terms of prevention of cardiovascular H or need for atrial CV", "BACKGROUND The restoration and maintenance of sinus rhythm is a desirable goal in patients with atrial fibrillation , because the prevention of recurrences can improve cardiac function and relieve symptoms . Uncontrolled studies have suggested that amiodarone in low doses may be more effective and safer than other agents in preventing recurrence , but this agent has not been tested in a large , r and omized trial . METHODS We undertook a prospect i ve , multicenter trial to test the hypothesis that low doses of amiodarone would be more efficacious in preventing recurrent atrial fibrillation than therapy with sotalol or propafenone . We r and omly assigned patients who had had at least one episode of atrial fibrillation within the previous six months to amiodarone or to sotalol or propafenone , given in an open-label fashion . The patients in the group assigned to sotalol or propafenone underwent a second r and omization to determine whether they would receive sotalol or propafenone first ; if the first drug was unsuccessful the second agent was prescribed . Loading doses of the drugs were administered and electrical cardioversion was performed ( if necessary ) within 21 days after r and omization for all patients in both groups . The follow-up period began 21 days after r and omization . The primary end point was the length of time to a first recurrence of atrial fibrillation . RESULTS Of the 403 patients in the study , 201 were assigned to amiodarone and 202 to either sotalol ( 101 patients ) or propafenone ( 101 patients ) . After a mean of 16 months of follow-up , 71 of the patients who were assigned to amiodarone ( 35 percent ) and 127 of those who were assigned to sotalol or propafenone ( 63 percent ) had a recurrence of atrial fibrillation ( P Adverse events requiring the discontinuation of drug therapy occurred in 18 percent of the patients receiving amiodarone , as compared with 11 percent of those treated with sotalol or propafenone ( P=0.06 ) . CONCLUSIONS Amiodarone is more effective than sotalol or propafenone for the prevention of recurrences of atrial fibrillation", "CONTEXT Amiodarone effectively suppresses atrial fibrillation but causes many adverse events . OBJECTIVE To compare major events in patients r and omized to receive episodic amiodarone treatment with those who received continuous amiodarone treatment while still aim ing to prevent atrial fibrillation . DESIGN , SETTING , AND PARTICIPANTS A r and omized trial of 209 ambulatory patients with recurrent symptomatic persistent atrial fibrillation , conducted from December 2002 through March 2007 at 7 Dutch medical centers . INTERVENTION Patients were r and omly assigned to receive either episodic or continuous amiodarone treatment after electrical cardioversion following amiodarone loading . Episodic amiodarone treatment was discontinued after a month of sinus rhythm and reinitiated if atrial fibrillation relapsed ( 1 month peri-electrical cardioversion ) . In the continuous treatment group amiodarone was maintained throughout . MAIN OUTCOME MEASURES The primary end point was a composite of amiodarone and underlying heart disease-related major events . The secondary end points were all-cause mortality and cardiovascular hospitalizations . RESULTS After a median follow-up of 2.1 years ( range , 0.4 - 2.5 years ) , 51 ( 48 % ) of those receiving episodic treatment vs 64 ( 62 % ) receiving continuous treatment had sinus rhythm ( P = .05 ) . There were 85 atrial fibrillation recurrences ( 80 % ) among the episodic treatment group vs 56 ( 54 % ) in the continuous treatment group ( P primary composite end point between each group ( 37 [ 35 % ] episodic vs 34 [ 33 % ] continuous ; incidence rate difference , 0.2 ; 95 % confidence interval [ CI ] , -10.2 to 10.6 ) . However , there were nonstatistically significant differences in the incidence of amiodarone-related major events ( 20 [ 19 % ] episodic vs 25 [ 24 % ] continuous ; incidence rate difference , -2.0 ; 95 % CI , -8.7 to 4.6 ) and underlying heart disease-related major events ( 17 [ 16 % ] episodic vs 9 [ 9 % ] continuous ; incidence rate difference , 3.6 ; 95 % CI , -1.6 to 8.7 ) . All-cause mortality and cardiovascular hospitalizations were higher among those receiving episodic treatment ( 56 [ 53 % ] vs 35 [ 34 % ] , P = .02 ) . CONCLUSIONS In this study population , there was no difference in the composite of amiodarone and cardiac major adverse events between groups . However , patients receiving episodic treatment had a significantly increased rate of atrial fibrillation recurrence and a significantly higher rate of all-cause mortality and cardiovascular hospitalizations . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00392431", "BACKGROUND This study was conducted to compare rate- and rhythm-control therapy in patients with persistent atrial fibrillation ( AF ) and mild to moderate chronic heart failure ( CHF ) . Rate control is not inferior to rhythm control in preventing mortality and morbidity in patients with AF . In CHF , this issue is still unsettled . METHODS In this predefined analysis of the RACE study , a total of 261 patients were in New York Heart Association ( NYHA ) classes II and III at baseline . These patients were analyzed . The primary end point was a composite of cardiovascular mortality , hospitalization for CHF , thromboembolic complications , bleeding , pacemaker implantation , and life-threatening drug side effects . Furthermore , quality of life was compared . RESULTS After 2.3 + /- 0.6 years , the primary end point occurred in 29 ( 22.3 % ) of the 130 rate-control patients and in 32 ( 24.4 % ) of the 131 rhythm-control patients . More cardiovascular deaths , hospitalization for CHF , and bleeding occurred under rate control . Thromboembolic complications , drug side effects , and pacemaker implantation were more frequent under rhythm control . Quality of life did not differ between strategies . In patients successfully treated with rhythm control , the prevalence of end points was not different from those who were in AF at study end . However , the type of end point was different : mortality , bleeding , hospitalization for heart failure , and pacemaker implantation occurred less frequently . CONCLUSIONS In patients with mild to moderate CHF , rate control is not inferior to rhythm control . However , if sinus rhythm can be maintained , outcome may be improved . A prospect i ve r and omized trial is necessary to confirm these results", "STUDY OBJECTIVES The relative risks and benefits of strategies of rate control vs rhythm control in patients with atrial fibrillation ( AF ) remain to be fully explored . DESIGN The How to Treat Chronic Atrial Fibrillation ( HOT CAFE ) Polish trial was design ed to evaluate in a r and omized , multicenter , and prospect i ve manner the feasibility and long-term outcomes of rate control vs rhythm control strategies in patients with persistent AF . PATIENTS Our study population comprised 205 patients ( 134 men and 71 women ; mean [ + /- SD ] age , 60.8 + /- 11.2 years ) with a mean AF duration of 273.7 + /- 112.4 days . The mean observation period was 1.7 + /- 0.4 years . One hundred one patients were r and omly assigned to the rate control group and received rate-slowing therapy guided by repeated 24-h Holter monitoring . Direct current cardioversion and atrioventricular junctional ablation with pacemaker placement were alternative nonpharmacologic strategies for patients with tachycardia that was resistant to medical therapy . One hundred four patients were r and omized to sinus rhythm restoration and maintenance using serial cardioversion supported by a predefined stepwise antiarrhythmic drug regimen ( ie , disopyramide , propafenone , sotalol , and amiodarone ) . In both groups , thromboembolic prophylaxis followed current guidelines . MEASUREMENTS AND RESULTS At the end of follow-up , 63.5 % of patients in the rhythm control arm remained in sinus rhythm . No significant differences in the composite end point ( ie , all-cause mortality , number of thromboembolic events , or major bleeding ) were found between the rate control group and the rhythm control group ( odds ratio , 1.98 ; 95 % confidence interval , 0.28 to 22.3 ; p > 0.71 ) . The incidence of hospital admissions was much lower in the rate control arm ( 12 % vs 74 % , respectively ; p New York Heart Association functional class improved in both study groups , while mean exercise tolerance , as measured by the maximal treadmill workload , improved only in the rhythm control group ( 5.2 + /- 5.1 vs 7.6 + /- 3.3 metabolic equivalents , respectively ; p mean left ventricular fractional shortening ( 29 + /- 7 % vs 31 + /- 7 % , respectively ; p pulmonary embolism occurred in the rate control group despite oral anticoagulation therapy , while three patients in the rhythm control arm of the study experienced ischemic strokes ( not significant ) . CONCLUSIONS The Polish HOT CAFE study revealed no significant differences in major end points between the rate control group and the rhythm control group", "OBJECTIVES This study was design ed to compare two treatment strategies in patients with atrial fibrillation(AF ) : rhythm-control ( restoration and maintenance of sinus rhythm ) and rate-control ( pharmacologic or invasive rate-control and anticoagulation ) . BACKGROUND Atrial fibrillation is the most common arrhythmia . It is unclear whether a strategy of rhythm- or rate-control is better in terms of mortality , morbidity , and quality of life . METHODS The Strategies of Treatment of Atrial Fibrillation ( STAF ) multicenter pilot trial r and omized 200 patients ( 100 per group ) with persistent AF to rhythm- or rate-control . The combined primary end point was a combination of death , cardiopulmonary resuscitation , cerebrovascular event , and systemic embolism . RESULTS After 19.6 + /- 8.9 months ( range 0 to 36 months ) there was no difference in the primary end point between rhythm-control ( 9/100 ; 5.54%/year ) and rate-control ( 10/100 ; 6.09%/year ; p = 0.99 ) . The percentage of patients in sinus rhythm in the rhythm-control group after up to four cardioversions during the follow-up period ( rate-control group ) was 23 % ( 0 % ) at 36 months . Eighteen primary end points occurred in atrial fibrillation ; only one occurred in sinus rhythm ( p = 0.049 ) . CONCLUSIONS The STAF pilot study showed no differences between the two treatment strategies in all end points except hospitalizations . These data suggest that there was no benefit in attempting rhythm-control in these patients with a high risk of arrhythmia recurrence . It remains unclear whether the results in the rhythm-control group would have been better if sinus rhythm had been maintained in a higher proportion of patients , as all but one end point occurred during AF", "AIMS To compare outcome of AF patients with effective rhythm control with patients treated with rate control . METHODS AND RESULTS Out of the 266 AF patients r and omized to rhythm control in the RACE study , 49 patients turned to long-term sinus rhythm and were continuously treated with oral anticoagulation . The incidence of the primary endpoint in these patients was compared to that in 178 patients out of the initial 256 rate-control patients of RACE who were in AF and using oral anticoagulation continuously . Baseline characteristics of both groups were not different . After a mean follow-up of 2.3+/-0.6 years , the primary endpoint ( a composite of cardiovascular mortality , heart failure , thrombo-embolic complications ( TECs ) , bleeding , serious adverse effects of antiarrhythmic drugs and pacemaker implants ) was 22.4 % in the rhythm-control group vs. 15.2 % in the rate-control group . Multivariable regression analysis indicated coronary artery disease , heart failure , and digitalis as independent risk indicators of cardiovascular morbidity and mortality . Chronic sinus rhythm did not matter . CONCLUSION Among patients who remained on warfarin , those who mostly were maintained in sinus rhythm under a rhythm-control strategy did not have a superior prognosis compared to those who remained in AF under a rate-control strategy", "BACKGROUND Maintenance of sinus rhythm is the main therapeutic goal in patients with atrial fibrillation . However , recurrences of atrial fibrillation and side effects of antiarrhythmic drugs offset the benefits of sinus rhythm . We hypothesized that ventricular rate control is not inferior to the maintenance of sinus rhythm for the treatment of atrial fibrillation . METHODS We r and omly assigned 522 patients who had persistent atrial fibrillation after a previous electrical cardioversion to receive treatment aim ed at rate control or rhythm control . Patients in the rate-control group received oral anticoagulant drugs and rate-slowing medication . Patients in the rhythm-control group underwent serial cardioversions and received antiarrhythmic drugs and oral anticoagulant drugs . The end point was a composite of death from cardiovascular causes , heart failure , thromboembolic complications , bleeding , implantation of a pacemaker , and severe adverse effects of drugs . RESULTS After a mean ( + /-SD ) of 2.3+/-0.6 years , 39 percent of the 266 patients in the rhythm-control group had sinus rhythm , as compared with 10 percent of the 256 patients in the rate-control group . The primary end point occurred in 44 patients ( 17.2 percent ) in the rate-control group and in 60 ( 22.6 percent ) in the rhythm-control group . The 90 percent ( two-sided ) upper boundary of the absolute difference in the primary end point was 0.4 percent ( the prespecified criterion for noninferiority was 10 percent or less ) . The distribution of the various components of the primary end point was similar in the rate-control and rhythm-control groups . CONCLUSIONS Rate control is not inferior to rhythm control for the prevention of death and morbidity from cardiovascular causes and may be appropriate therapy in patients with a recurrence of persistent atrial fibrillation after electrical cardioversion", "OBJECTIVES The goal of this study was to evaluate the relationship between the presence of sinus rhythm and outcomes in patients with a history of congestive heart failure ( CHF ) and atrial fibrillation ( AF ) . BACKGROUND The value of sinus rhythm maintenance in patients with AF and heart failure ( HF ) is uncertain . METHODS A total of 1,376 patients with AF , ejection fraction were r and omized to a rhythm- or rate-control strategy . Detailed efficacy analyses were used to evaluate the independent effects of treatment strategy and the presence of sinus rhythm on cardiovascular outcomes . RESULTS Overall , 445 ( 32 % ) patients died and 402 ( 29 % ) experienced worsening HF . The rhythm-control strategy was not predictive of cardiovascular mortality ( hazard ratio [ HR ] : 0.90 , 95 % confidence interval [ CI ] : 0.70 to 1.16 ; p = 0.41 ) , all-cause death ( HR : 0.86 , 95 % CI : 0.69 to 1.08 ; p = 0.19 ) , or worsening HF ( HR : 0.86 , 95 % CI : 0.68 to 1.10 ; p = 0.23 ) . In analyses devised to isolate the effect of underlying rhythm , sinus rhythm was not associated with cardiovascular mortality [ HR : 1.22 , 95 % CI : 0.80 to 1.87 ; p = 0.35 ) , total mortality [ HR : 1.11 , 95 % CI : 0.78 to 1.58 ; p = 0.57 ) , or worsening HF [ HR : 0.62 , 95 % CI : 0.37 to 1.02 ; p = 0.059 ) . CONCLUSIONS A rhythm-control strategy or the presence of sinus rhythm are not associated with better outcomes in patients with AF and CHF", "Background Recent studies of patients with heart failure and of patients receiving intensive care indicate that digoxin may increase mortality if the patient has atrial fibrillation ( AF ) . Objective To study which patients receive digoxin treatment for AF and what the prognosis is for patients given this treatment . Method 2824 patients with AF were studied prospect ively for a mean of 4.6 years . Information about medication was obtained from the local hospital registry . Information about diagnoses , hospitalisations and deaths was obtained from national registries . Propensity score matching and Cox regression was used to account for confounding . Results Factors associated with digoxin use were permanent AF ( hazard ratio ( HR ) = 3.2 , confidence interval ( CI ) 2.7 to 3.9 ) , absence of pacemaker ( HR = 2.3 , CI 1.6 to 3.2 ) , history of heart failure ( HR = 2.0 , CI 1.7 to 2.5 ) , treatment in an internal medicine ward rather than a cardiology ward ( HR = 1.6 , CI 1.3 to 2.0 ) , female sex ( HR = 1.6 , CI 1.3 to 1.9 ) and age ≥80 years ( HR = 1.4 , CI 1.1 to 1.7 ) . More patients with than without digoxin died ( 51 % vs 31 % , p digoxin use could be found for all-cause mortality , myocardial infa rct ion , ischaemic stroke , time to readmission to hospital or days at hospital/year at risk . The only end point significantly associated with digoxin use was pacemaker implantations , which were more common in digoxin-treated patients ( HR = 2.0 , CI 1.2 to 3.4 ) . Conclusion Digoxin is mainly given to an elderly and frailer subset of patients with AF and is thus associated with an increased mortality . When differences in patient characteristics are accounted for digoxin use seems to have a neutral effect on mortality and major cardiovascular events in patients with AF", "BACKGROUND Atrial fibrillation occurs frequently in patients with congestive heart failure and commonly results in clinical deterioration and hospitalization . Sinus rhythm may be maintained with antiarrhythmic drugs , but some of these drugs increase the risk of death . METHODS We studied 1518 patients with symptomatic congestive heart failure and severe left ventricular dysfunction at 34 Danish hospitals . We r and omly assigned 762 patients to receive dofetilide , a novel class III antiarrhythmic agent , and 756 to receive placebo in a double-blind study . Treatment was initiated in the hospital and included three days of cardiac monitoring and dose adjustment . The primary end point was death from any cause . RESULTS During a median follow-up of 18 months , 311 patients in the dofetilide group ( 41 percent ) and 317 patients in the placebo group ( 42 percent ) died ( hazard ratio , 0.95 ; 95 percent confidence interval , 0.81 to 1.11 ) . Treatment with dofetilide significantly reduced the risk of hospitalization for worsening congestive heart failure ( risk ratio , 0.75 ; 95 percent confidence interval , 0.63 to 0.89 ) . Dofetilide was effective in converting atrial fibrillation to sinus rhythm . After one month , 22 of 190 patients with atrial fibrillation at base line ( 12 percent ) had sinus rhythm restored with dofetilide , as compared with only 3 of 201 patients ( 1 percent ) given placebo . Once sinus rhythm was restored , dofetilide was significantly more effective than placebo in maintaining sinus rhythm ( hazard ratio for the recurrence of atrial fibrillation , 0.35 ; 95 percent confidence interval , 0.22 to 0.57 ; P torsade de pointes in the dofetilide group ( 3.3 percent ) as compared with none in the placebo group . CONCLUSIONS In patients with congestive heart failure and reduced left ventricular function , dofetilide was effective in converting atrial fibrillation , preventing its recurrence , and reducing the risk of hospitalization for worsening heart failure . Dofetilide had no effect on mortality", "Because conventional antiarrhythmic therapy is often ineffective in maintaining sinus rhythm or is associated with adverse side effects in patients with atrial fibrillation ( AF ) , there is a clinical need to test newer agents . One hundred patients with AF who had unsuccessful therapy with 1.9 + /- 1.0 type IA antiarrhythmic agents were r and omized to receive either propafenone ( n = 50 ) or sotalol ( n = 50 ) . Patients were stratified into 4 groups based on AF pattern ( chronic vs paroxysmal ) and left atrial size ( large [ > or = 4.5 cm ] vs small [ proportion of patients remaining in sinus rhythm on each agent was calculated for each group by the Kaplan-Meier method . For patients r and omized to propafenone , 46 + /- 8 % , 41 + /- 8 % and 30 + /- 8 % remained in sinus rhythm at 3 , 6 and 12 months , respectively , after cardioversion . A similar proportion of patients treated with sotalol remained in sinus rhythm at follow-up ( 49 + /- 7 % , 46 + /- 8 % and 37 + /- 8 % at 3 , 6 and 12 months , respectively ; p = NS ) . The proportion of patients remaining in sinus rhythm on propafenone and sotalol was not dependent on arrhythmia pattern or left atrial dimension . Except for constipation that occurred more frequently in patients treated with propafenone , adverse side effects were equally distributed between the 2 therapies . Two patients receiving sotalol died during follow-up . Propafenone and sotalol , 2 new antiarrhythmic agents , were found to be equally effective in maintaining sinus rhythm in 100 patients with recurrent AF . Response rates were not affected by arrhythmia pattern , left atrial size or unsuccessful prior drug therapy . ( ABSTRACT TRUNCATED AT 250 WORDS", "INTRODUCTION . Atrial fibrillation is a frequent cause of worsening of symptoms in patients with congestive heart failure . The drugs currently available for maintenance of sinus rhythm all have major side effects . METHODS . In 34 Danish coronary care units , 1518 patients with congestive heart failure and reduced left ventricular systolic function were r and omized to receive either placebo or a new class III antiarrhythmic drug , dofetilide . The dose of dofetilide was adjusted according to the presence of atrial fibrillation , the length of the QT interval , and renal function . Patients were continuously monitored electrocardiographically for the first 3 days of the study . The primary end point was all-cause mortality and follow-up was for at least 1 year . RESULTS . In the dofetilide/placebo groups , 311/317 patients died ( 41%/42 % ) . The hazard ratio for dofetilide treatment was 0.95 ( 95 % confidence interval , 0.81 - 1.11 ) . Treatment with dofetilide reduced worsening of heart failure significantly ( hazard ratio , 0.75 ; 0.63 - 0.89 ) . After 1 year , 61 % of patients with atrial fibrillation at the start of the study had converted to sinus rhythm on dofetilide , vs. 33 % in the placebo group . After conversion to sinus rhythm , 78%/43 % of patients in the dofetilide/placebo groups remained in sinus rhythm for at least 1 year . There were 25 instances ( 3 % ) of torsade de pointes ventricular tachycardia in the dofetilide group and none in the placebo group . CONCLUSION . In patients with congestive heart failure , dofetilide can effectively convert atrial fibrillation to sinus rhythm and maintain sinus rhythm after conversion . Hospitalization for congestive heart failure is reduced . Dofetilide does not affect mortality . (c)2001 by CHF ,", "Epidemiological , experimental studies and post hoc analyses of r and omized trials suggested that n-3 polyunsaturated fatty acids ( PUFA ) and statins could be beneficial in chronic heart failure . Two double-blind , placebo-controlled , r and omized clinical trials investigated the efficacy and safety of n-3 PUFA 1 g daily ( R1 ) and rosuvastatin 10 mg daily ( R2 ) in patients with heart failure . In total , 6975 and 4574 patients were r and omized in R1 and R2 , respectively ; the main reason for excluding patients from R2 being the open-label administration of statin treatment . Primary end points were death , and death or admission to hospital for cardiovascular reasons . n-3 PUFA , but not rosuvastatin , significantly decreased the two co primary end points : 56 and 44 patients needed to be treated with n-3 PUFA for a median duration of 3.9 years to avoid one death or one cumulative event . Both drugs were safe and were tolerated . A simple and safe treatment with n-3 PUFA provides a beneficial advantage in patients with heart failure in a context of usual care" ]	41189032-06ff-11f0-808a-c43d1ab1c353
The purpose of this systematic review was to determine the quality of the research and to assess the reliability of different types of physical examination procedures used in the assessment of patients with non-specific low back pain . A search of electronic data bases ( MEDLINE , PEDro , AMED , EMBASE , Cochrane , and CINAHL ) up to August 2005 identified 48 relevant studies which were analysed for quality and reliability . Pre-established criteria were used to judge the quality of the studies and satisfactory reliability , and conclusions emphasised high quality studies ( > or = 60 % methods score ) . The mean quality score of the studies was 52 % ( range 0 to 88 % ) , indicating weak to moderate methodology . Based on the upper threshold used ( kappa/ICC > 0.85 ) most procedures demonstrated either conflicting evidence or moderate to strong evidence of low reliability . When the lower threshold was used ( kappa/ICC > 0.70 ) evidence about pain response to repeated movements changed from contradictory to moderate evidence for high reliability . Most procedures commonly used by clinicians in the examination of patients with back pain demonstrate low reliability	[ "The interexaminer reliability of noninvasive methods of examining lumbar spinal segments is not well established . In this project the interexaminer reliability of three experienced chiropractic examiners , who evaluated 21 symptomatic and 25 asymptomatic subjects , was explored . Eight noninvasive segmental examination strategies ( dimensions ) were employed at each spinal segment from T11/T12 through L5/S1 . Marginal to good agreement beyond chance was noted for palpatory pain over osseous structures and in paraspinal soft-tissues . Weaker and less frequently , significant concordance between examiners was noted for detection of temperature differences ( greater than or equal to 1.5 degrees F ) between adjacent segments and for visual inspection for segmental abnormality . Little significant agreement between examiner was found for active and passive motion palpation , muscle tension palpation and misalignment palpation . This study suggests that \" subjective \" findings ( pain ) may be among the most reliable of conservative spinal observations . Weak but significant correlations were found when positive findings for the eight dimensions at each lumbar segment were summed to form a composite joint abnormality index . When the multidimension index was developed using the four most reliable dimensions , slightly stronger correlations were found . The strongest agreement between examiners tended to be found in the lower lumbar spine", "Study Design This prospect i ve study evaluated the diagnostic utility of historically accepted sacroiliac joint tests . A multidisciplinary expert panel recommended 12 of the “ best ” sacroiliac joint tests to be evaluated against a criterion st and ard of unequivocal pain relief after an intra‐articular injection of local anesthetic into the sacroiliac joint . Objectives To identify a single sacroiliac joint test or ensemble of tests that are sufficiently useful in diagnosing sacroiliac joint disorders to be clinical ly valuable . Summary of Background Data No previous research has been done to evaluate any physical test of sacroiliac joint pain against an accepted criterion st and ard . Methods Historical data was obtained , and the 12 tests were performed by two examiners on 85 patients who subsequently underwent sacroiliac joint blocks . Ninety percent or more relief was considered a positive response , and less then 90 % relief was considered a negative response . Results There were 45 positive and 40 negative responses . No historical feature , none of the 12 sacroiliac joint tests , and no ensemble of these 12 tests demonstrated worthwhile diagnostic value . Conclusion Sacroiliac joint pain is resistant to identification by the historical and physical examination data from tests evaluated in this study", "Study Design . Cohort study of patients with acute low back pain undergoing physical therapy . Objectives . Examine the reliability and validity of the Physical Impairment Index in a group of patients with acute low back pain and determine the responsiveness and minimum detectable change of the index and its component tests . Summary of the Background Data . The Physical Impairment Index was originally described as a reliable and valid means of assessing physical impairment in patients with low back pain . The psychometric properties of the index have not been reported in patients with acute low back pain , nor has its responsiveness been examined . Methods . Seventy-eight patients with acute ( were assessed at baseline and after 4 weeks . Interrater reliability of the index was examined in a subgroup of 20 patients . Validity was examined through correlations with concurrent measures of pain , disability , and psychosocial variables . Changes in the index over 4 weeks were used to assess responsiveness and minimum detectable change . Results . Interrater reliability of the index was high ( intraclass correlation coefficient = 0.89 ) , and its validity was generally supported by the pattern of correlations . The index was more responsive to change than any of its component tests but was less responsive than the Oswestry disability score . The minimum detectable change on the index was approximately 1 point . Conclusions . The Physical Impairment Index appears to be a reliable and valid measure of physical impairment for patients with acute low back pain and may be useful as an adjunct outcome measure for studies involving these patients . Further research on patients with chronic pain is needed before it can be advocated for outcomes research with this population", "Sixty student volunteers were assessed for fixation in the lumbar spine using a passive motion palpation protocol . Subjects were examined in r and om order by two experienced chiropractors . Every subject was evaluated twice by each examiner . Fixations were judged present or absent for each of five lumbar motion segments . Moderate test-retest agreement beyond chance was noted at L1/2 , minimal reliability at L4/5 , and no significant agreement within examiners was detected for mid-lumbar segments . Interexaminer agreement beyond chance was poor for all segments assessed . When segments were grouped regionally and re-evaluated , some increase in intrarater agreement was evident , especially at L4/5/S , but interrater agreement was still absent", "STUDY DESIGN A prospect i ve method ological interrater reliability study . OBJECTIVES To calculate the interrater reliability among clinicians newly trained in a classification system for acute low back pain and to determine the level of agreement at key junctures within the classification algorithm . BACKGROUND The utility of a classification system for patients with low back pain depends on its reliability and generalizability . To be practical , clinicians must be able to apply the system after a reasonable amount of training . Identifying key points in the classification algorithm where disagreement occurs can lead to better operational definitions . METHODS Four physical therapists read an article and attended a 1-day training session in the classification system . R and omly paired therapists classified patients referred for treatment of acute low back pain and noted decisions at key junctures in the system algorithm . RESULTS Forty-five patients were classified . Repeated examinations did not increase the patient 's pain ( P>.05 ) . For 3 out of the 4 therapists , the interrater reliability showed a kappa value of 0.45 . The fourth therapist , excluded from the overall analysis , exhibited a bias towards the immobilization classification . Among the 3 therapists , major disagreement occurred with the determination of symmetry with trunk side bending and the effects of repeated movements . CONCLUSIONS Three out of 4 clinicians newly trained in the system showed moderate reliability . The reliability was slight when the fourth therapist was included . Refinement of the operational definitions and criteria for determining lumbar capsular patterns are needed . One day of training is probably not adequate for all therapists , especially for those biased towards specific low back pain syndromes", "BACKGROUND AND PURPOSE McKenzie described a two-step process for assessing patients with low back pain for a lateral shift . The purpose of this study was to determine whether reliable judgments about lateral shifts could be obtained . SUBJECTS Forty-nine patients with low back pain were each examined separately by two r and omly paired physical therapists . METHODS Assessment s of the presence and direction of lateral shifts ( step 1 ) were obtained by use of a simple instrument . The relevance of the lateral shifts to the patients ' pain complaints ( step 1 ) also was assessed by use of the side-glide test sequence . RESULTS Generalized kappa coefficients were calculated to determine reliability . The kappa value for the two-step process of lateral shift assessment was .16 . The percentage of agreement was 47 % . CONCLUSION AND DISCUSSION Each step in this two-step process was examined separately for possible sources of error . The kappa value for determinations of the presence and direction of lateral shifts was .00 , indicating very poor reliability . The kappa value for the determination of the presence of a positive side-glide test sequence was .74 , indicating high reliability . The role of lateral shift assessment in the McKenzie system should be reconsidered , given the strong research evidence for poor reliability of determinations of the presence and direction of lateral shifts", "The purpose of this study was to determine the intertester reliability of assessment s of the presence of trigger points in the region of the lumbar spine of patients with low back pain ( LBP ) . A total of six trigger points described by Travell and Simons were studied . The trigger point examination procedures described by Travell and Simons were used by 12 physical therapists . R and omly paired therapists examined 50 patients for 197 trigger points . The Kappa coefficient , percent agreement , the observed proportion of positive agreement ( Ppos ) , and the observed proportion of negative agreement ( Pneg ) were used to describe reliability . Kappa values ranged from .29 to .38 . Percent agreement ranged from 76 % to 79 % . Ppos ranged from .43 to .52 . The low Kappa and Ppos values suggest different therapists are unable to reliably determine when a trigger point is present in a patient with LBP . This study suggests the usefulness of examining for the presence of trigger points in patients with LBP should be question ed", "The presence of a trigger point is essential to the myofascial pain syndrome . This study centres on identifying clearer criteria for the presence of trigger points in the quadratus lumborum and gluteus medius muscle by investigating the occurrence and inter-rater reliability of trigger point symptoms . Using the symptoms and signs as described by Simons ' 1990 definition and two other former sets of criteria , 61 non-specific low back pain patients and 63 controls were examined in general practice by 5 observers , working in pairs . From the two major criteria of Simons ' 1990 definition only ' localized tenderness ' has good discriminative ability and inter-rater reliability ( kappa > 0.5 ) . This study does not find proof for the clinical usefulness of ' referred pain ' , which has neither of these two abilities . The criteria ' jump sign ' and ' recognition ' , on the condition that localized tenderness is present , also have good discriminative ability and inter-rater reliability . Trigger points defined by the criteria found eligible in this study allow significant distinction between non-specific low back pain patients and controls . This is not the case with trigger points defined by Simons ' 1990 criteria . Concerning reliability there is also a significant difference between the two different criteria sets . This study suggests that the clinical usefulness of trigger points is increased when localized tenderness and the presence of either jump sign or patient 's recognition of his pain complaint are used as criteria for the presence of trigger points in the M. quadratus lumborum and the M. gluteus medius", "BACKGROUND AND PURPOSE The purpose of this study was to examine the interrater reliability of measurements obtained by examiners administering tests proposed to be important for classifying low back pain ( LBP ) problems . SUBJECTS Ninety-five subjects with LBP ( 41 men , 54 women ) and 43 subjects without LBP ( 17 men , 26 women ) were examined by 5 therapists trained in the techniques used . METHODS A manual was developed by the first author that described the clinical examination procedures . The therapists were trained by the first author in the test procedures and definitions . The training included instruction through videotapes , practice and a written examination . Each examination was conducted by a pair of therapists . Within a pair , a therapist was the primary examiner for half of the subjects and an observer was the primary examiner for half of the subjects . Examination findings were recorded independently , without discussion . RESULTS Percentage of agreement and generalized kappa coefficients were used to analyzed the data . Kappa values were > or = .75 for all 28 items related to the symptoms elicited and > or = .40 for 72 % of the 25 items related to alignment and movement . CONCLUSION AND DISCUSSION The results suggest that experienced therapist who had trained together were able to agree on the results of examinations and obtain an acceptable level of reliability . Future work should focus on testing of reliability when more than one therapist performs the examination and when therapist not trained by the test developer to administer the examination perform the tests . [ Van Dillen LR , Sahrmann SA , Norton BJ , et al. Reliability of physical examination items used for classification of patients with low back pain", "Study Design . A test – retest design was used . Objective . To assess interexaminer reliability of the McKenzie method for performing clinical tests and classifying patients with low back pain . Summary of Background Data . Clinical methods and tests classifying patients with nonspecific low back pain have been based mainly on symptom duration or extent of pain referral . The McKenzie mechanical diagnostic and classification approach is a widely used noninvasive , low-technology method of assessing patients with low back pain . However , little is known about the interexaminer reliability of the method , previous studies having yielded conflicting results . Methods . For this study , 39 volunteers with low back pain , mean age 40 years ( range , 24–55 years ) , were blindly assessed by two physical therapists trained in the McKenzie method . The variability of two examiners for binary decisions was expressed by the kappa coefficient , and by the proportion of observed agreement , as calculated from a 2 × 2 contingency table of concordance . Results . On the basis of pure observation alone , agreement among clinical tests on the presence and direction of lateral shift was 77 % ( & kgr ; = 0.2;P Agreement on the relevance of lateral shift and the lateral component according to symptom responses was 85 % ( & kgr ; = 0.7;P McKenzie lumbar spine assessment in performing clinical tests and classifying patients with low back pain into syndromes were good and statistically significant when the examiners had been trained in the McKenzie method", "STUDY DESIGN This prospect i ve study of intertester reliability examined pairs of therapists ' ability to agree independently on a patient 's low back pain diagnosis . OBJECTIVE To determine the intertester reliability of a low back pain classification system among experienced and novice clinicians . BACKGROUND Many of the disparate categorization schemes for patients with low back pain are purely nominal , assigning design ations based on the presumptive source of the problem without providing any practical guide for rehabilitation . A useful classification scheme reliably groups patients into treatment-directing categories . METHODS The study included 204 patients with low back pain referred to 10 clinics across Canada . Paired physiotherapists performed separate physical examinations on each patient . Both examiners then completed a simple ballot choosing one of five pain patterns . RESULTS Agreement on patient classification by independent examiners was 78.9 % ( kappa = 0.61 ) . CONCLUSION This clinical ly relevant and clearly defined pain pattern system uses key elements of the history and examination to classify patients with low back pain . The pattern provides a framework for initiating active rehabilitation strategy . Using this approach , clinicians agreed on the categorization of 78.9 % of mechanical low back pain cases", "STUDY DESIGN Prospect i ve intertester reliability study investigating the ability of 2 therapists to agree on a low back pain diagnosis using examination techniques and the classification system described by McKenzie . OBJECTIVES To investigate intertester agreement in determining McKenzie diagnostic syndromes , subsyndromes , presence , and relevance of the spinal deformities . BACKGROUND Reliability of the McKenzie approach for determining diagnostic categories is unclear . Previous studies have been characterized by inconsistency of test protocol s , criterion measures , and level of training of the examiners , which confounds the interpretation of results . METHODS Patients were assessed simultaneously by 2 physical therapists trained in the McKenzie evaluation system . The therapists were r and omly assigned as examiner and observer . Agreement was estimated by Kappa statistics . RESULTS Forty-five subjects ( 47 + /- 14 years ) , composed of 25 women and 20 men with acute , subacute , or chronic low back pain were examined . The agreement between raters for selection of the McKenzie syndromes was kappa = 0.70 , and for the derangement subsyndromes was kappa = 0.96 . Interrater agreement for presence of lateral shift , relevance of lateral shift , relevance of lateral component , and deformity in sagittal plane was kappa = 0.52 , 0.85 , 0.95 , and 1.00 , respectively . Intertester agreement on syndrome categories in 17 patients under 55 years of age was excellent , with kapp = 1.00 . CONCLUSIONS A form of low back evaluation , using patterns of pain response to repeated end range spinal test movements , was highly reliable when performed by 2 properly trained physical therapists", "The McKenzie system for examining and treating patients with low back pain is frequently used by clinicians . The primary purpose of this multicenter study was the determine the intertester reliability of assessment s of patients with low back pain when physical therapists used the McKenzie method . A second purpose was to determine if previous postgraduate training in the McKenzie system affects reliability . Some therapists had previously undertaken postgraduate training in the McKenzie system . All therapists were given written descriptions of the McKenzie method and the criteria used to classify patients , Classifications were made on 363 patients with low back pain by r and omly paired physical therapists in eight clinics . The Kappa value on agreement of patient classification was 0.26 , which suggests poor reliability . Therapists agreed on which syndrome was present 39 % of the time . Previous postgraduate training did not reliability . The results suggest that assessment s of the syndrome present in patients ; with low back pain appear to be unreliable when using the McKenzie system", "Study Design . A prospect i ve , consecutive , cohort study of patients with acute low back pain classified into subgroups based on examination data and treated with a specific treatment approach . Objective . To calculate the interrater reliability of a classification system , and to compare initial patient characteristics and outcomes of physical therapy treatment when a classification approach is used . Summary of Background Data . Classification of patients with low back pain into homogeneous subgroups has been identified as a research priority . Identifying relevant subgroups of patients could improve clinical outcomes and research efficiency . Methods . Consecutive patients referred to physical therapy for treatment of acute low back pain were evaluated and classified into one of four subgroups ( immobilization , mobilization , specific exercise , or traction ) before treatment . Physical therapy treatment was based on the patient ’s classification . The classifications were compared for initial patient characteristics , frequency and duration of physical therapy , and improvement in Oswestry scores . Results . In this study , 120 patients were evaluated and classified . Analysis of interrater reliability showed a kappa value of 0.56 . Differences were found among the classifications for age , initial Oswestry score , history of low back pain , symptom distribution , and average change in Oswestry score with treatment . Conclusions . Reaching a consensus regarding relevant patient subgroups requires data on the reliability and validity of existing classification systems . Further work is required to vali date improvement in treatment outcomes using a classification approach", "OBJECTIVE To assess the intraexaminer and interexaminer reliability of clinicians trained in flexion-distraction technique to determine the need for chiropractic adjustment of each segment of the lumbar spine . DESIGN This was an intraexaminer and interexaminer reliability study of commonly used chiropractic assessment procedures , including static and motion palpation and visual observation . SETTING Chiropractic college ; by four licensed chiropractors trained in flexion-distraction technique , two with more than 20 years ' experience and two with 3 or fewer years ' experience . SUBJECTS Subjects were 18 volunteers ; 16 were symptom free , and 2 had low back pain at the time the study was conducted . MAIN OUTCOME MEASURE The kappa statistic was computed for all comparisons and interpreted in categories ranging from \" poor \" ( 0.80 ) . RESULTS Intraexaminer reliability was greater than interexaminer reliability . For intraexaminer reliability there was considerable variation by segment and among the four examiners , but intraexaminer reliability appeared generally higher than interexaminer reliability . Overall , more subluxations were identified on the second examination than on the first . For interexaminer reliability , kappa scores were generally in the \" poor \" to \" slight \" categories . DISCUSSION The results of this study , similar to those of other studies , indicate that even chiropractors trained in the same technique seem to show little consensus on the indications for the necessity to adjust specific segments of the spine . A more st and ardized assessment approach might be helpful in improving the reliability of diagnostic assessment", "BACKGROUND CONTEXT Research has demonstrated some progress in using a clinical examination to predict discogenic or sacroiliac ( SI ) joint sources of pain . No clear predictors of symptomatic lumbar zygapophysial joints have yet been demonstrated . PURPOSE To identify significant components of a clinical examination that are associated with symptomatic lumbar discs , zygapophysial joints and SI joints . STUDY DESIGN A prospect i ve , criterion-related concurrent validity study performed at a private radiology practice specializing in spinal diagnostics . PATIENT SAMPLE The sample consisted of 81 patients with chronic lumbopelvic pain referred for diagnostic injections . OUTCOME MEASURES Contingency tables were constructed for nine features of the clinical evaluation compared with the results of diagnostic injections . Statistical analysis included chi-squared test for independence , phi and odds ratios with confidence intervals . METHOD Patients received blinded clinical examinations by physical therapists , and diagnostic injections were used as the criterion st and ard . RESULTS Significant relationships were found between discogenic pain and central ization of pain during repeated movement testing , and pain when rising from sitting . Lumbar zygapophysial joint pain was associated with absence of pain when rising from sitting . Sacroiliac joint pain was related to three or more positive pain provocation tests , pain when rising from sitting , unilateral pain and absence of lumbar pain . CONCLUSIONS Significant correlations exist between clinical examination findings and symptomatic lumbar discs , zygapophysial and SI joints . The strongest relationships were seen between SI joint pain and three or more positive pain provocation tests , central ization of pain for symptomatic discs and absence of pain when rising from sitting for symptomatic lumbar zygapophysial joints", "Palpating a nominated spinal level is a prerequisite to more complex tasks such as palpating the level most likely to be the source of the patient 's symptoms . The aim of this study was to investigate the reliability of physiotherapists with a post-graduate qualification in manipulation ( manipulative physiotherapists ) in palpating the lumbar spines of patients in a clinical setting . Three pairs of manipulative physiotherapists palpated the r and omly-nominated lumbar spinal levels of 20 patients presenting to their practice s for treatment of low-back pain . Each therapist marked the skin overlying the spinous process of the nominated spinal level with an ultraviolet pen and these marks were transcribed onto transparencies for analysis . The therapists obtained an overall weighted kappa of 0.92 indicating almost perfect agreement for locating the nominated spinal level . The results of this study indicate that manipulative physiotherapists can reliably palpate nominated lumbar spinal levels , suggesting further training in spinal therapy enhances the palpatory skills of physiotherapists in palpating nominated lumbar spinal levels" ]	4118906e-06ff-11f0-808a-c43d1ab1c353
INTRODUCTION Adhesion formation is the most common complication following peritoneal surgery and the leading cause of small bowel obstruction , acquired infertility and inadvertent organ injury at reoperation . Using a ' good surgical technique ' is advocated as a first step in preventing adhesions . However , the evidence for different surgical techniques to reduce adhesion formation needs confirmation . METHODS Pubmed , Embase and CENTRAL were search ed to identify r and omized controlled trials that investigated the effect of various aspects of surgical technique on adhesion-related outcomes . Clinical outcomes and incidence of adhesions were the primary endpoints . Identification of papers and data extraction were performed by two independent research ers . RESULTS There were 28 papers with 27 studies included for a systematic review . Of these , 17 studies were eligible for meta- analysis and 11 for qualitative assessment only . None of the techniques that were compared significantly reduced the incidence of adhesive small bowel obstruction . In a small low- quality trial , the pregnancy rate increased after subserous fixation of suture knots . However , the incidence of adhesions was lower after laparoscopic compared with open surgery [ relative risk ( RR ) 0.14 ; 95 % confidence interval ( CI ) : 0.03 - 0.61 ] and when the peritoneum was not closed ( RR 0.36 ; 95 % CI : 0.21 - 0.63 ) . CONCLUSIONS None of the specific techniques that were compared reduced the two main adhesion-related clinical outcomes , small bowel obstruction and infertility . The meta- analysis provides little evidence for the surgical principle that using less invasive techniques , introducing less foreign bodies or causing less ischaemia reduces the extent and severity of adhesions	[ "Laparoscopic Nd-YAG laser photocoagulation of the ovaries was performed in 40 anovulatory women with clomiphene citrate-resistant polycystic ovary disease . Following this procedure , the subjects were r and omly assigned to have either a second-look laparoscopy with lysis of adhesions within 3 - 4 weeks of the initial laparoscopy ( N=19 ) or expectant management ( N=20 ) . One patient assigned to the laparoscopy group refused the procedure . Minimal and mild adhesions that did not distort the normal tubo-ovarian relationship were encountered in 13 patients ( 68 % ) in the second-look laparoscopy group ; these adhesions were easily lysed using sharp or blunt dissection . The pregnancy rates over 6 months were similar in the two groups ( 47 % in the second-look group and 55 % in the expectant-management group ; P>.05 ) . These data suggest that early laparoscopic lysis of adhesions does not improve short-term conception rates following laparoscopic Nd-YAG laser photocoagulation of polycystic ovaries", "This study describes a prospect i ve r and omized controlled trial to evaluate whether suture of the peritoneal layer is necessary as a separate step in the closure of midline abdominal surgical wounds . Consecutive patients undergoing abdominal operation — elective and emergency surgery — through a midline abdominal wound were r and omized to have the peritoneal layer closed with continuous catgut , or to have this step omitted . The linea alba was closed with interrupted stainless steel sutures , and the skin approximated with staples . Patients were evaluated for wound sepsis , wound dehiscence , and subsequent incisional hernia development . Postoperative pain was assessed by a self-administered visual analogue score , and by measuring narcotic requirements . There was no significant difference in narcotic requirements , pain scores , or wound complications between the 2 groups . Single-layer closure of the abdominal wall is quicker , less costly , and theoretically safer than layered closure , and it is recommended that separate suture of the peritoneum be ab and oned . ResuméDans cette étude prospect i ve , r and omisée , et contrôlée , nous avons cherché à savoir si la fermeture individualisée du péritoine était nécessaire dans la fermeture d'une laparotomie médiane . Deux cents patients consécutifs — opérés à froid ou en urgence — par laparotomie médiane , ont été r and omisés : dans un groupe , le péritoine a été fermé en un plan individualisé par un surjet au catgut , dans l'autre , le péritoine n'a pas été suturé . La ligne blanche a été fermée en un plan par des points séparés de fils d'acier ; la peau a été fermée par des agrafes . On a étudié le nombre des abcès de paroi , des éviscérations , et , à distance , des éventrations . La douleur postopératoire a été évaluée par un score analogue visuel , établi par le patient lui-même , ainsi que par la nécessité d'utiliser des antalgiques . Il n'y avait pas de différence significative entre les 2 groupes en ce qui concerne le taux de complications pariétales ou l'existence de douleur . Comme la fermeture pariétale en un seul plan est plus rapide , coûte moins cher , et , est théoriquement plus sûre ( on peut surveiller le contenu intrapéritonéal pendant la fermeture ) que la fermeture plan par plan , nous recomm and ons d'ab and oner la fermeture individualisée du péritoine . ResumenEl presente articulo describe un ensayo clínico prospect ivo destinado a investigar si es necesaria la sutura de la capa peritoneal como un paso independiente en el cierre de incisiones abdominales de línea media . Una serie de pacientes consecutivos sometidos a operaciones abdominales fueron r and omizados a cierre peritoneal con sutura continua de catgut o a omisión de este paso . La línea alba fue cerrada con suturas interrumpidas de acero inoxidable y la piel con agrafes . Se estudió la incidencia de infección de herida , de dehiscencia , y de desarrollo de hernia incisional subsiguientes . La valoración del dolor postoperatorio fue realizada mediante autoevaluación con una escala linear análoga y la determinación de los requerimientos de narcóticos . No se encontraron diferencias significativas en el requerimiento de narcóticos para analgesia , en el nivel de la escala de dolor , o en la tasa de complicaciones entre los 2 grupos . El cierre de la pared abdominal en una capa única es más rápido , menos costoso , y teóricamente más seguro ; por lo tanto , se recomienda ab and onar la sutura del peritoneo", "OBJECTIVE To determine the effect of closure or non-closure of the visceral peritoneum at cesarean delivery on uterine scar formation assessed at repeat cesarean delivery . METHODS Women undergoing initial cesarean delivery were allocated into 2 groups : group 1 underwent visceral peritoneal closure , while in group 2 the visceral peritoneum was not closed . At repeat cesarean delivery 4 specimens from the initial uterine scar were collected and assessed by light microscopy and scanning electron microscopy . RESULTS In group 1 , 57 % of women had adhesions compared with 20.6 % in group 2 ( P reactive mesothelial hyperplasia ( 51.8 % vs 13.7 % ) , submesothelial fibrosis ( 48.1 % vs 6.8 % ) , and neoangiogenesis of mesothelial stroma ( 44.4 % vs 12 % ) in group 1 and group 2 patients , respectively ( P pericytes on the surface of microvessels in group 1 compared with group 2 ( 26.3+/-1.4 vs 11.5+/-1.1 patients ; P inflammatory reaction and adhesions , evidence d by reactive and regenerative mesothelial hyperplasia and submesothelial fibrosis", "Objectives Laparoscopic ovarian drilling ( LOD ) has been put forward as the treatment of choice in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome ( PCOS ) , with tubo-ovarian adhesion formation as the major disadvantage . Our study proposed to compare the efficacy of laparoscopic unilateral ovarian drilling with bilateral ovarian drilling in terms of ovulation and pregnancy rate with the expected advantage of decreasing postoperative adhesion rate and change in fimbiro ovarian relationship with unilateral drilling . Methods This prospect i ve r and omized study included 44 patients with anovulatory infertility due to PCOS . Twenty-two patients underwent unilateral ovarian drilling in group-I and 22 patients underwent bilateral ovarian drilling in group-II between June 2005 and June 2007 . The number of drilling site in each ovary was limited to five . The clinical and biochemical response , ovulation and pregnancy rates over a follow-up period of 1 year were compared . Tubo-ovarian adhesion rate was compared during cesarean section or during repeat laparoscopy . Results There was no statistical difference between the two groups in terms of clinical and biochemical response , ovulation rate and pregnancy rate . Postoperatively , tubo-ovarian adhesions could be assessed in 36.3 % of the patients and no adhesions were found in a single case in either group . Conclusion Unilateral drilling cauterization of ovary is equally efficacious as bilateral drilling in inducing ovulation and achieving pregnancy . Unilateral ovarian drilling may be a suitable option in clomiphene citrate resistant infertility patient of PCOS which can replace bilateral ovarian drilling with the potential advantage of decreasing the chances of adhesion formation", "BACKGROUND The purpose of this study was to analyze long-term recurrence rates and complications in patients previously enrolled in a prospect i ve r and omized trial comparing laparoscopic ( LC ) and open ileocolectomy ( OC ) for ileocolic Crohn 's disease ( CD ) . METHODS Follow-up data were available on 56 of 60 patients . Demographic data , recurrence rates , need for additional surgery related to primary procedure , and medication use were recorded . RESULTS Mean follow-up for 56 patients ( 27 LC vs 29 OC ) was 10.5 years and comparable between LC and OC ( 10.0 vs 11.0 , respectively ; P = .64 ) . One patient died 8 years after OC of causes unrelated to CD . Eight patients for each group underwent initial reoperative ( 26 % LC vs 28 % OC ; P = .89 ) . One patient underwent incisional hernia repair after LC ( 4 % ) versus 4 patients ( 14 % ) after OC ( P = .61 ) . Two patients in the LC group underwent adhesiolysis versus none after OC ( P = .23 ) . Incidences of anorectal disease , anorectal surgery , endoscopic or radiologic recurrence , and medication use were also similar between LC and OC . OC patients requiring operation during follow-up were significantly more likely than LC to require multiple operations ( P = .006 ) . CONCLUSIONS Long-term data from this prospect i ve r and omized trial confirm that LC is at least comparable to OC in the treatment of ileocolic CD", "OBJECTIVE To assess the rate of adhesions and other long-term outcomes of two cesarean delivery techniques . METHODS A total of 600 women were r and omly assigned to either a st and ard ( Pfannenstiel-Kerr ) or modified ( Joel-Cohen-Stark ) technique for first-time cesarean delivery . A total of 124 women were assessed at repeat cesarean delivery . The primary outcome measure was the presence of adhesions . RESULTS At repeat cesarean delivery , anesthesia-to-delivery time , total duration of surgery , change in hemoglobin level , time to mobilization and oral intake , and postoperative hospital stay were significantly less with the modified technique . Adhesions were found in 7 ( 11.3 % ) and 22 ( 35.5 % ) of the cases using the modified and st and ard techniques , respectively ( P=0.0026 ; relative risk 3.14 [ 95 % CI , 1.45 - 6.82 ] ) . CONCLUSION A modified cesarean delivery technique , including Joel-Cohen incision , exteriorized full thickness suturing of the uterine incision , and non-closure of the peritoneum may reduce long-term morbidities of the procedure", "OBJECTIVE To compare bipolar coagulation and suturing of the ovary in terms of postoperative ovarian adhesions after laparoscopic ovarian cystectomy for endometriosis . DESIGN Prospect i ve , r and omized , controlled study . SETTING Department of Obstetrics and Gynecology , University of Naples \" Federico II . \" PATIENT(S ) Thirty-two women with a single endometriotic cyst were r and omly divided into two groups of 16 women each ( groups A and B ) . INTERVENTION(S ) All patients underwent laparoscopic ovarian cystectomy for endometriosis . In group A , hemostasis was performed by closure of the ovary with an intraovarian suture . In group B , complete hemostasis was achieved only with bipolar coagulation on the internal face of the ovary . MAIN OUTCOME MEASURE(S ) Rate and extension of postsurgical ovarian adhesions at 60 - 90 days follow-up . RESULT ( S ) At follow-up , a significantly lower rate of postsurgical ovarian adhesions was observed in group A than in group B ( 30.8 % vs. 57.1 % ) . The extension of ovarian adhesions was significantly higher in group B than in group A. CONCLUSION ( S ) The use of sutures on ovaries treated for endometrioma is associated with a lower rate of postoperative ovarian adhesion formation compared with bipolar coagulation", " Thirty-four women with unruptured tubal ectopic pregnancy ( EP ) were r and omly assigned to undergo salpingotomy without tubal suturing ( n = 15 ) or salpingotomy with tubal suturing ( n = 19 ) . The reproductive performance of these patients was compared with 24 patients who underwent salpingectomy for their EP ( historical control ) . Using life table analysis , the cumulative probability of intrauterine pregnancy ( IUP ) at 12 and 24 months was 45 % and 45 % after salpingotomy without tubal suturing and 21 % and 47 % after salpingotomy with tubal suturing , respectively . The cumulative probability of IUP after salpingectomy ( 21 % and 26 % at 12 and 24 months , respectively ) was significantly lower than after salpingotomy with or without tubal suturing . There was no difference in the cumulative probability of EP after salpingotomy with or without tubal suturing , but it was significantly higher than after salpingectomy . In 18 women who subsequently underwent laparoscopy or laparotomy , no significant difference was found between the degree of adhesions after salpingotomy with or without tubal suturing . These findings suggest that IUP after conservative treatment is higher than after salpingectomy , but recurrent EP is also higher . Intrauterine pregnancy occurs earlier after salpingotomy without tubal suturing than after salpingotomy with tubal suturing . This might be because of rapid return of tubal function after healing by secondary intention", "BACKGROUND Adhesion b and s are reported to be among the most common complications of gynecological surgery procedures . The aim of this study was to compare the frequency of post-surgical adhesion among patients with closed or open peritoneal repair in the subsequent cesarean sections . METHODS A prospect i ve r and omized trial was performed on 45 patients who underwent cesarean section during a 5-year period . Among these patients , 24 patients were operated on by closure of the peritoneum and 21 patients were operated on by the non-closure method . Overall , 31 patients had a second pregnancy and cesarean section within the time of the study . These patients were evaluated to determine if they had any adhesion between the omentum and abdominal wall or uterus or between the uterus and abdominal wall or rectus muscle . RESULTS The two groups were similar to each other with regard to the causes of cesarean section . Seven cases of adhesions were diagnosed during subsequent cesarean sections among 13 patients ( 54 % ) with peritoneal non-closure , compared with 3 in 18 women ( 15 % ) with peritoneal closure ( relative risk : 3.2 ; 95 % confidence interval : 1.0 - 10.2 ) . CONCLUSION Closure of the peritoneum increases the operating time , but may decrease the risk of adhesions . The results of this study suggest that , during cesarean section , suture of the peritoneum may be a better option than leaving it unsutured", "The lateral paramedian incision has been advocated as the strongest incision for abdominal surgery . We have evaluated this incision and tested the necessity for closing the deep peritoneal layer by a prospect i ve r and omized trial . All 206 patients undergoing laparotomy in the Surgical Unit in 1984 , both elective and emergency cases , were included . In patients undergoing laparotomy through unscarred tissue , a lateral paramedian incision was performed and they were r and omized to have either the peritoneum closed ( n = 77 ) or left open ( n = 75 ) . Patients in whom the laparotomy was performed through a previous incision ( n = 51 ) and those in whom the abdomen had to be opened urgently ( n =3 ) were excluded from the trial but studied separately ( n = 54 ) . The rectus sheath was closed with monofilament nylon in all cases . Patients were assessed for wound integrity during the immediate postoperative period and at 1 , 3 , 6 and 12 months after operation . So far the patients have been followed up for between 1 and 2 years and follow‐up is continuing as in some cases incisional hernia may not be detected until several years after operation . There have been no cases of burst abdomen . No incisional hernias have developed in patients in whom a lateral paramedian incision was performed and the peritoneum was closed , and one incisional hernia has occurred in the patients in whom the peritoneum was left open . Seven incisional hernias have occurred in patients excluded from the trial of the lateral paramedian incision ( 13 per cent ) . We conclude that the lateral paramedian incision successfully abolishes the burst abdomen and that incisional hernia is rare . It is not necessary to close the peritoneum with this incision", "Background The management of small intestinal serosal defects remains controversial . Non-closure of such defects is regarded as a risk factor of fistula formation or intestinal leakage , whereas defect closure with absorbable suture material is potentially associated with adhesion formation . The aim of our pilot study was to evaluate the influence of small intestinal serosal defect closure on peritoneal wound healing , leakage rate , and adhesion formation in a rabbit model . Methods Twenty-two male rabbits were r and omized into two groups . Following median laparotomy , a st and ardized small intestinal serosal defect with a diameter of 1 cm was performed . Either the defect was closed by two seromuscular 4/0 polyglactin single sutures ( n = 11 ) or the defect was left open ( n = 11 ) . On postoperative day 14 , all animals were sacrificed for morphological investigations . Complications and the rate of intestinal leakage were measured . The degree of adhesion formation was measured by computer-assisted planimetry . Results No animal developed fistula formation or intestinal leakage . Eight ( 73 % ) animals of the closure group developed local peritoneal adhesions with a mean size of 39.7 ± 45 mm2 . No animal in the non-closure group revealed local peritoneal adhesions at the defect . However , two ( 18 % ) animals in the non-closure group developed peritoneal adhesions distant to the defect with a mean size of 3.5 ± 9 mm2 . Comparing both groups , the size of peritoneal adhesions was significantly higher in the closure group ( p = 0.013 ) . Conclusions Closure of isolated serosal injuries with resorbable suture material was associated with an adhesion formation in distressing certainty , whereas no leakage or fistula formation could be observed at all . Further studies are needed to clarify the impact of serosal defect closure in particular on leakage rate and fistula formation , e.g. , with pre-existing adhesions , in case of multiple serosal injuries or with a pre-existing peritonitis", "Laparoscopic adhesiolysis for chronic abdominal pain is subject for criticism . In this prospect i ve study , we analyze factors that encourage or discourage the indication for therapeutic laparoscopic adhesiolysis . Two hundred twenty-four consecutive patients with chronic abdominal pain underwent diagnostic laparoscopy , and in case of adhesions , they underwent adhesiolysis . Pain relief was assessed , and the individual impact of variables on pain relief was determined . Laparoscopy was performed in 224 patients . Two hundred patients had only adhesions and underwent primary laparoscopic adhesiolysis . Three months after adhesiolysis , 74 % of patients were pain-free or had less pain . The remaining 26 % of the patients felt no change ( 22 % ) or had more pain ( 4 % ) . Gender , age , and bowel perforation leading to a laparotomy appear to be individual factors significantly influencing pain relief . Laparoscopic adhesiolysis can be done ( almost ) completely in 92 % of patients with adhesions . After laparoscopic adhesiolysis , 74 % of patients had good results and 4 % had more pain . The complication rate is high", "Fifty six patients with typhoid enteric perforation who underwent operative treatment were r and omly assigned to 2 groups . Twenty seven patients in group A underwent laparotomy via the Rutherford-Morrison incision while 29 patients in group B underwent the same procedure via a right paramedian incision . Surgical treatment consisted of two layer closure of the perforation with peritoneal lavage and tube drainage in all cases . Mean operating time in group A and group B was 45 + /- 10 minutes and 73 + /- 6 minutes respectively ( p Postoperative wound dehiscence in group A and group B was observed in 2 and 11 cases respectively ( p Incisional hernia developed in 8 patients in group B and none in group A ( p adhesion-obstruction ( p wound sepsis , pelvic abscess and mortality were not significant . Mean hospital stay in groups A and B was 12.4 days and 16.8 days respectively ( p laparotomy via the Rutherford-Morrison incision may significantly reduce postoperative wound complications and morbidity without significantly altering the overall outcome", "OBJECTIVE To evaluate the fertility outcome after laparoscopic surgery for ectopic pregnancy . DESIGN A r and omized trial versus laparotomy was performed between May 1987 and June 1989 . SETTING The study was conducted in a clinical university center , the Sahlgrens Hospital . PATIENTS A group of 105 patients with tubal pregnancy were stratified with regard to risk determinants and age and r and omized to laparoscopy or laparotomy . Eighty-seven patients who desired pregnancy were evaluated for subsequent fertility outcome . INTERVENTIONS Linear salpingotomy was performed in both surgical groups . MAIN OUTCOME MEASURE We evaluated the fertility outcome after laparoscopic salpingotomy for comparison with the outcome after laparotomy . RESULTS There was no difference between the groups in the overall fertility outcome . A substantially higher proportion of patients in the laparotomy group were subjected to adhesiolysis performed at a second-look laparoscopy . CONCLUSIONS The fertility prospect s are not impaired by laparoscopic surgery . Adhesiolysis at a second-look laparoscopy , especially after laparotomy , might be beneficial in selected cases and may serve to improve subsequent fertility", "OBJECTIVE To compare the prognostic value of salpingoscopy with a current classification system of adnexal adhesions and distal tubal occlusion in patients with tubal infertility undergoing reconstructive tubal surgery . DESIGN Prospect i ve clinical study . SETTING Department of Obstetrics and Gynecology of the Catholic University , a tertiary care University Center in Rome , Italy . PATIENTS Fifty-five infertile patients with either adnexal adhesions ( 29 patients ) or hydrosalpinx ( 26 patients ) undergoing reconstructive tubal surgery . INTERVENTIONS Salpingoscopy performed concomitantly to salpingo-ovariolysis or salpingoneostomy at the time of either operative laparoscopy or laparotomy using microsurgical techniques . MAIN OUTCOME MEASURES Salpingoscopic findings were compared with a current classification system of adnexal adhesions and distal tubal occlusion . The patients were followed for a mean follow-up of 49 months ; the pregnancy rates achieved were correlated with the salpingoscopic findings and the classification system used . RESULTS There was a significant correlation between the salpingoscopic grade and the occurrence of a term pregnancy for both the salpingo-ovariolysis and salpingoneostomy groups of patients . There was no significant correlation between the classification system used and the occurrence of a term pregnancy for both groups of patients . CONCLUSION Salpingoscopy plays an important role in selecting the patients who may benefit the most from reconstructive tubal surgery", "BACKGROUND Adhesion-related readmissions are frequent sequelae to gynaecological surgery . Attempts to prevent adhesions by separating healing peritoneal surfaces include site-specific barriers and hydroflotation by instilled solutions . Rapid absorption limits the effectiveness of solutions such as Ringer 's lactated saline ( RLS ) . This pilot study assessed the safety , tolerability and preliminary effectiveness of a non-viscous , iso-osmolar solution of 4 % icodextrin , an alpha-1,4 glucose polymer with prolonged intraperitoneal residence , in reducing adhesions after laparoscopic gynaecological surgery . METHODS Women aged > or = 18 years , requiring laparoscopic adnexal surgery ( n = 62 ) , were entered into a r and omized , open-label , assessor-blinded , multicentre study to compare 4 % icodextrin with RLS . Treatments were coded in blocks of four with equal r and omization to each group , and pre-allocated to consecutively numbered patients . At least 100 ml per 30 min was used for intra-operative lavage , with 1 l instilled post-operatively . Per protocol analysis included all eligible patients ( n = 53 ) ; reformation analysis required one or more baseline adhesion ( n = 42 ) . Incidence , extent and severity of post-operative adhesions were assessed at second-look laparoscopy after 6 - 12 weeks . Procedures were video-taped for third party , blinded assessment . RESULTS Safety and tolerability ( laboratory variables , adverse events , clinical follow-up ) were good with no difference between treatments . A shift analysis of incidence-ranked adhesions ( n = 53 ) showed apparent improvements in more patients with icodextrin than RLS ( 37 versus 15 % ; not significant ) . Adhesion score reduction ( n = 42 ) was more frequent in icodextrin- than RLS-treated patients : incidence ( 52 versus 32 % ) , extent ( 52 versus 47 % ) , and severity ( 65 versus 37 % ) . Despite greater baseline adhesions , median reformation was less after icodextrin ( 24 % ) than RLS ( 60 % ) . The pilot study group sizes were not powered for statistical significance . CONCLUSIONS In this preliminary study , 4 % icodextrin lavage plus instillation was well tolerated and reduced adhesion formation and reformation following laparoscopic gynaecological surgery . A Phase III pivotal study is currently in progress", "Background Minimizing peritoneal tissue injury during abdominal surgery has the benefit of reducing postoperative inflammatory response , pain , and adhesion formation . Ultrasonic dissection seems to reduce tissue damage . This study aim ed to compare electrocautery and ultrasonic dissection in terms of peritoneal tissue ischemia measured by microdialysis . Methods In this study , 18 Wistar rats underwent a median laparotomy and had a peritoneal microdialysis catheter implanted in the left lateral sidewall . The animals were r and omly assigned to receive two st and ard peritoneal incisions parallel to the catheter by either ultrasonic dissection or electrocautery . After the operation , sample s of microdialysis dialysate were taken every 2 h until 72 h postoperatively for measurements of pyruvate , lactate , glucose , and glycerol , and ratios were calculated . Results The mean lactate – pyruvate ratio ( LPR ) , lactate – glucose ratio ( LGR ) , and glycerol concentration were significantly higher in the electrocautery group than in the ultrasonic dissection group until respectively 34 , 48 , and 48 h after surgery . The mean areas under the curve ( AUC ) of LPR , LGR , and glycerol concentration also were higher in the electrocautery group than in the ultrasonic dissection group ( 4,387 vs. 1,639 , P = 0.011 ; 59 vs. 21 , P = 0.008 ; 7,438 vs. 4,169 , P = 0.008 , respectively ) . Conclusion Electrosurgery causes more ischemic peritoneal tissue damage than ultrasonic dissection ", "The effects of pelvic and periaortic peritoneal closure or ( non-closure ) on morbidity and adhesion formation were prospect ively compared in 102 patients with ovarian cancer who had undergone a pelvic and periaortic lymphadenectomy . Hysterectomy with bilateral salpingoophorectomy , bilateral pelvic and periaortic lymphadenectomy , omentectomy , appendectomy and lysis of pelvic adhesions for the st and ardization of initial adhesion scores was performed on all patients . The pelvic and periaortic peritoneum were re-approximated in group I ( n = 50 ) patients , and left open in group II ( n = 52 ) patients . The groups were similar for mean age , previous surgery , tumour histology and disease stage . Morbidity characteristics such as blood loss , transfusion rate , post-operative infectious and non-infectious complications , and total hospital stay were also similar . After six courses of PAC ( cisplatin 50 mg/m(2 ) , Adriamycin 50 mg/m(2 ) , cyclophosphamide 500 Mg/M(2 ) ) chemotherapy , all patients underwent a second-look laparotomy . Persistent cancer was detected in 49 of 102 ( 48.03 % ) patients . Adhesion scores were detected at the time of second-look laparotomy . Adhesion scores for group I ( 8.9 + /- 2.9 ) were significantly higher than the group II ( peritoneum non-closure ) ( 5.8 + /- 2.3 ) ( P morbidity , but leaving the pelvic and periaortic peritoneum open significantly decreased the adhesion formation", "OBJECTIVE We sought to determine the effect of nonclosure of the visceral and parietal peritoneum during cesarean section on the formation of adhesions . STUDY DESIGN This was a prospect i ve r and omized trial of 533 women undergoing primary cesarean section ; in 256 the peritoneum was left open and in 277 it was closed . Fifty women in the nonclosure group and 47 women in the closure group were subsequently evaluated intraoperatively at a repeat cesarean . The presence of adhesions and their severity were evaluated at several sites . RESULTS The nonclosure and closure groups were comparable with regard to the proportion of patients with adhesions at any site ( 60 % vs 51 % , respectively ; P = .31 ) . Time from incision to delivery was comparable in the nonclosure and closure groups ( 8.98 ± 4.7 vs 9.32 ± 5.2 minutes , respectively ; P = .84 ) . CONCLUSION Closure or nonclosure of the peritoneum at cesarean section did not lead to large differences in the adhesion rate ", "BACKGROUND The study was carried out to clarify the incidence of post-operative tubal adhesions , patency rate and pregnancy outcome after laparoscopic salpingotomy with and without suturing for tubal pregnancy . METHODS From May 1996 to December 2002 , a total of 97 cases of tubal pregnancy were treated in our centre by laparoscopic conservative surgery . The successful salpingotomy cases were r and omly assigned to undergo salpingotomy without suturing ( group I ; n = 43 ) or with suturing ( group II ; n = 32 ) . We compared these patients and assessed their surgical and pregnancy outcome by second look laparoscopy ( SLL ) 3 months after the first operation . RESULTS Seventy-five cases ( 77 % ) were treated successfully by salpingotomy at initial laparoscopic surgery , and the remaining 22 cases were unsuccessful because of bleeding or complete tubal damage . Pelvic findings were assessed at SLL in 21 of 43 cases ( 49 % ) in group I and 17 of 32 ( 53 % ) in group II . There were no significant differences in gestational age , ectopic site , tubal diameter , tubal condition , intraperitoneal haemorrhage and pre-operative HCG levels between the two groups . Only the operation time was longer in group II than in group I ( 91 + /- 15 versus 69 + /- 15 min , P tubal patency rate of the treated side was 90 % ( 19/21 ) in group I and 94 % ( 16/17 ) in group II . Also the peritubal adhesions were observed in 33 % ( 7/21 ) in group I and 29 % ( 5/17 ) in group II , and were mostly comprised of filmy adhesions . A tubal fistula occurred in two cases in each group . Pregnancy rate was 79 % ( 15/19 ) in group I and 92 % ( 12/13 ) in group II , and this did not reveal any significant difference of cumulative pregnancy rate between the groups . CONCLUSION We recommend laparoscopic linear salpingotomy as a useful method in the management of cases with tubal pregnancy who desire future pregnancy . This preliminary study emphasizes that the procedure involving suturing has no additional benefit over the non-suturing technique during salpingotomy", "STUDY OBJECTIVE To compare the effects of microlaparoscopy and decreased CO2 exposure on peritoneal microcirculation and potential adhesion formation after ovarian surgery with those of conventional operative laparoscopy . DESIGN Prospect i ve , r and omized study ( Canadian Task Force classification I ) . SETTING Teaching hospital . PATIENTS Eighteen women with polycystic ovary disease . INTERVENTIONS Microlaparoscopic or laparoscopic ovarian coagulation of the ovaries . MEASUREMENTS AND MAIN RESULTS Approximately 10 to 12 coagulation points were applied to each ovary . Two to 3 weeks after the initial surgery second-look microlaparoscopy was performed to determine the extent of adhesions in both groups . The frequency of adhesion formation and changes in glutathione peroxidase ( GSH-Px ) , superoxide dismutase ( SOD ) , catalase ( CAT ) , and glutathione ( GSH ) levels were studied in homogenized peritoneal tissues obtained during surgery in each group . RESULTS Clinical profiles were similar between groups . Mean exposure , amount , and pressure of CO2 were significantly less in the microlaparoscopy group ( p adhesions than the microlaproscopy group ( 24 % vs 48 % , p GSH-Px , SOD , CAT , and GSH levels were significantly lower in the laparoscopy group ( 0 . 425 micromol , 1.2 ng , 37.55 micromol , and 0.9 nmol vs 0.755 micromol , 2.l ng , 625 micromol , and 2.6 nmol , respectively ) . CONCLUSION Reduced exposure to and amount of CO2 during microlaparoscopy may result in decreased adhesion formation compared with conventional laparoscopy . This effect may possibly be due to lack of or minimal adverse effects on peritoneal microcirculation and cell-protective systems , which are proposed mechanisms for adhesion formation and closely related to peritoneal injury . In addition , microlaparoscopy may be a cost-effective alternative to conventional laparoscopy . ( J Am Assoc Gynecol Laparosc 6(2):159 - 163 , 1999", "BACKGROUND Peritoneal fibrinolysis is important in peritoneal wound healing processes and adhesion formation . The peritoneal fibrinolytic response to laparoscopy is merely unknown . In the present study we investigate the effect of short-term laparoscopy on the peritoneal fibrinolytic response and the influence of intra-abdominal pressure , light intensity and choice of dissection device on this response . METHODS There were 50 patients scheduled for laparoscopic cholecystectomy r and omized in five groups operated with various pressures , light intensities , and dissection devices . Peritoneal biopsies were taken at the beginning and the end of the procedure . Tissue concentrations of tissue-type plasminogen activator ( tPA ) , urokinase-type plasminogen activator ( uPA ) , plasminogen activator inhibitor type 1 ( PAI-1 ) , and the tPA-activity were measured using ELISA techniques . RESULTS There were no differences in tPA antigen , tPA-activity , uPA antigen , or PAI-1 antigen concentrations in biopsies taken at the beginning compared to sample s taken at the end of the operation . Different intra-abdominal pressures , light intensities and the choice dissection device did not affect any of the measured parameters . CONCLUSION Short-term laparoscopy does not affect the peritoneal fibrinolytic activity . The used intra-abdominal pressure , light intensity and choice of dissection device do not affect peritoneal activity during short-term laparoscopy", "STUDY OBJECTIVE To evaluate the chance of adhesion formation after laparoscopic salpingo-ovariolysis and determine the efficacy of early second-look laparoscopy ( SLL ) . DESIGN Prospect i ve , r and omized study ( Canadian Task Force classification I ) . SETTING Shiraz University hospitals . SUBJECT Ninety women with mean duration of infertility of 7.2 years . INTERVENTIONS Operative laparoscopy , with early SLL with adhesiolysis in 46 ( group 1 ) and no SLL in 44 women ( group 2 ) . MEASUREMENTS AND MAIN RESULTS Adnexal adhesions were evaluated according to American Society for Reproductive Medicine adhesion classification . Separation of newly reformed adhesions was performed at the time of SLL . Patients were followed for a year after operation without other infertility treatment . At the time of operation in group 1 , adnexal adhesions were grade d as severe ( class D ) in 19 women , moderate ( class C ) in 31 , mild ( class B ) in 28 , and minimal ( class A ) in 14 . Respective figures in group 2 were 10 , 30 , 34 , and 14 . After salpingo-ovariolysis these figures were 12 , 10 , 20 , and 50 in group 1 and 6 , 14 , 17 , and 51 in group 2 . In group 1 in whom early second-look laparoscopy was performed , at the start of the operation these figures were 17 , 20 , 21 , and 34 , and after operation 12 , 8 , 20 , and 52 , respectively . There were 11 term pregnancies in group 1 and 15 in group 2 . No women with severe adhesions in either group conceived . In group 1 , chances of term pregnancy were 18.75 % for those with moderate adhesions , 35.71 % for women with mild adhesions , and 42.86 % in patients with minimal adhesions . Respective figures in group 2 were 26.67 % , 41.18 % , and 57.14 % . CONCLUSION The chance of moderate and severe adhesion reformation after laparoscopic salpingo-ovariolysis was 40.2 % . Although separation of these adhesions could be performed more easily at the time of early SLL , the chance of pregnancy did not increase compared with that in patients who did not undergo SLL", "OBJECTIVE To determine whether non-closure of visceral and parietal peritoneum at LSCS has advantages over peritoneal closure with regard to postoperative complication and adhesions . STUDY DESIGN Prospect i ve r and omized controlled trial . SETTING Paholpolpayuhasena Hospital , Kanchanaburi province , Thail and SUBJECTS AND METHOD Three hundred and sixty full-term pregnant women undergoing first cesarean section were divided into 3 groups ( N = 120 ) . Group A : non-closure of both visceral and parietal peritoneum . Group B. non-closure of only visceral peritoneum . Group C : closure of both visceral and parietal peritoneum . Postoperative complications were compared . Adhesions were evaluated in 65 patients returning for a second LSCS and compared for severity of adhesions . The three groups were compared using statistical analysis . RESULT There was no significant statistical difference between group A and C , group B and C for postoperative complications or number of adhesion formation . However , adhesions in the closure group were more severe . CONCLUSIONS Closure of visceral and parietal peritoneum has no benefit over non-closure of visceral peritoneum and non-closure of both visceral and parietal peritoneum at LSCS", "OBJECTIVE To determine the incidence , site , and grade of ovarian adhesion formation after laparoscopic ovarian drilling ( LOD ) and analyze the association between the number of punctures made and the incidence and grade of adhesions , and evaluate the lateral distribution of the adhesions . DESIGN Prospect i ve clinical study . SETTING University hospital endocrine and infertility center . PATIENT(S ) Ninety-six anovulatory infertile women with polycystic ovarian syndrome ( PCOS ) treated with LOD . INTERVENTION(S ) Women were r and omized into two study groups of 48 women each , one treated with 6 punctures on the left ovary and 12 on the right , and the other treated with 6 punctures on the right ovary and 12 on the left . A short-term second-look minilaparoscopy was performed to evaluate postsurgical adhesion formation . MAIN OUTCOME MEASURE(S ) [ 1 ] Evaluation of the incidence and grade ( thin , dense , cohesive ) of ovarian adhesions ; [ 2 ] comparative analysis of the incidence and grade of ovarian adhesions between ovaries treated with 6 and 12 punctures ; and [ 3 ] comparative analysis of the incidence and grade of ovarian adhesions between the two sides . RESULT ( S ) Adhesion formation was detected in 54 of the 90 women ( 60 % ) and in 83 of the 180 ovaries treated ( 46 % ) . Dense adhesions were more likely to develop on the left ovaries to a statistically significant extent , and independently of the number of ovarian punctures performed ( odds ratio [ OR ] = 4.34 , 95 % confidence interval [ CI ] = 1.72 - 10.94 ) . Logistic regression analysis showed that the incidence of ovarian adhesions was independent of both number of punctures ( OR = 1.05 , 95 % CI = 0.58 - 1.88 ) and side ( OR = 1.37 , 95 % CI = 0.76 - 2.46 ) . CONCLUSION ( S ) The incidence of ovarian adhesion formation after LOD was high , and their extent and severity was not influenced by the number of ovarian punctures ; however , the left ovary appeared more prone to develop severe adhesions than the contralateral one", "OBJECTIVE Our purpose was to compare postoperative adhesion formation and reproductive outcome after the same ovarian surgical procedure performed by laparoscopy or laparotomy by means of microsurgical techniques . STUDY DESIGN Twenty-eight New Zeal and White female rabbits were r and omly assigned to laparotomy or laparoscopy for the same st and ardized surgical procedure : both ovaries were grasped with atraumatic forceps and longitudinally incised on the antimesenteric side from the cortex to the hilum with a microelectrode delivering a tissue power density of 66,666 W/cm . The rabbits were then mated , and 2 weeks later a second-look laparotomy was performed by a blinded observer for the evaluation of postoperative adhesions , number of corpora lutea in each ovary , number of embryos in the ipsilateral uterine horn , and nidation index for each side . RESULTS At second look no statistically significant differences were found in postoperative adhesion formation , number of corpora lutea , number of embryos , and nidation index between the laparoscopy and the laparotomy groups . CONCLUSION Laparoscopy or laparotomy for ovarian conservative surgery do not appear significantly different in postoperative adhesion formation and reproductive outcome in the rabbit model", "A prospect i ve , r and omized study comparing the result of salpingo-ovariolysis using the carbon dioxide ( CO2 ) laser and the microdiathermy needle was conducted . The pregnancy rate after laser surgery was 53.3 % ( n = 30 ) and after electrosurgery was 51.5 % ( n = 33 ) at 2-year follow-up . Although the surgery-conception interval after laser surgery ( 9.9 + /- 2.0 months ) tended to be shorter than after electrosurgery ( 13.1 + /- 2.0 months ) , no statistical difference was reached . This report suggests that there is no difference between the pregnancy rate after salpingo-ovariolysis with the use of the CO2 laser or with the use of the microdiathermy needle . The surgery-conception interval , however , tends to be shorter after laser surgery . A larger series of patients is required to clarify the latter", "OBJECTIVE To assess the efficacy of autocrosslinked hyaluronic gel in postsurgical adhesion prevention after laparoscopic myomectomy . DESIGN Prospect i ve , r and omized , controlled study . SETTING University of Naples \" Federico II\".Thirty-six infertile women with symptomatic myomas were r and omly divided into two groups of 18 patients each . INTERVENTION(S ) Laparoscopic myomectomy with subserous sutures or interrupted figure 8 sutures , with ( group A ) or without ( group B ) application of autocrosslinked hyaluronic acid ( HA ) gel . MAIN OUTCOME MEASURE(S ) Rate of postsurgical adhesions at 60 - 90 days of follow-up . The rate of subjects who developed postoperative adhesions was significantly lower in group A in comparison with group B ( 27.8 % vs. 77.8 % ) . In both groups , the rate of adhesions was significantly higher in patients treated with interrupted figure 8 sutures than with subserous sutures . CONCLUSION ( S ) Autocrosslinked HA gel is a promising resorbable agent barrier for the reduction of postoperative adhesions after laparoscopic myomectomy . Moreover , the type of suture is a factor influencing the postsurgical adhesion formation", "Background Abdominal surgery , peritonitis , and pelvic inflammatory disease often give rise to intra-abdominal adhesions . They may lead to chronic pain , infertility , bowel obstruction , etc . Development in surgical strategies in the last decade has result ed in an increase in laparoscopic procedures and , as a consequence , a steep rise in reported bowel lesions . Accordingly , noninvasive diagnostic tools are desirable to identify adhesions before abdominal surgery . This study was design ed to vali date transabdominal ultrasonography ( TAU ) and magnetic resonance imaging ( cine MRI ) for detection of abdominal wall adhesions . Methods Sixty patients scheduled for laparoscopic surgery were prospect ively enrolled . They were divided into two groups of 30 each ; previous abdominal surgery/peritonitis and no history of abdominal surgery/peritonitis . Before elective surgery , TAU and cine MRI were performed . Visceral slide was measured in nine predefined abdominal segments and compared with intra-operative data on abdominal wall adhesions . Results were obtained in a double-blinded fashion . Results Patient characteristics were similar in both groups . Cine MRI showed a sensitivity , specificity , and accuracy of 21.5 % , 87.1 % , and 72.4 % . TAU showed a sensitivity , specificity , and accuracy of 24 % , 97.9 % , and 81.3 % . Comparison of TAU and cine MRI showed no significant difference in the detection of adhesions to the abdominal wall ; however , TAU was significantly superior in depicting adhesion-free areas . Conclusions This study represents the first comparative study of TAU and cine MRI as noninvasive methods in detecting adhesions to the abdominal wall . Both methods are specific in detecting adhesion-free areas , and may serve as a diagnostic tool for future planning of laparoscopic surgery , elucidation of adhesion-related symptoms , and as a tool in the follow-up after ventral hernia repair with implantation of intraperitoneal mesh", "Objective To evaluate the clinical outcome of patients who underwent vaginal hysterectomy with or without peritoneal closure . Methods This study was a r and omized trial . Using computer-generated numbers , all patients undergoing vaginal hysterectomy without oophorectomy were r and omized to either no peritoneal closure ( n = 57 ) or routine peritoneal closure ( n = 49 ) . Patients were followed-up for a minimum of 1 year for development of complications and postoperative dyspareunia . At 4–6 postoperative weeks , the distance between the ovaries and the vaginal cuff was measured by ultrasound . Results Postoperative complications were similar in both groups . The incidence of deep-thrust dyspareunia at 6 and 12 months was also similar . No statistical differences between the two groups were noted in the ovary to vaginal cuff distances either overall or when patients with dyspareunia were considered separately . Conclusion The data in this study do not support the use of reperitonealization on a routine basis . However , because of a lack of statistical power , larger studies will be required to confirm this theory", "Objectives : To establish the incidence and predictive factors of enterotomy made during adhesiolysis in abdominal wall repair and to assess the impact of enterotomies and long-lasting adhesiolysis on postoperative morbidity such as sepsis , wound infection , abdominal complications and pneumonia , and socioeconomic costs . Background : Adhesions frequently complicate surgical repair of abdominal wall hernia . Enterotomies made during adhesiolysis specifically have a large impact on morbidity of patients , especially surgical site infections . Little is known on the incidence and burden of enterotomies and long-lasting adhesiolysis in abdominal wall repair . Methods : Between June 2008 and June 2010 demographics , disease characteristics and perioperative data of all patients undergoing elective abdominal wall repair were included in a prospect i ve cohort study that was focused on adhesiolysis-related problems . A trained research er observed all surgeries and collected data on adhesion location , tenacity , adhesiolysis time , and inadvertent organ damage such as enterotomies . Primary outcome was the incidence of enterotomy , and predictive factors for enterotomy were assessed through univariate and multivariate analyses . In addition , we evaluated the impact of adhesiolysis and enterotomy on morbidity . Results : A cohort of 133 abdominal wall repairs was analyzed . Adhesiolysis was required in 124 ( 93.2 % ) , with a mean adhesiolysis time of 35.7 ± 29.8 minutes . Thirty-three enterotomies were made in 17 patients ( 12.8 % ) . Two patients had a delayed diagnosed bowel perforation . Adhesiolysis time , hernia size greater than 10 cm , and fistula were significant predictive factors in univariate analysis . In multivariate analysis , only adhesiolysis time was a significant and independent predictive factor for enterotomy ( P = 0.004 ) . Trends toward an increased risk were seen for patients with mesh in situ and hernia size greater than 10 cm . Patients with enterotomy had significantly more urgent reoperations ( P = 0.029 ) , and they more often required parenteral feeding ( P = 0.037 ) . Moreover , patients with extensive adhesiolysis ( adhesiolysis time , > 30 minutes ) more often suffered from wound infection ( 9/63 vs 2/70 ; P = 0.025 ) , abdominal complications ( 5/63 vs 0/70 ; P = 0.022 ) , and sepsis ( 4/63 vs 0/70 ; P = 0.048 ) . Conclusions : One in 8 patients undergoing abdominal wall repair suffer inadvertent enterotomy following adhesiolysis . Adhesiolysis time predicts enterotomy . Morbidity in patients with extensive adhesiolysis and adhesiolysis complicated by enterotomy is high , inducing longer hospital stay and increased health care utilization", "Objective To compare closure and nonclosure of the peritoneum at radical abdominal hysterectonmy and pelvic node dissection with respect to postoperative morbidity . Methods Women with uterine cancer who underwent radical abdominal hysterectomy and node dissection type II or III of Piver-Rutledge were assigned r and omly to have a st and ard closure of pelvic and parietal peritoneum and placement of a T-shaped suction drain or to have the peritoneum left open but the vagina closed and two abdominal drains placed . Adjuvant radiotherapy was given to patients with risk factors . The postoperative incidence of lymphocysts ( within 8 weeks from the operation and after 1 year ) and infection-related and non-infection-related complications were analyzed . Results One hundred twenty subjects were enrolled , of whom 59 had peritoneal closure and 61 did not . Both groups were similar with regard to age , weight , nodes removed , nodal metastases , operative time , type of surgery , need for transfusion , and incidence of postoperative radiotherapy . The median follow-up was 36 months ( range 11–72 ) . Eleven patients died , four because of treatment-related complication . The amount of drainage was significantly higher in the closed group than in the unclosed group ( median 740 mL , range 50–5980 versus median 340 mL , range 40–4000 ; P incidence of asymptomatic lymphocysts was similar in the closed and open groups at 2 weeks ( 17 of 59 versus 15 of 6 , respectively ) , at 8 weeks ( eight of 56 versus ten of 61 , respectively ) , and after 1 year ( one of 21 versus four of 22 , respectively ) . No difference was found between closed and open groups in terms of symptomatic lymphocysts ( one of 59 versus two of 61 , respectively ) , wound and pelvic infection ( seven of 59 versus 11 of 61 , respectively ) , febrile morbidity ( two of 59 versus one of 61 , respectively ) , and obstruction ( zero of 59 versus one of 61 , respectively ) . Conclusion Nonclosure of the peritoneum at radical abdominal hysterectomy and node dissection is not hazardous and is not associated with an increased incidence of infection- or adhesion-related complications", "OBJECTIVE To evaluate the efficacy of an oxidized regenerated cellulose adhesion barrier as an adjuvant in preventing postoperative adhesions in infertile women undergoing reconstructive surgery . STUDY DESIGN Thirty-eight cases of reconstructive surgery that could be followed up for more than two years ( myomectomy 19 , cystectomy 5 , tuboplasty 10 , uteroplasty 4 ) at the Fujita Health University Hospital were evaluated retrospectively . The barrier ( Intercede , Johnson & Johnson ) was used to cover the surgical site in 23 of these cases ( Intercede group ) ; no adjuvant was used in 15 cases , which represent the surgical control group ( Intercede - group ) , including 23 second-look operation cases ( 16 in the Intercede and 7 in the control group ) . Postoperative adhesion prevention and pregnancy rates were estimated . RESULTS At the second-look operation , six cases ( 37.5 % ) in the Intercede + group and six ( 85.7 % ) in the Intercede - group had postoperative adhesions . No significant difference was found in either intensity or area covered with adhesions between the two groups . Eighteen cases ( 78.3 % ) in the Intercede and seven ( 46.7 % ) in the Intercede - group conceived during the follow-up period . CONCLUSION The use of Intercede significantly reduced the rate of postoperative adhesion formation , with a statistically significant increase in the pregnancy rate as compared to the surgical controls", "Introduction Although Seprafilm ® has been demonstrated to reduce adhesion formation , it is not known whether its usage would translate into a reduction in adhesive small-bowel obstruction . Methods This was a prospect i ve , r and omized , multicenter , multinational , single-blind , controlled study . This report focuses on those patients who underwent intestinal resection ( n = 1,701 ) . Before closure of the abdomen , patients were r and omized to receive Seprafilm ® or no treatment . Seprafilm ® was applied to adhesiogenic tissues throughout the abdomen . The incidence and type of bowel obstruction was compared between the two groups . Time to first adhesive small-bowel obstruction was compared during the course of the study by using survival analysis methods . The mean follow-up time for the occurrence of adhesive small-bowel obstruction was 3.5 years . Results There was no difference between the treatment and control group in overall rate of bowel obstruction . The incidence of adhesive small-bowel obstruction requiring reoperation was significantly lower for Seprafilm ® patients compared with no-treatment patients : 1.8 vs. 3.4 percent ( P reduction in adhesive small-bowel obstruction requiring reoperation of 1.6 percent and a relative reduction of 47 percent . In addition , a stepwise multivariate analysis indicated that the use of Seprafilm ® was the only predictive factor for reducing adhesive small-bowel obstruction requiring reoperation . In both groups , 50 percent of first adhesive small-bowel obstruction episodes occurred within 6 months after the initial surgery with nearly 30 percent occurring within the first 30 days . Additionally no first adhesive small-bowel obstruction events were reported in Years 4 and 5 of follow-up . Conclusions The overall bowel obstruction rate was unchanged ; however , adhesive small-bowel obstruction requiring reoperation was significantly reduced by the use of Seprafilm ® , which was the only factor that predicted this outcome", "OBJECTIVE Women with ectopic pregnancy ( EP ) who have been operated on by laparoscopy are thought to have improved subsequent fertility , probably because of less adhesion formation . We aim ed to evaluate the adhesion formation after laparoscopy as compared with laparotomy in a r and omized trial . DESIGN One hundred five patients with tubal pregnancy were stratified with regard to age and risk factors and r and omized to surgery by laparoscopy or laparotomy . To evaluate adhesion formation and tubal status , 73 patients with strong desire of pregnancy underwent a second-look laparoscopy . The adhesion status at the ipsilateral and contralateral side at primary surgery was compared with the status at second-look laparoscopy . RESULTS Patients operated on by laparotomy developed significantly more adhesions at the operated side than patients operated on by laparoscopy ( P less than 0.001 ) . Substantially more patients in the laparotomy group underwent adhesiolysis at second-look laparoscopy than did patients in the laparoscopy group . Tubal patency did not differ between the groups . CONCLUSIONS Laparoscopic treatment of EP results in less impairment of the pelvic status compared with conventional conservative surgery", "Closure of vertical laparotomy wounds was r and omized between a two‐layer technique of continuous catgut to peritoneum and continuous nylon to sheath and a one‐layer technique in which the peritoneal suture line was omitted . In 162 two‐layer closures there were 4 burst abdomens and 7 wound hernias ( 6·8 per cent wound failures ) ; in 164 one‐layer closures there were 5 burst abdomens and 7 hernias ( 7·3 per cent failures ) . Of 21 patients in this series with jaundice , the abdominal wounds dehisced in 3 , and 4 patients developed incisional hernias ( 33·3 per cent failures ) compared with a 5·2 per cent failure rate in the 305 non‐jaundiced patients ( P < 0·01 )", "The effect of visceral peritoneal closure after conventional abdominal hysterectomies and Wertheim-Meigs radical operations was studied clinical ly . No considerable differences were found in the postoperative staying period ; however , the incidence of complications were less in the peritoneal non-closure group ( n = 91 ) than in the control , peritonealized group ( n = 149 ) . Significantly lower was the number of postoperative irregular pyelogram in cases without peritoneal closure ( n = 25 ) of radical abdominal operations than in the control group ( n = 49 ) with peritoneal suturing . We therefore suggest that the lack of suturing of visceral peritoneums has some advantages after abdominal hysterectomies and especially has benefits for Wertheim-Meigs operations", "Long‐term results of laparoscopically assisted versus open ileocolic resection for Crohn 's disease were evaluated in a r and omized trial", "PURPOSE : We have previously reported the five-year results of a r and omized trial comparing laparoscopic and open resection for cancer of the upper rectum and rectosigmoid junction . The aim of this follow-up study is to report on the long-term morbidity and ten-year oncologic outcomes among the subgroup of patients with upper rectal cancer . METHODS : From September 1993 to October 2002 , 153 patients with upper rectal cancer were r and omly assigned to receive either laparoscopic-assisted ( n = 76 ) or open ( n = 77 ) anterior resection . Patients were last followed up in December 2007 . Long-term morbidity , survival , and disease-free interval were prospect ively recorded . Data were analyzed by intention-to-treat principle . RESULTS : The demographic data of the two groups were comparable . More patients in the open group developed adhesion-related bowel obstruction requiring hospitalization ( P = 0.001 ) and intervention . The overall long-term morbidity rate was also significantly higher in the open group ( P = 0.012 ) . After curative resection , the probabilities of cancer-specific survival at ten years of the laparoscopic-assisted and open groups were 83.5 percent and 78.0 percent , respectively ( P = 0.595 ) , and their probabilities of being disease-free at ten years were 82.9 percent and 80.4 percent , respectively ( P = 0.698 ) . CONCLUSION : Laparoscopic-assisted anterior resection for upper rectal cancer is associated with fewer long-term complications and similar ten-year oncologic outcomes when compared with open surgery", "STUDY OBJECTIVE To determine the frequency of postoperative adhesions to the anterior abdominal wall peritoneum that could affect safe placement of the initial laparoscopic umbilical cannula at subsequent procedures . DESIGN Prospect i ve cohort study . SETTING Reproductive endocrinology and infertility service of a tertiary care referral hospital . PATIENTS Two hundred fifteen women , 124 with prior abdominal surgery and 91 with no prior surgery . INTERVENTIONS Surgical histories were review ed , abdominal skin scars noted , and extent of anterior abdominal wall adhesions prospect ively recorded . Statistical analysis was performed with the chi2 test . MEASUREMENTS AND MAIN RESULTS No anterior abdominal wall adhesions were present in 91 patients with no previous surgery or 45 patients with previous laparoscopy ( 12 had more than 1 laparoscopy ; p laparotomy ) . Seventeen ( 59 % ) of 29 patients with a midline vertical incision had anterior wall adhesions ( p suprapubic transverse incision had anterior wall adhesions ( p adhesions involved omentum and 29 % included bowel . CONCLUSION Prior laparotomy , whether through a midline vertical or suprapubic transverse incision , significantly increased the frequency of anterior abdominal wall adhesions , and these adhesions may complicate the placement of the laparoscopic cannula through the umbilicus", "OBJECTIVE To determine the frequency of peritoneal and visceral adhesions to the umbilical region according to past surgical history and to estimate the risk of bowel injury with blind insertion of the principal trocar-cannula . DESIGN Prospect i ve , unicentric study by a single operator . SETTING Clinique Saint-Sernin and Polyclinique de Bordeaux , Bordeaux , France . PATIENT(S ) Eight hundred fourteen patients undergoing diagnostic or operative laparoscopy were classified into four groups based on their history of abdominal surgery : group I ( n = 469 ) , no previous abdominal surgery ; group II ( n = 125 ) , prior laparoscopic surgery ; group III ( n = 131 ) , previous laparotomy with a horizontal supra-pubic incision ; group IV ( n = 89 ) , previous laparotomy with a midline incision . INTERVENTION(S ) Initial microlaparoscopy performed through the left upper quadrant of the abdomen , inspection of the anterior abdominal wall and particularly the umbilical area for the presence of adhesions . Patients who had adhesions were assessed as to whether or not they were at significant risk of injury from blind insertion of the principal trocar . MAIN OUTCOME MEASURE(S ) Incidence of umbilical adhesions and the potential risk of bowel injury with blind insertion of the umbilical ( principal ) trocar . RESULT ( S ) Umbilical adhesions were found in 9.82 % of the 814 cases . The rates of umbilical adhesions were as follows : group I , 0.68 % ; group II , 1.6 % ; group III , 19.8 % ; and group IV , 51.7 % . Severe adhesions with potential risk of bowel injury with blind insertion of the umbilical trocar in the four groups were 0.42 % , 0.80 % , 6.87 % , and 31.46 % , respectively . CONCLUSION ( S ) Women with previous laparotomy have a higher incidence of umbilical adhesions , especially in case of midline incision . Preliminary inspection of the umbilical area with a microlaparoscope and insertion of the umbilical trocar under direct vision are recommended for patients at risk for adhesions to reduce complications associated with insertion of the principal ( umbilical ) trocar", "OBJECTIVE To assess the safety and efficacy of Seprafilm ( HAL-F ) , Bioresorbable Membrane , ( Genzyme Corporation , Cambridge , MA ) in reducing the incidence , severity , extent , and area of uterine adhesions after myomectomy . DESIGN Prospect i ve , r and omized , blinded , multicenter study . Adhesion reduction was assessed by an independent , blinded , gynecologic surgeon who review ed videotapes of each patient 's second-look laparoscopy . SETTING Nineteen institutions across the United States . PATIENT(S ) One hundred twenty-seven women undergoing uterine myomectomy with at least one posterior uterine incision > or = 1 cm in length . INTERVENTION(S ) Patients were r and omized to treatment with Seprafilm or to no treatment at the completion of the myomectomy . MAIN OUTCOME MEASURE(S ) The incidence , severity , extent , and area of uterine adhesions at second-look laparoscopy . RESULT ( S ) The incidence , measured as the mean number of sites adherent to the uterine surface , was significantly less in treated patients ( 4.98 + /- 0.52 [ mean + /- SEM ] sites ) than in no treatment patients ( 7.88 + /- 0.48 sites ) as were the mean uterine adhesion severity scores ( 1.94 + /- 0.14 versus 2.43 + /- 0.10 ; treatment versus no treatment , respectively ) , mean extent scores ( 1.23 + /- 0.12 versus 1.68 + /- 0.10 ) , and mean area of adhesions ( 13.2 + /- 1.67 versus 18.7 + /- 1.66 cm2 ) . No adverse events occurred that were judged to be related to the use of Seprafilm . CONCLUSION ( S ) In this multicenter study , treatment of patients after myomectomy with Seprafilm significantly reduced the incidence , severity , extent , and area of postoperative uterine adhesions . Additionally , Seprafilm treatment was not associated with an increase in postoperative complications" ]	411890b4-06ff-11f0-808a-c43d1ab1c353
Attention-deficit hyperactivity disorder ( ADHD ) is a common childhood behavioural disorder . Systematic review s indicate that the community prevalence globally is between 2 % and 7 % , with an average of around 5 % . At least a further 5 % of children have substantial difficulties with overactivity , inattention , and impulsivity that are just under the threshold to meet full diagnostic criteria for ADHD . Estimates of the administrative prevalence ( clinical ly diagnosed or recorded ) vary worldwide , and have been increasing over time . However , ADHD is still relatively under-recognised and underdiagnosed in most countries , particularly in girls and older children . ADHD often persists into adulthood and is a risk factor for other mental health disorders and negative outcomes , including educational underachievement , difficulties with employment and relationships , and criminality . The timely recognition and treatment of children with ADHD-type difficulties provides an opportunity to improve long-term outcomes . This Review includes a systematic review of the community and administrative prevalence of ADHD in children and adolescents , an overview of barriers to accessing care , a description of associated costs , and a discussion of evidence -based pathways for the delivery of clinical care , including a focus on key issues for two specific age groups-younger children ( aged ≤6 years ) and adolescents requiring transition of care from child to adult services	[ "OBJECTIVE The purpose of this study was to estimate the prevalence and time trends in prescriptions of methylpheni date , dexamphetamine , and atomoxetine in children and adolescents , within three diagnostic groups : 1 ) autism spectrum disorder ( ASD ) , 2 ) attention-deficit/hyperactivity disorder ( ADHD ) , and 3 ) other psychiatric disorders . METHODS Data from six different national registers were used and merged to identify a cohort of all children and adolescents born in Denmark between 1990 and 2001 ( n=852,711 ) . Sociodemographic covariates on cohort members and their parents and lifetime prescriptions of methylpheni date , dexamphetamine , and atomoxetine were extracted from the registers . Prescriptions were also stratified by duration ( 9698 children and adolescents with ASD ( n=1577 ) , 61 % of 11,553 children and adolescents with ADHD ( n=7021 ) and 3 % of 48,468 children and adolescents with other psychiatric disorders ( n=1537 ) were treated with one or more ADHD medications . There was a significant increase in prescription rates of these medications for all three groups . From 2003 to 2010 , youth 6 - 13 years of age with ASD , ADHD , and other psychiatric disorders had 4.7-fold ( 4.4 - 4.9 ) , 6.3-fold ( 6.0 - 6.4 ) , and 5.5-fold ( 5.0 - 5.9 ) increases , respectively , in prescription rates of ADHD medications . CONCLUSION This is the largest study to date assessing stimulant treatment in children and adolescents with ASD , and is the first prospect i ve study quantifying the change over time in the prevalence of treatment with ADHD medications in a population -based national cohort of children and adolescents with ASD . The prevalence of stimulant treatment in youth with ASD of 16 % is consistent with earlier studies . The past decade has witnessed a clear and progressive increase in the prescription rates of medications typically used to treat ADHD in children and adolescents in Denmark . This increase is not limited to only those with ADHD , but includes others with neuropsychiatric disorders , including ASD . The risks and benefits of this practice await further study", "BACKGROUND This is the first r and omized controlled multicenter trial to evaluate the effect of two treatments of maternal attention-deficit hyperactivity disorder ( ADHD ) on response to parent-child training targeting children 's external psychopathology . METHODS Mother-child dyads ( n = 144 ; ADHD according to DSM-IV ; children : 73.5 % males , mean age 9.4 years ) from five specialized university outpatient units in Germany were central ly r and omized to multimodal maternal ADHD treatment [ group psychotherapy plus open methylpheni date medication ; treatment group ( TG ) : n = 77 ] or to clinical management [ supportive counseling without psychotherapy or psychopharmacotherapy ; control group ( CG ) : n = 67 ] . After 12 weeks , the maternal ADHD treatment was supplemented by individual parent-child training for all dyads . The primary outcome was a change in the children 's externalizing symptom scores ( investigator blinded to the treatment assignment ) from baseline to the end of the parent-child training 6 months later . Maintenance therapy continued for another 6 months . An intention-to-treat analysis was performed within a linear regression model , controlling for baseline and center after multiple imputations of missing values . RESULTS Exactly , 206 dyads were assessed for eligibility , 144 were r and omized , and 143 were analyzed ( TG : n = 77 ; CG : n = 66 ) . After 6 months , no significant between-group differences were found in change scores for children 's externalizing symptoms ( adjusted mean TG-mean CG=1.1 , 95 % confidence interval -0.5 - 2.7 ; p = .1854 ) , although maternal psychopathology improved more in the TG . Children 's externalizing symptom scores improved from a mean of 14.8 at baseline to 11.4 ( TG ) and 10.3 ( CG ) after 6 months and to 10.8 ( TG ) and 10.1 ( CG ) after 1 year . No severe harms related to study treatments were found , but adverse events were more frequent in TG mothers than in CG mothers . CONCLUSIONS The response in children 's externalizing psychopathology did not differ between maternal treatment groups . However , multimodal treatment was associated with more improvement in maternal ADHD . Child and maternal treatment gains were stable ( CCT-IS RCT N73911400 )", "OBJECTIVES To determine any long-term effects , 6 and 8 years after childhood enrollment , of the r and omly assigned 14-month treatments in the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder ( MTA ; N = 436 ) ; to test whether attention-deficit/hyperactivity disorder ( ADHD ) symptom trajectory through 3 years predicts outcome in subsequent years ; and to examine functioning level of the MTA adolescents relative to their non-ADHD peers ( local normative comparison group ; N = 261 ) . METHOD Mixed-effects regression models with planned contrasts at 6 and 8 years tested a wide range of symptom and impairment variables assessed by parent , teacher , and youth report . RESULTS In nearly every analysis , the originally r and omized treatment groups did not differ significantly on repeated measures or newly analyzed variables ( e.g. , grade s earned in school , arrests , psychiatric hospitalizations , other clinical ly relevant outcomes ) . Medication use decreased by 62 % after the 14-month controlled trial , but adjusting for this did not change the results . ADHD symptom trajectory in the first 3 years predicted 55 % of the outcomes . The MTA participants fared worse than the local normative comparison group on 91 % of the variables tested . CONCLUSIONS Type or intensity of 14 months of treatment for ADHD in childhood ( at age 7.0 - 9.9 years ) does not predict functioning 6 to 8 years later . Rather , early ADHD symptom trajectory regardless of treatment type is prognostic . This finding implies that children with behavioral and sociodemographic advantage , with the best response to any treatment , will have the best long-term prognosis . As a group , however , despite initial symptom improvement during treatment that is largely maintained after treatment , children with combined-type ADHD exhibit significant impairment in adolescence . Innovative treatment approaches targeting specific areas of adolescent impairment are needed", "BACKGROUND Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder ( ADHD ) , but no longer-term ( i.e. , > 4 months ) investigations have compared these 2 treatments or their combination . METHODS A group of 579 children with ADHD Combined Type , aged 7 to 9.9 years , were assigned to 14 months of medication management ( titration followed by monthly visits ) ; intensive behavioral treatment ( parent , school , and child components , with therapist involvement gradually reduced over time ) ; the two combined ; or st and ard community care ( treatments by community providers ) . Outcomes were assessed in multiple domains before and during treatment and at treatment end point ( with the combined treatment and medication management groups continuing medication at all assessment points ) . Data were analyzed through intent-to-treat r and om-effects regression procedures . RESULTS All 4 groups showed sizable reductions in symptoms over time , with significant differences among them in degrees of change . For most ADHD symptoms , children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care . Combined and medication management treatments did not differ significantly on any direct comparisons , but in several instances ( oppositional/aggressive symptoms , internalizing symptoms , teacher-rated social skills , parent-child relations , and reading achievement ) combined treatment proved superior to intensive behavioral treatment and /or community care while medication management did not . Study medication strategies were superior to community care treatments , despite the fact that two thirds of community-treated subjects received medication during the study period . CONCLUSIONS For ADHD symptoms , our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication . Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms , but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes", "Background Preschool hyperactivity is an early risk factor for adult mental health problems and criminality . Little is known about ; ( a ) the patterns of long‐term service costs associated with this behavioural marker in the general population and ( b ) the specific factors predicting hyperactivity‐related costs . We undertook a prospect i ve study investigating associations between preschool hyperactivity and average individual annual service costs up to late adolescent and young adulthood . Methods One‐hundred and seventy individuals rated as hyperactive by their parents and 88 nonhyperactive controls were identified from a community sample of 4,215 three years olds . Baseline information about behaviour/emotional problems and background characteristics were collected . At follow‐up ( when individuals were aged between 14 and 25 years ) information was obtained on service use , and associated costs since the age of three . Based on this information we calculated the average cost per annum incurred by each individual . Results Compared to controls , preschoolers with hyperactivity had 17.6 times higher average costs per annum across domains ( apart from nonmental health costs ) . These were £ 562 for each hyperactive individual compared with £ 30 for controls . Average annual costs decreased as a function of age , with higher costs incurred at younger ages . The effects of hyperactivity remained significant when other baseline factors were added to the model . Effects were fully mediated by later psychiatric morbidity . When the hyperactive group were examined separately , costs were consistently predicted by male gender and , for some cost codes , by conduct problems . Conclusions Preventative approaches targeting early hyperactivity may be of value . Services should be targeted towards high‐risk individuals with careful consideration given to the cost‐to‐benefit trade‐off of early intervention strategies", "OBJECTIVE To describe the long-term psychopharmacological treatment of children first diagnosed with attention-deficit/hyperactivity disorder ( ADHD ) as preschoolers . METHOD In a systematic , prospect i ve , naturalistic follow-up , 206 ( 68.0 % ) of the 303 children who participated in the Preschool ADHD Treatment Study ( PATS ) were reassessed 3 years ( mean age 7.4 years ) and 179 ( 59.1 % ) were reassessed 6 years ( mean age 10.4 years ) after completion of the controlled study . Pharmacotherapy and clinical data were obtained from the parents . Pharmacotherapy was defined as use of a specific class of medication for at least 50 % of the days in the previous 6 months . RESULTS At year 3 , a total of 34.0 % of the participants were on no pharmacotherapy , 41.3 % were on stimulant monotherapy , 9.2 % were on atomoxetine alone or with a stimulant , 8.3 % were on an antipsychotic usually together with a stimulant , and the remaining 7.2 % were on other pharmacotherapy ; overall , 65.0 % were on an indicated ADHD medication . At year 6 , a total of 26.8 % of the participants were on no pharmacotherapy , 40.2 % were on stimulant monotherapy , 4.5 % were on atomoxetine alone or with a stimulant , 13.4 % were on an antipsychotic , and 15.1 % were on other pharmacotherapy ; overall , 70.9 % were on an indicated ADHD medication . Antipsychotic treatment was associated with more comorbidity , in particular disruptive behavior disorders and pervasive development disorders , and a lower level of functioning . CONCLUSION In this study , the long-term pharmacotherapy of preschoolers with ADHD was heterogeneous . Although stimulant medication continued to be used by most children , about 1 child in 4 was off medication , and about 1 in 10 was on an antipsychotic", "CONTEXT Recent reports on the use of psychotropic medications for preschool-aged children with behavioral and emotional disorders warrant further examination of trends in the type and extent of drug therapy and sociodemographic correlates . OBJECTIVES To determine the prevalence of psychotropic medication use in preschool-aged youths and to show utilization trends across a 5-year span . DESIGN Ambulatory care prescription records from 2 state Medicaid programs and a salaried group-model health maintenance organization ( HMO ) were used to perform a population -based analysis of three 1-year cross-sectional data sets ( for the years 1991 , 1993 , and 1995 ) . SETTING AND PARTICIPANTS From 1991 to 1995 , the number of enrollees aged 2 through 4 years in a Midwestern state Medicaid ( MWM ) program ranged from 146,369 to 158,060 ; in a mid-Atlantic state Medicaid ( MAM ) program , from 34,842 to 54,237 ; and in an HMO setting in the Northwest , from 19,107 to 19,322 . MAIN OUTCOME MEASURES Total , age-specific , and gender-specific utilization prevalences per 1000 enrollees for 3 major psychotropic drug classes ( stimulants , antidepressants , and neuroleptics ) and 2 leading psychotherapeutic medications ( methylpheni date and clonidine ) ; rates of increased use of these drugs from 1991 to 1995 , compared across the 3 sites . RESULTS The 1995 rank order of total prevalence in preschoolers ( per 1000 ) in the MWM program was : stimulants ( 12.3 ) , 90 % of which represents methylpheni date ( 11.1 ) ; antidepressants ( 3.2 ) ; clonidine ( 2.3 ) ; and neuroleptics ( 0.9 ) . A similar rank order was observed for the MAM program , while the HMO had nearly 3 times more clonidine than antidepressant use ( 1.9 vs 0.7 ) . Sizable increases in prevalence were noted between 1991 and 1995 across the 3 sites for clonidine , stimulants , and antidepressants , while neuroleptic use increased only slightly . Methylpheni date prevalence in 2- through 4-year-olds increased at each site : MWM , 3-fold ; MAM , 1.7-fold ; and HMO , 3.1-fold . Decreases occurred in the relative proportions of previously dominant psychotherapeutic agents in the stimulant and antidepressant classes , while increases occurred for newer , less established agents . CONCLUSIONS In all 3 data sources , psychotropic medications prescribed for preschoolers increased dramatically between 1991 and 1995 . The predominance of medications with off-label ( unlabeled ) indications calls for prospect i ve community-based , multidimensional outcome studies", "OBJECTIVE To test the effectiveness of a telehealth service delivery model for the treatment of children with attention-deficit/hyperactivity disorder ( ADHD ) that provided pharmacological treatment and caregiver behavior training . METHOD The Children 's ADHD Telemental Health Treatment Study ( CATTS ) was a r and omized controlled trial with 223 children referred by 88 primary care providers ( PCPs ) in 7 communities . Children r and omized to the experimental telehealth service model received 6 sessions over 22 weeks of combined pharmacotherapy , delivered by child psychiatrists through videoconferencing , and caregiver behavior training , provided in person by community therapists who were supervised remotely . Children r and omized to the control service delivery model received treatment with their PCPs augmented with a telepsychiatry consultation . Outcomes were diagnostic criteria for ADHD and oppositional defiant disorder ( ODD ) and role performance on the V and erbilt ADHD Rating Scale ( VADRS ) completed by caregivers ( VADRS-Caregivers ) and teachers ( VADRS-Teachers ) and impairment on the Columbia Impairment Scale-Parent Version ( CIS-P ) . Measures were completed at 5 assessment s over 25 weeks . RESULTS Children in both service models improved . Children assigned to the telehealth service model improved significantly more than children in the augmented primary care arm for VADRS-Caregiver criteria for inattention ( χ(2)[4 ] = 19.47 , p ( χ(2)[4 ] = 11.91 , p = .02 ) , combined ADHD ( χ(2)[4 ] = 14.90 , p = .005 ) , ODD ( χ(2)[4 ] = 10.05 , p = .04 ) , and VADRS-Caregiver role performance ( χ(2 ) [ 4 ] = 12.40 , p = .01 ) and CIS-P impairment ( χ(2)[4 ] = 20.52 , p the telehealth service model had significantly more improvement in hyperactivity ( χ(2)[4 ] = 11.28 , p = .02 ) and combined ADHD ( χ(2)[4 ] = 9.72 , p = .045 ) . CONCLUSION The CATTS trial demonstrated the effectiveness of a telehealth service model to treat ADHD in communities with limited access to specialty mental health services . Clinical trial registration information-Children 's Attention Deficit Disorder With Hyperactivity ( ADHD ) Telemental Health Treatment Study ; http:// clinical trials.gov ; NCT00830700", "BACKGROUND The goal of this study is to assess changes in the prevalence of attention-deficit/hyperactivity disorder ( ADHD ) and methylpheni date prescriptions over the period 2000 to 2007 on the basis of data from a German statutory health insurance carrier . METHODS In a cross-sectional study , we analyzed data from a r and om sample of insurees of the AOK health insurance company in the German state of Hesse for the years 2000 to 2007 . Per calender year , 50,000 to 63,000 children and adolescents were retrospectively observed with respect to the documentation of ADHD diagnosis ( ICD-10 diagnosis F90 ) and the prescribing of methylpheni date ( ATC : N06BA04 ) . RESULTS In 2007 , the overall prevalence of ADHD in all age groups ( 0 - 18 years ) was 2.21 % ( 95 % CI : 2.09 - 2.34 ) . This figure was 45 % greater than the corresponding figure for the year 2000 . The prevalence increased by a larger amount among girls aged 6 to 18 years than among boys in the same age group ( + 69 % vs. + 53 % ) . In 2007 , 1.06 % ( 95 % CI : 0.98 - 1.16 ) of the children/adolescents received at least one prescription for methylpheni date ; this was a 96 % increase over the prescription rate for 2000 . A comparison of the two years 2000 and 2007 reveals a clear prevalence shift towards the older age groups , as well as an 82 % increase in the average number of daily doses per recipient . Outpatient departments of child and adolescent psychiatry initiated more treatments in 2007 than in 2000 . CONCLUSION The 1 % prevalence of methylpheni date use among children and adolescents that was found in this study is the same as that reported in other European countries , such as Switzerl and , the Netherl and s , and Norway . A drawback of our study is its limitation to a single insurance carrier in a single region . Nonetheless , data of this type are useful for monitoring . The findings suggest further issues worth study ing , e.g. , off-label use or the indications for treatment in older age groups", "OBJECTIVE To assess the impact of maternal attention-deficit/hyperactivity disorder ( ADHD ) symptoms on the effectiveness of a parent training ( PT ) program for preschool ADHD . METHOD Eighty-three 3-year-old children with ADHD and their mothers selected from two community cohorts living in Hampshire , Engl and ( 1992 - 93 and 1995 - 96 , respectively ) , completed an 8-week PT program . ADHD symptoms and a number of other parent and child factors , including adult ADHD symptoms , were measured prior to the start of treatment ( week 1 : T1 ) , immediately after treatment ( week 8 : T2 ) , and at 15 weeks follow-up ( week 23 : T3 ) . RESULTS Mothers were divided into three groups on the basis of their scores ( T1 ) on the Adult AD/HD Rating Scale ( high , medium , low ) . Children of mothers in the high-ADHD group displayed no improvement after PT , whereas the levels of ADHD symptoms of the children of mothers in either the medium or low ADHD groups reduced substantially ( F(4,60 ) = 3.13 , p .30 , p ADHD symptoms limit the improvement shown by children with ADHD after a program of PT . This effect was unrelated to other aspects of maternal mental health and child functioning . The treatment of parental ADHD may be a prerequisite for the success of psychosocial interventions for childhood ADHD", "OBJECTIVES To estimate the prevalence of attention deficit hyperactivity disorder ( ADHD ) pharmacological treatment , and its demographic and clinical details , and to estimate the proportion of patients in the target group who stopped ADHD treatment and investigate possible factors for continuation or cessation of treatment . DESIGN A pharmacoepidemiological study using an automated data base and a qualititative study using patient interviews . Part 1 was a pharmacoepidemiological study that provided accurate data on use and cessation of ADHD drugs . Part 2 was an in-depth interview study to investigate the reasons , processes and outcomes of treatment cessation . SETTING Part 1 : primary care using the General Practice Research Data base ( GPRD ) . Part 2 : secondary and tertiary care paediatric clinics , child and adolescent mental health and adult mental health clinics in London , Nottingham , Dundee and Liverpool . PARTICIPANTS Part 1 : patients were 15 - 21 years old during the study period ( 1 January 2001 and 31 December 2004 ) , had at least one prescription for methylpheni date , dexamfetamine or atomoxetine and had at least 1 year of research -st and ard data available in the GPRD . Part 2 : patients fulfilled Part 1 criteria , had a diagnosis of ADHD as detected by a predefined algorithm and had been treated with methylpheni date , dexamfetamine or atomoxetine for at least 1 year . Child and adolescent psychiatrists , adult psychiatrists and paediatricians involved in the treatment of young people with ADHD were also interviewed as part of the study . RESULTS Part 1 : prevalence of prescribing averaged across all ages increased eightfold , from 0.26 per 1000 patients in 1999 to 2.07 per 1000 patients in 2006 . The increase in prevalence in the younger patients was less evident in the older patients . Prevalence in 15-year-old males receiving a study drug prescription increased from 1.32 per 1000 patients in 1999 to 8.31 per 1000 patients in 2006 , whereas the prevalence in 21-year-olds rose from 0 per 1000 patients in 1999 to 0.43 per 1000 patients in 2006 . Survival analysis showed that the rate of treatment cessation largely exceeded the estimated rate of persistence of ADHD . The reduction in prescribing was most noticeable between 16 and 17 years of age . Kaplan-Meier analysis showed that approximately 18 % of patients restarted treatment if they had stopped treatment after the age of 15 . Patients who restarted treatment were more likely to restart within the first year following treatment cessation . Part 2 : the Child Health and Illness Profile ( CHIP ) was chosen as the quality of life question naire for the Part 2 study because the CHIP-CE scale has been vali date d in children with ADHD in the UK . Because of the age range of participants , the adolescent version ( CHIP-AE ) was administered to patients after interview . Of the 15 , a total of nine patients finished the question naire . Interviews showed that although some young people felt able to cope after stopping medication , others felt the need to restart to control symptoms . Some patients had difficulty re-engaging with services and clinicians recognised the lack of services for young adults . Patients continuing on treatment considered cessation as an option for the future , but were concerned about the process of stopping and its impact on behaviour . CONCLUSIONS Part 1 study demonstrated that the prevalence of prescribing by GPs to patients with ADHD dropped significantly from age 15 to 21 . The fall in prescribing was greater than the reported age-related decrease in symptoms , raising the possibility that treatment is prematurely discontinued in some young adults where ADHD symptoms persist . Part 2 of the study identified that some young adults had difficulty in obtaining treatment after discharge from paediatric services . Future work should include r and omised placebo-controlled trials into long-term treatment with stimulants , particularly methylpheni date" ]	411890f0-06ff-11f0-808a-c43d1ab1c353
INTRODUCTION Panic disorder ( PD ) is a prevalent psychiatric disorder characterized by unexpected and recurrent panic attacks . PD patients present significant psychosocial impairment and a high risk of psychiatric comorbidities and suicide . PD should be treated effectively as soon as the symptoms emerge because the longer these patients remain without treatment , the worse the prognosis will be . AREAS COVERED The authors carried out a systematic review of the literature regarding the pharmacological treatment of PD in the last 10 years . Only open studies , placebo-controlled studies or comparative clinical trials were selected . EXPERT OPINION Compounds with reported effectiveness in the treatment of PD included tricyclic antidepressants , benzodiazepines , serotonin selective reuptake inhibitors ( SSRIs ) , serotonin and noradrenaline reuptake inhibitors ( SNRIs ) and other drugs . SSRIs and SNRIs are the first-line compounds in the treatment of PD . These drugs were better tolerated than tricyclics and benzodiazepines as they had a low risk of dependence and overdosing complications . The serotonergic , noradrenergic and GABAergic pathways play a major role in the fear network and in the physiopathology of PD . A better underst and ing of the role of these neurotransmitter systems in PD will allow the development of more effective drugs for this psychiatric condition	[ "BACKGROUND Escitalopram , the therapeutically active isomer of the racemic selective serotonin reuptake inhibitor antidepressant citalopram , has shown significant anxiolytic effects in placebo-controlled clinical trials of social anxiety disorder , generalized anxiety disorder , and anxiety symptoms associated with major depression . This study evaluated the safety and efficacy of escitalopram in out patients diagnosed with panic disorder . METHOD Male and female out patients between 18 and 80 years of age meeting DSM-IV criteria for panic disorder , with or without agoraphobia , were r and omly assigned to 10 weeks of double-blind treatment with escitalopram , citalopram , or placebo in a study conducted from September 1999 to July 2001 . The primary measure of efficacy was panic attack frequency at week 10 relative to baseline , as assessed by the Modified Sheehan Panic and Anticipatory Anxiety Scale . RESULTS A total of 366 subjects ( 128 escitalopram patients , 119 citalopram patients , and 119 placebo patients ) received at least 1 dose of double-blind treatment . The frequency of panic attacks was statistically significantly improved ( p = .04 ) , and the increase in percentage of patients with zero panic attacks reached borderline significance ( p = .051 ) , in the escitalopram-treated group relative to the placebo-treated group . Both escitalopram and citalopram statistically significantly reduced panic disorder symptoms and severity versus placebo at endpoint ( p Panic and Agoraphobia Scale total score , the Clinical Global Impressions scale , the Patient Global Evaluation , and the Quality of Life Enjoyment and Satisfaction Question naire . Treatment with escitalopram was safe and well tolerated , with a similar incidence of the most common adverse events for the escitalopram and placebo groups . The rate of discontinuation for adverse events was 6.3 % for escitalopram , 8.4 % for citalopram , and 7.6 % for placebo . CONCLUSION Escitalopram is efficacious , safe , and well tolerated in the treatment of panic disorder", "RATIONALE Few r and omized , placebo-controlled trials have evaluated the comparative efficacy and tolerability of more than one pharmacological agent for panic disorder . OBJECTIVES The primary objective of this study was to compare the efficacy and tolerability of venlafaxine extended release ( ER ) with placebo in treating panic disorder . Secondary objectives included comparing paroxetine with venlafaxine ER and placebo . METHODS Out patients aged > or = 18 years ( placebo , n = 157 ; venlafaxine ER 75 mg , n = 156 ; venlafaxine ER 225 mg , n = 160 ; paroxetine , n = 151 ) , with a primary diagnosis of panic disorder ( + /-agoraphobia ) based on the Diagnostic and Statistical Manual of Mental Disorders ( Fourth Edition ) criteria for > or =3 months were r and omly assigned to receive venlafaxine ER ( titrated to 75 mg/day or 225 mg/day ) , paroxetine ( titrated to 40 mg/day ) , or placebo for 12 weeks . The primary efficacy measure was the percentage of patients free of full-symptom panic attacks ( > or = four symptoms ) at endpoint . Key secondary outcomes included the Panic Disorder Severity Scale ( PDSS ) mean score change and response . RESULTS At endpoint , all active treatment groups showed a significantly ( P free of full-symptom panic attacks , compared with placebo , and were superior ( P venlafaxine ER 225 mg group had significantly ( P mean PDSS score improvement than the paroxetine group ( -12.58 vs -11.87 ) and a significantly higher proportion of patients free of full symptom panic attacks ( 70.0 vs 58.3 % ) . Both drugs were generally well tolerated . CONCLUSION Venlafaxine ER 75 mg/days and 225 mg/days and paroxetine 40 mg/day were both well tolerated and effective for short-term treatment of panic disorder", "Panic disorder with or without agoraphobia is a common , often chronic and refractory anxiety disorder . Although a number of pharmacotherapies are now indicated for panic disorder , many patients do not respond to available interventions . We hypothesized that duloxetine , a serotonin‐norepinephrine reuptake inhibitor ( SNRI ) that has greater initial noradrenergic effects than venlafaxine , would have broad efficacy for individuals with panic disorder . Fifteen individuals with panic disorder with or without agoraphobia received 8 weeks of open label duloxetine flexibly dosed from 60 to 120 mg per day . Duloxetine treatment result ed in significant anxiolysis as measured by the primary outcome measure , the Panic Disorder Severity Scale ( PDSS ) ( paired t(df ) = 4.02(14 ) , P= 0.0013 ) , as well as measures of generalized anxiety , depression and quality of life ( all P < 0.05 ) . Although definitive conclusions are limited due to its small open‐label nature , this first prospect i ve study provides preliminary support for the efficacy of duloxetine for panic disorder and suggests larger r and omized controlled study is warranted", "Objective : To investigate the long‐term efficacy , prevention of relapse and safety of sertraline in the treatment of panic disorder", "A r and omized , double-blind , placebo-controlled , parallel-group study was conducted to evaluate the efficacy and safety of gabapentin in relieving the symptoms of panic disorder . One hundred three patients were r and omly assigned to receive double-blind treatment with either gabapentin ( dosed flexibly between 600 and 3,600 mg/day ) or placebo for 8 weeks . No overall drug/placebo difference was observed in scores on the Panic and Agoraphobia Scale ( PAS ) ( p = 0.606 ) . A post hoc analysis was used to evaluate the more severely ill patients as defined by the primary outcome measure ( PAS score > or = 20 ) . In this population , the gabapentin-treated patients showed significant improvement in the PAS change score ( p = 0.04 ) . In patients with a PAS score of 20 or greater , women showed a greater response than men regardless of treatment . Adverse events were consistent with the known side effect profile of gabapentin and included somnolence , headache , and dizziness . One patient experienced a serious adverse event during the study . No deaths were reported . The results of this study suggest that gabapentin may have anxiolytic effects in more severely ill patients with panic disorder", "INTRODUCTION Serotonergic agents have greater effectiveness than noradrenergic ones in the treatment of Panic Disorder ( PD ) . However preliminary studies suggested that reboxetine might be effective in the treatment of PD . We compared the effectiveness and tolerability of reboxetine and paroxetine in the treatment of PD . METHODS Sixty-eight patients with PD were assigned to treatment groups in a single-blind , r and omized design . Each patient was assessed at day 0 and 90 by the Panic Associated Symptoms Scale ( PASS ) , the Sheehan Disability Scale ( SDS ) and the Fear Question naire ( FQ ) . Side effects were also recorded . RESULTS Reduction of PASS scores was significantly greater in the paroxetine group than in the reboxetine one . Vice versa we did not find any significant differences for other outcome measures . Sexual dysfunction and weight gain were significantly less frequent in the reboxetine group . CONCLUSIONS The results showed a greater effect of paroxetine on panic attacks than reboxetine , while no differences for anticipatory anxiety and avoidance were found , suggesting a different role of noradrenaline and serotonin in the treatment of PD", "Mirtazapine is an antidepressant whose side effect profile differs from that of first-line agents ( selective serotonin reuptake inhibitors ) used in the treatment of panic disorder . The present study compared the effect of mirtazapine and fluoxetine in the treatment of panic disorder in a double-blind , r and omized , flexible-dose trial conducted with out patients . After a 1-week single-blind placebo run-in , 27 patients entered an 8-week double-blind phase in which they were r and omly assigned to treatment with either mirtazapine or fluoxetine . Both groups improved significantly in all but one efficacy measure ( P ANOVA showed no significant differences between the two treatment groups in number of panic attacks , Hamilton Anxiety Scale or Sheehan Phobic Scale , whereas measures of patient global evaluation of phobic anxiety were significantly different between groups ( F1,20 = 6.91 , P = 0.016 ) favoring mirtazapine . For the 22 patients who completed the study , the mean daily dose of mirtazapine was 18.3 + /- 1.3 vs 14.0 + /- 1.0 mg for fluoxetine at the endpoint . Weight gain occurred more frequently in the mirtazapine group ( 50 vs 7.7 % , P = 0.04 ) and nausea and paresthesia occurred more often in the fluoxetine group ( P = 0.01 ) . Results suggest that mirtazapine has properties that make it attractive for the treatment of panic disorder", "OBJECTIVE To assess the effectiveness of clonazepam , in a fixed dose ( 2 mg/day ) , compared with placebo in the treatment of panic disorder patients . METHOD 24 panic disorder patients with agoraphobia were r and omly selected . The diagnosis was obtained using the structured clinical interview for DSM-IV . All twenty-four subjects were r and omly assigned to either treatment with clonazepam ( 2 mg/day ) or placebo , during 6 weeks . Efficacy assessment s included : change from baseline in the number of panic attacks ; CGI scores for panic disorder ; Hamilton rating scale for anxiety ; and panic associated symptoms scale . RESULTS At the therapeutic endpoint , only one of 9 placebo patients ( 11.1 % ) were free of panic attacks , compared with 8 of 13 ( 61.5 % ) clonazepam patients ( Fisher exact test ; p=0,031 ) . CONCLUSION the results provide evidence for the efficacy of clonazepam in panic disorder patients", "BACKGROUND AND OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) are currently the first-line treatment for panic disorder , although up to 30 % of patients either do not respond to SSRIs or withdraw due to adverse events . Reboxetine , a selective norepinephrine reuptake inhibitor ( selective NRI ) , is effective in treating depression and may alleviate depression-related anxiety . This study aim ed to investigate the efficacy of reboxetine in the treatment of patients with panic disorder who did not respond to SSRIs . METHOD In this 6-week , open-label study , 29 adult out patients with panic disorder who had previously failed to respond to SSRI treatment received reboxetine 2 mg/day , titrated to a maximum of 8 mg/day over the first 10 days . Efficacy was assessed using the Panic Self- Question naire ( PSQ ) , the Hamilton Rating Scale for Anxiety ( HAM-A ) , the 17-item Hamilton Rating Scale for Depression ( HRSD ) and the Global Assessment of Functioning ( GAF ) Scale . RESULTS The 24 patients who completed the study responded well to reboxetine treatment . Significant improvement ( p number of daily panic attacks , and on the scales measuring anxiety , depression and functioning . Reboxetine was generally well tolerated . Five patients withdrew due to adverse events . CONCLUSIONS Reboxetine appears to be effective in the treatment of SSRI-refractory panic disorder patients and warrants further clinical investigation", "The purpose of our study was to evaluate the efficacy and tolerability of low-dose olanzapine augmentation in selective serotonin reuptake inhibitor (SSRI)-resistant panic disorder ( PD ) with or without agoraphobia . In this 12-week , open-label study , 31 adult out patients with treatment-resistant PD who had previously failed to respond to SSRI treatment were treated with fixed dose of olanzapine ( 5 mg/d ) in addition to SSRI . Efficacy was assessed using the Panic Attack and Anticipatory Anxiety Scale ( PAAAS ) , the Agoraphobic Cognitions Question naire ( ACQ ) , the Hamilton Rating Scale for Anxiety ( HAM-A ) , the Hamilton Rating Scale for Depression ( HAM-D ) , the Global Assessment of Functioning Scale ( GAF ) , and the Clinical Global Impression of Improvement ( CGI-I ) . Twenty-six patients completed the trial period with a dropout rate of 16.1 % . At week 12 , 21 patients were responders ( 81.8 % ) , and an overall improvement on all rating scales was observed in all patients both with or without agoraphobia . Fifteen patients ( 57.7 % ) achieved remission . Olanzapine was well tolerated and the most frequent adverse effects were mild-to-moderate weight gain and drowsiness . No extrapyramidal symptoms were reported . Olanzapine appears to be effective as augmentation strategy in the treatment of SSRI-resistant PD , but study limitations must be considered and placebo-controlled studies are needed", "OBJECTIVE To assess the efficacy and tolerability of controlled-release paroxetine ( paroxetine CR ) in the treatment of adults with panic disorder . METHOD Paroxetine CR ( 25 - 75 mg/day ; N = 444 ) was compared with placebo ( N = 445 ) in patients with DSM-IV panic disorder with or without agoraphobia in 3 identical , double-blind , placebo-controlled , 10-week clinical trials that were pooled for analysis . RESULTS Paroxetine CR was statistically superior to placebo in the primary outcome measure , percentage of patients who were free of panic attacks in the 2 weeks prior to endpoint . Of the total population that completed or prematurely terminated treatment , 63 % and 53 % of paroxetine CR- and placebo-treated patients , respectively , were panic-free during the final 2 weeks ( p paroxetine CR- and placebo-treated patients , respectively , were panic-free at week 10 ( p Paroxetine CR was also statistically superior to placebo on the global improvement and severity items of the Clinical Global Impressions scale and in reducing anxiety symptoms as measured by the Hamilton Rating Scale for Anxiety total score and total fear and avoidance on the Marks-Sheehan Phobia Scale . Adverse events leading to study withdrawal were minimal and occurred in 11 % of the paroxetine CR group and 6 % of the placebo group . Most of the treatment-emergent adverse events were rated as mild to moderate in severity and occurred early in the study . There were no unexpected adverse events , and serious adverse events were uncommon ( 10 [ 2.3 % ] of the 444 patients treated with paroxetine CR vs. 8 [ 1.8 % ] of the 445 patients treated with placebo ) . CONCLUSION Paroxetine CR is an effective and well-tolerated treatment for panic disorder . Paroxetine CR is associated with low rates of treatment-emergent anxiety as well as low dropout rates from adverse events", "Despite the acknowledged favorable side effects profile of selective serotonin reuptake inhibitors ( SSRIs ) , comparative studies have not found significant differences in efficacy between tricyclics ( TCAs ) such as imipramine and clomipramine , and SSRIs in the treatment of panic disorder . The present study focuses on treatment completers to inform patients who adhere to a recommended course of treatment on the possible differential patterns of improvement and of change in side effects between sertraline and imipramine . From an intent to treat consecutive sample of patients participating in the 24-week open phase protocol ized treatment of a long-term controlled maintenance/discontinuation study , 20 imipramine completers and 16 sertraline completers with moderate to severe baseline symptomatology were compared using primarily repeated measures analysis of variance on measures of symptom severity , on 15 side effects systematic ally elicited using an inventory and on heart rate and weight . The results revealed greater early improvement with imipramine compared to sertraline but no enduring differences beyond week 8 of treatments . Side effects , in particular dry mouth , constipation , tremors , sweating , and cardiovascular complaints increased more in severity and were more frequent and persistent during imipramine than sertraline but , except for the 10 beats/min increase in heart rate , side effects were clinical ly insignificant at the end of both treatments . Change in sexual complaints and weight did not differ between the treatments . The more favorable side effect profile of SSRIs versus TCAs was demonstrated even in the best case scenario of treatment completers . The more rapid improvement with imipramine needs replication but , tentatively , it may be attributed to the greater motivational effects toward action observed with noradrenergic or dual action antidepressants compared to SSRIs", "Panic disorder ( PD ) is an acute psychobiologic reaction manifested by intense anxiety and panic attacks , that occur unpredictably with subjective sense of intense apprehension or terror , accompanied by temporary loss of the ability to plan , think , or reason and the intense desire to escape or flee the situation . Panic attacks may last from a few seconds to an hour or longer . Symptoms typically include , among others , palpitations , tachycardia , hypertension , chest pain , dyspnoea , and fear of loosing control or going crazy and vague feeling of imminent doom or death . Since pharmacotherapy of PD includes the administration of selective serotonin reuptake inhibitors and tricyclic antidepressants , the objective of this study was to perform a pilot double blind clinical trial design ed to compare the effects of two studied drugs in the treatment of PD . A total number of 40 patients with a history of panic disorder were r and omly assigned into two groups of 20 patients each . Hamilton anxiety rating scale and St and ard Psychiatric Interview were methods for PD assessment . One group was treated with clomipramine hydrochloride ( ANAFRANIL ) 75 mg/day and the other with fluoxetine ( OXETIN ) 60 mg/day . Both drugs were administrated by mouth ( PO ) two times-a-day in equally divided doses for 6 weeks . Both studied agents produced similar antipanic effectiveness . Favourable response was achieved in 95 % of patients treated with fluoxetine and 90 % of patients treated with clomipramine . The onset of antipanic effects was quicker in all clomipramine treated patients , while fluoxetine produced more-favourable response in male patients . The duration of treatment with both antidepressants studied should be at least 10 weeks , instead of 6 weeks", "The demographic , clinical and therapeutic features of the respiratory subtype of panic disorder ( PD ) versus the non-respiratory subtype were studied in a prospect i ve design . Sixty-seven PD out patients ( DSM-IV ) , who had previously been categorized into respiratory ( n=35 ) and non-respiratory ( n=32 ) subgroups , were openly treated with clonazepam for a 3-year period . The principal measure of efficacy was the number of panic attacks , obtained from the Sheehan Panic and Anticipatory Anxiety Scale . In the first 8 weeks of treatment ( acute phase ) , the respiratory subtype group had a significantly faster response to clonazepam . During the follow-up ( weeks 12 - 156 ) , the two subgroups did not differ significantly in the number of panic attacks experienced from baseline to end point . Patients in the respiratory subtype were characterized by a later onset of disorder and a family history of PD . Patients in the non-respiratory subgroup had a significantly higher number of past depressive episodes than those in the respiratory subgroup . The respiratory subgroup had a faster response after 8 weeks of treatment and an equivalent response in the 3-year follow-up period . Clonazepam had a sustained therapeutic effect over the entire treatment period", "OBJECTIVE To evaluate the efficacy and tolerability of sertraline and imipramine in patients with comorbid panic disorder and major depressive disorder . METHOD Out patients meeting a DSM-IV diagnosis of panic disorder and concurrent major depressive disorder were r and omized in a 2:1 ratio to 26 weeks of double-blind treatment with either sertraline , in daily doses of 50 to 100 mg , or imipramine , in daily doses of 100 to 200 mg . Primary outcome measures were panic attack frequency ( derived from patient diaries ) and the Montgomery-Asberg Depression Rating Scale ( MADRS ) . RESULTS 138 patients were treated with sertraline ( 76 % female ; mean age = 40 years ) and 69 with imipramine ( 70 % female ; mean age = 40 years ) . The symptoms of both major depressive disorder and panic disorder responded significantly and equivalently to both drugs . Endpoint improvement with sertraline versus imipramine , respectively , on the MADRS was 11.1 + /- 10.8 versus 11.2 + /- 10.4 , and on the Clinical Global Impressions-Improvement scale ( CGI-I ) was 2.1 + /- 1.3 versus 2.4 + /- 1.6 . Among study completers , CGI-I responder rates were 88 % with sertraline and 91 % with imipramine . Treatment outcome was concordant for both diagnoses in approximately 70 % of patients and discordant in approximately 30 % . Overall , sertraline was significantly better tolerated with significantly fewer discontinuations due to adverse events ( 11 % vs. 22 % ; chi(2 ) = 4.39 , df = 1 , p = .04 ) . CONCLUSION Both sertraline and imipramine were found to be highly effective treatments for both major depressive disorder and panic disorder , with sertraline showing significantly greater tolerability and compliance during long-term treatment than imipramine", "Despite the widespread application of combined selective serotonin reuptake inhibitors ( SSRI ) and benzodiazepine treatment for panic disorder , there has been relatively little systematic assessment of the safety and efficacy of this therapeutic strategy . Although the limited number of studies to date suggest a more rapid onset of benefit with combined treatment , this study is the first to address the critical question of whether continued combined treatment confers superior efficacy . This study is a r and omized , double-blind , three-arm study in patients with panic disorder ( n = 60 ) , comparing the efficacy and safety of paroxetine and placebo ( PP ) , paroxetine coadministered with clonazepam followed by a tapered benzodiazepine discontinuation phase ( PC-D ) , and ongoing combination treatment ( PC-M ) . All treatment groups demonstrated significant improvement by endpoint . There was a significant advantage for the combined treatment groups early in treatment but , subsequently , outcome in all three groups was similar . A trend towards greater achievement of endpoint remission status for the PC-D group was attenuated when variability in baseline severity was considered . The results of this study should be interpreted in the context of a relatively moderate sample size and higher rates of early dropout . Combined treatment with paroxetine and clonazepam result ed in more rapid response than with the SSRI alone , but there was no differential benefit beyond the initial few weeks of therapy . Initiating combined treatment followed by benzodiazepine taper after a few weeks may provide early benefit while avoiding the potential adverse consequences of long-term combination therapy", "Only 70 % of patients respond to current treatments for panic disorder , and many discontinue drugs because of side effects . myo-Inositol , a natural isomer of glucose and a precursor for the second-messenger phosphatidyl-inositol system , has previously been found superior to placebo in the treatment of depression , panic disorder , and obsessive-compulsive disorder ( OCD ) , but a direct comparison with an established drug has never been performed . A double-blind , controlled , r and om-order crossover study was undertaken to compare the effect of inositol with that of fluvoxamine in panic disorder . Twenty patients completed 1 month of inositol up to 18 g/day and 1 month of fluvoxamine up to 150 mg/day . Improvements on Hamilton Rating Scale for Anxiety scores , agoraphobia scores , and Clinical Global Impressions Scale scores were similar for both treatments . In the first month , inositol reduced the number of panic attacks per week ( mean and SD ) by 4.0 ( 2 ) compared with a reduction of 2.4 ( 2 ) with fluvoxamine ( p = 0.049 ) . Nausea and tiredness were more common with fluvoxamine ( p = 0.02 and p = 0.01 , respectively ) . Because inositol is a natural compound with few known side effects , it is attractive to patients who are ambivalent about taking psychiatric medication . Continuing reports of inositol ’s efficacy in the treatment of depression , panic disorder , and OCD should stimulate replication studies", "The objective of this study was to determine the efficacy of pindolol as an augmentor of fluoxetine in treatment-resistant panic disorder ( PD ) . Twenty-five out patients having PD with or without agoraphobia were included . These patients had not responded to two different trials with antidepressants and an 8-week trial of fluoxetine 20 mg/day . Treatment-resistant PD was defined as a less than 20 % reduction in score on the Panic Self- Question naire ( number of attacks per week ) ( PSQ ) and the Clinical Anxiety Scale With Panic Attacks ( CAS+PA ) . These patients continued to receive fluoxetine 20 mg/day and were r and omly assigned to additionally receive either pindolol ( 2.5 mg three times daily ) or placebo for the following 4 weeks . Evaluations were performed weekly using the Hamilton Rating Scale for Anxiety , the Hamilton Rating Scale for Depression ( HAM-D ) , the CAS+PA , the NIMH Anxiety Scale , the PSQ , and the Clinical Global Impression Scale . The data were analyzed using a repeated- measures analysis of variance ( ANOVA ) and a t-test for independent sample s. Patients treated with the combination of pindolol and fluoxetine ( N = 13 ) demonstrated a significant improvement over the patients treated with fluoxetine and placebo on all rating scales , with the exception of HAM-D. The statistical differences were shown using the repeated- measures ANOVA ( baseline , week 2 , week 4 ) and also with t-tests from the second week of the trial . These preliminary results demonstrate that pindolol has an augmenting effect on fluoxetine in patients with treatment-resistant PD", "To date , no large-scale , controlled trial comparing a serotonin-norepinephrine reuptake inhibitor and selective serotonin reuptake inhibitor with placebo for the treatment of panic disorder has been reported . This double-blind study compares the efficacy of venlafaxine extended-release ( ER ) and paroxetine with placebo . A total of 664 nondepressed adult out patients who met DSM-IV criteria for panic disorder ( with or without agoraphobia ) were r and omly assigned to 12 weeks of treatment with placebo or fixed-dose venlafaxine ER ( 75 mg/day or 150 mg/day ) , or paroxetine 40 mg/day . The primary measure was the percentage of patients free from full-symptom panic attacks , assessed with the Panic and Anticipatory Anxiety Scale ( PAAS ) . Secondary measures included the Panic Disorder Severity Scale , Clinical Global Impressions -- Severity ( CGI-S ) and --Improvement ( CGI-I ) scales ; response ( CGI-I rating of very much improved or much improved ) , remission ( CGI-S rating of not at all ill or borderline ill and no PAAS full-symptom panic attacks ) ; and measures of depression , anxiety , phobic fear and avoidance , anticipatory anxiety , functioning , and quality of life . Intent-to-treat , last observation carried forward analysis showed that mean improvement on most measures was greater with venlafaxine ER or paroxetine than with placebo . No significant differences were observed between active treatment groups . Panic-free rates at end point with active treatment ranged from 54 % to 61 % , compared with 35 % for placebo . Approximately 75 % of patients given active treatment were responders , and nearly 45 % achieved remission . The placebo response rate was slightly above 55 % , with remission near 25 % . Adverse events were mild or moderate and similar between active treatment groups . Venlafaxine ER and paroxetine were effective and well tolerated in the treatment of panic disorder", "In this open label pilot study , we studied the efficacy of mirtazapine ( Remeron ) in panic disorder . Twenty-eight patients with a DSM-IV diagnosis of panic disorder , with or without agoraphobia ( 10 males/18 females ) , were included and 19 patients completed the study . The 15-week trial started with a 3-week single-blind placebo run-in period . After this run-in period , the 12-week active treatment phase started . As primary efficacy measures , we studied the decrease in the number of full symptom panic attacks and the number of patients completely free of panic during the last 3 weeks of the study . Seventy-four percent of the patients were considered responders , according to a decrease of at least 50 % in panic attack frequency . All primary and secondary efficacy measures showed a significant improvement from the second week of active treatment onwards to endpoint . The main side-effects were different from the usual side-effects in selective serotonin reuptake inhibitors ( SSRIs ) ( initial drowsiness , weight gain and pain in the legs ) . The results of this open label study in panic disorder suggest that mirtazapine seems to be a fast and effective treatment alternative for SSRIs in panic disorder", "OBJECTIVE To compare the long-term efficacy of venlafaxine extended release ( ER ) with placebo in preventing panic disorder relapse in out-patient treatment responders . METHOD Out patients aged > or = 18 years who met Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria for panic disorder with or without agoraphobia for at least the previous 3 months , with > or = 6 full symptom panic attacks in the 2 weeks prior to screening and > or = 3 in the 2 weeks before baseline and a Clinical Global Impressions-Severity of Illness rating > or = 4 at screen were eligible to participate . Out patients received flexible-dose ( 75 - 225 mg/day ) venla-faxine ER for 12 weeks . Treatment responders were r and omly assigned to venlafaxine ER or placebo for 26 weeks . Criteria for response were time to relapse during double-blind treatment , defined as > or = 2 full symptom panic attacks per week for 2 consecutive weeks or discontinuation due to loss of effectiveness , was evaluated using Kaplan-Meier survival analysis . The study was conducted between December 2001 and August 2003 . RESULTS The intent-to-treat population had 291 patients in the open-label phase and 169 in the double-blind phase ( placebo , N = 80 ; venlafaxine ER , N = 89 ; mean daily dose 165 - 171 mg ) . Time to relapse was significantly longer with venlafaxine ER than placebo ( p panic attack treatment efficacy , quality of life , and disability were significantly better with venlafaxine ER than placebo ( p Venlafaxine ER was safe , well tolerated , and effective in preventing relapse in out patients with panic disorder", "INTRODUCTION Individuals with anxiety disorders often remain symptomatic despite treatment with a first-line pharmacologic agent . More research examining pharmacotherapy augmentation strategies to improve outcomes is needed . METHODS In an 8-week , open-label , prospect i ve augmentation study , we examined the efficacy and tolerability of the novel antipsychotic agent aripiprazole for adult out patients with generalized anxiety disorder ( n=13 ) or panic disorder ( n=10 ) who remained symptomatic despite treatment for at least 8 weeks with an adequate ( or maximally tolerated ) dose of typical pharmacotherapy . RESULTS Aripiprazole augmentation was associated with a significant reduction in Clinical Global Impressions-Severity scores ( paired t=4.41 , df=22 , P sample of 23 individuals . Three subjects ( 13 % ) discontinued due to sedation , chest discomfort , and restlessness , respectively . CONCLUSION These data provide preliminary evidence that aripiprazole may be a useful augmentation strategy for individuals with generalized anxiety disorder or panic disorder who show a limited response to initial pharmacotherapy", "INTRODUCTION There is evidence that a decreased GABAergic tone plays a role in the pathophysiology of panic disorder ( PD ) . Selective GABAergic treatment has been suggested as a new therapeutic strategy in PD . In this pilot- study anxiolytic effects of the GABA reuptake inhibitor tiagabine ( TGB ) were investigated in PD . METHODS A total of 19 patients were treated with TGB ( n=10 ) or placebo ( n=9 ) for 4 weeks . PAS , HAM-A , and CGI ratings were administered every week . To further assess specific antipanic activity , panic challenges with CCK-4 were carried out in single subjects . RESULTS Although there was a significant reduction of clinical rating scores over time , no differences were detected between the groups . However , during challenge experiments TGB treated subjects showed decreased sensitivity to CCK-4 . DISCUSSION Whereas tiagabine did not show beneficial effects on clinical symptoms in PD compared to placebo , results of challenge experiments suggest effects of TGB on sensitivity to experimentally induced panic", "In a recent study , the authors suggested that tachycardia , dry mouth , and sweating continued to burden patients with panic disorder with agoraphobia who have shown marked and stable response to 6 months of imipramine treatment at the fixed , weight-adjusted dose of 2.25 mg/kg/day . Although sexual dysfunction and weight gain were not a significant burden in that study , they are important problems in long-term treatment with antidepressant drugs . In the present study , in the context of a r and omized , double-blind , placebo-controlled , 1-year discontinuation and maintenance study of 53 patients with panic disorder with agoraphobia who respond to imipramine , the authors examine the extent and the specificity of these five side effects of imipramine maintenance using data at pretreatment , at the end of 24 weeks of open imipramine treatment ( or month 0 of r and omization ) , and at months 2 , 4 , 6 , 8 , 10 , and 12 of r and omized treatment . Hierarchical linear modeling and repeated measures of analyses of variance in sub sample s of completers confirmed that dry mouth , sweating , and increased heart rate constitute a significant and specific enduring burden of imipramine maintenance treatment . The data also revealed that weight gain is a significant and specific side effect of 1-year imipramine maintenance treatment ; however , the likelihood of reporting sexual dysfunction decreased over time , with no difference between the placebo and imipramine maintenance conditions . The results are discussed in the context of previous studies of imipramine side effects in the management of depression and the available literature of sexual and weight side effects of antidepressant medications in the treatment of anxiety disorders", "In this report , which is an up date of a guideline published in 2002 ( B and elow et al. 2002 , World J Biol Psychiatry 3:171 ) , recommendations for the pharmacological treatment of anxiety disorder , obsessive-compulsive disorder ( OCD ) and post-traumatic stress disorder ( PTSD ) are presented . Since the publication of the first version of this guideline , a substantial number of new r and omized controlled studies of anxiolytics have been published . In particular , more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs . The recommendations , developed by the World Federation of Societies of Biological Psychiatry ( WFSBP ) Task Force for the Pharmacological Treatment of Anxiety , Obsessive-Compulsive and Post-traumatic Stress Disorders , a consensus panel of 30 international experts , are now based on 510 published r and omized , placebo- or comparator-controlled clinical studies ( RCTs ) and 130 open studies and case reports . First-line treatments for these disorders are selective serotonin reuptake inhibitors ( SSRIs ) , serotonin-noradrenaline reuptake inhibitors ( SNRIs ) and the calcium channel modulator pregabalin . Tricyclic antidepressants ( TCAs ) are equally effective for some disorders , but many are less well tolerated than the SSRIs/SNRIs . In treatment-resistant cases , benzodiazepines may be used when the patient does not have a history of substance abuse disorders . Potential treatment options for patients unresponsive to st and ard treatments are described in this overview . Although these guidelines focus on medications , non-pharmacological were also considered . Cognitive behavioural therapy ( CBT ) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders , OCD , and PTSD to support them being recommended either alone or in combination with the above medicines", "Serotonergic mechanisms have been implicated in panic disorder , and several preliminary studies suggest that fluvoxamine , a selective serotonin reuptake inhibitor ( SSRI ) , is helpful in its treatment . This 8-week double-blind parallel-group study compared fluvoxamine with a placebo in 188 patients with DSM-III-R defined panic disorder with or without agoraphobia . Efficacy assessment s included a Daily Panic Attack Inventory , the Sheehan Disability Scale , the Clinical Anxiety Scale and the Clinical Global Impression Scale . When compared with the placebo , fluvoxamine produced highly significant improvements in most measures of the frequency and severity of panic disorder and in the more global aspects of disability and distress . Significant improvement was evident as early as week 1 for some panic variables . Fluvoxamine is a potent anti-panic agent with a relatively rapid onset of action", "BACKGROUND Tricyclic antidepressants and selective serotonin reuptake inhibitors ( SSRIs ) as well as benzodiazepines have been shown to be effective for the treatment of panic disorder . The introduction of SSRIs has enabled a greater underst and ing of the role of serotonin in the etiology of panic disorder ; however , the role of norepinephrine has been more challenging to ascertain . The aim of this study was to determine the efficacy and tolerability of reboxetine , a novel selective norepinephrine reuptake inhibitor , in patients with panic disorder with and without agoraphobia . METHOD Eighty-two patients ( aged 18 - 65 years ) with DSM-III-R panic disorder , with or without agoraphobia , were r and omly assigned to receive 6 to 8 mg/day of reboxetine ( 42 patients ) or placebo ( 40 patients ) for 8 weeks in this placebo-controlled , parallel-group , double-blind clinical trial . RESULTS Of the 82 patients enrolled in the trial , 75 were considered in the analysis ( 37 patients in the reboxetine group and 38 patients in the placebo group ) . At last assessment , there was a significant reduction in the mean number of panic attacks ( range , 9.3 - 1.2 ) and phobic symptoms ( range , 8.1 - 3.2 ) in the reboxetine group compared with the placebo group ( ranges , 8.5 - 5.8 and 7.7 - 5.2 , respectively ; p Hamilton Rating Scale for Depression , Hopkins Symptom Checklist-90 , and Sheehan Disability Scale scores were also greater in the reboxetine group compared with the placebo group . Adverse events reported more frequently with reboxetine than placebo included dry mouth ( 36 % vs. 16 % ) , constipation ( 27 % vs. 22 % ) , and insomnia ( 26 % vs. 22 % ) . CONCLUSION Reboxetine was effective and well tolerated in the treatment of panic disorder", "Fifteen patients with panic disorder participated in a 12-week treatment trial with open-label nefazodone . Nefazodone was well-tolerated with minimal side effects ; none of the patients reported sexual dysfunction , and only one patient experienced weight gain . Although the response rate was lower than that found with most other antipanic medications , given its favorable side effect profile , nefazodone may be a good alternative for patients apprehensive about potential adverse drug reactions", "BACKGROUND Serotonin Selective Re-uptake Inhibitors ( SSRIs ) are the drugs of choice for treating panic disorder ( PD ) . In vitro studies have shown different pharmacodynamic profiles for SSRIs , but their clinical relevance is still unknown . Paroxetine , the SSRI with the strongest serotonergic effect , also shows significant cholinergic and noradrenergic activities . In this class of drugs , citalopram is the most selective for serotonin . We compared these two drugs and their effectiveness and tolerability in a sample of patients with PD in a two-month treatment course . METHOD Fifty-eight patients with PD were r and omly assigned to either the paroxetine or the citalopram treatment group in a single-blind , r and omized design . Each patient was assessed at days 0 , 7 and 60 by the Panic Associated Symptoms Scale ( PASS ) , the Sheehan Disability Scale ( SDS ) and the Fear Question naire ( FQ ) . Primary outcome measures were the percentage of patients free of panic attacks , anticipatory anxiety and phobic avoidance in the last week of the trial and the percentage of good responders , as defined by a reduction of at least 50 % from baseline of both PASS and SDS global scores at day 60 . RESULTS At day 60 , 86 % of patients receiving citalopram and 84 % of those receiving paroxetine responded well to treatment . No significant differences between the two drugs were found . Both were well tolerated , although sexual side effects and weight gain were frequent . Anticipatory anxiety decreased significantly after the first week of treatment , and no initial worsening in the panic attacks was observed . CONCLUSION Paroxetine and citalopram show similar anti-panic properties and a good tolerability profile . Our results support evidence that the serotonergic system plays a significant role in the anti-panic properties of these two SSRIs", "The effect of a short treatment ( 7 days ) with citalopram on the reactivity to inhalations of 35 % CO 2 and 65 % oxygen and on clinical symptomatology was investigated in 15 patients with panic disorder who had a positive response to 35 % CO 2 inhalation . An open study design was applied . On day 0 , before starting drug treatment , and after 1 week of treatment , each patient underwent the 35 % CO 2 challenge , and clinical symptomatology was evaluated with psychometric scales . The results showed a significant reduction of CO 2 reactivity and of scores on the anticipatory anxiety subscale of Panic Associated Symptoms Scale . These results confirm that the serotonergic system plays an important role in the modulation of CO 2 hyperreactivity and suggest an early anxiolytic effect of citalopram in patients who have panic disorder and are hyperreactive to CO 2", "OBJECTIVE Several classes of medications have demonstrated efficacy in panic disorder , but direct comparison of 2 proven treatments is still uncommon . The purpose of this study was to compare sertraline and paroxetine in the acute treatment of panic disorder . METHOD Adult out patients with panic disorder with or without agoraphobia ( DSM-IV and ICD-10 criteria ) were r and omly assigned in double-blind fashion to 12 weeks of treatment with flexible doses of sertraline ( titrated up to 50 - 150 mg/day ; N = 112 ) or paroxetine ( titrated up to 40 - 60 mg/day ; N = 113 ) . Patients were then tapered off medication over 3 weeks . The primary analysis was a noninferiority analysis of Panic and Agoraphobia Scale ( PAS ) scores . Secondary measures included panic attack frequency and the Clinical Global Impressions-Improvement scale ( CGI-I ) ( with responders defined as those with a CGI-I score Sertraline and paroxetine were associated with equivalent levels of improvement on the PAS total score , as well as on all secondary outcome measures . Eighty-two percent of patients taking sertraline versus 78 % of those taking paroxetine were CGI-I responders at endpoint . Numerically more patients on paroxetine treatment compared with sertraline treatment discontinued due to adverse events ( 18 % vs. 12 % ; NS ) , and a significantly higher proportion of paroxetine patients showed > or = 7 % weight gain ( 7 % vs. proportion of panic-free patients increased by 4 % with sertraline but decreased by 11 % with paroxetine ( p Sertraline and paroxetine had equivalent efficacy in panic disorder , but sertraline was significantly better tolerated and was associated with significantly less clinical worsening during taper than paroxetine", "Our objective was to explore the dose-response relationship in patients with panic disorder and social anxiety disorder comorbidity ( DSM-IV ) . After 1 week of no-drug washout , 36 such patients were assigned to a double-blind controlled comparison of the effects of 30 mg and 60 mg of tranylcypromine , and were followed up for 12 weeks . The main instrument used to measure the number of panic attacks was the Sheehan Panic and Anticipatory Anxiety Scale . The primary outcome measure for social anxiety disorder symptoms was the mean change from baseline in the Liebowitz Social Anxiety Scale ( LSAS ) . After 12 weeks of treatment , panic attacks were reduced 69.6 % from baseline in the 30-mg group ( n=19 ) compared with a 74.8 % reduction in the 60-mg group ( n=17 ) . Twelve patients ( 70.6 % ) of the higher dose group and 14 patients ( 68.4 % ) of the lower dose were completely free of panic attacks . There was no difference in efficacy between the tranylcypromine groups in the panic disorder symptoms . The 60-mg dose was more efficacious as measured by the LSAS scores , showing a significant difference in relation to the lower group . Mean change from baseline in LSAS total score ( mean+/-SD ) for 30-mg group was 17.9+/-14.7 and for the 60-mg group was 35.0+/-14.8 . The social anxiety symptom scale showed a two-fold greater change with the 60-mg dose , and the 30-mg dose group could be considered the equivalent of a placebo control group . Tranylcypromine--60 mg daily -- was found effective in the treatment of panic disorder and social anxiety disorder comorbidity" ]	4118912c-06ff-11f0-808a-c43d1ab1c353
CONTEXT While the main focus of a meta- analysis is often to assess the effectiveness of a particular intervention in managing or curing a specific condition , there exists a substantial amount of information within published systematic review s that could be used to assess the validity of a generic hypothesis about the effectiveness of an intervention across a range of different but related conditions . OBJECTIVE To systematic ally search for and then collate the results of meta-analyses for the effectiveness of antibiotic prophylaxis in preventing postoperative wound infection across various types of surgery in order to assess generic hypotheses about the effectiveness of this intervention in surgery as a whole . With the relative risk of wound infection used as the measure of clinical effectiveness , the hypotheses to be assessed were first that antibiotic prophylaxis would be an effective intervention for preventing wound infection over a broad range of different surgical procedures , and second that there would be a substantial difference in the effectiveness of antibiotic prophylaxis between " clean " and " contaminated " surgical procedures . DATA SOURCES Medline and the Cochrane Data base of Systematic Review s. STUDY SELECTION Eligible meta-analyses were meta-analyses published between 1990 and 2006 of r and omized controlled trials that looked at the effectiveness of prophylactic antibiotics versus no antibiotic or placebo in preventing postoperative wound infections . DATA EXTRACTION Independent data extraction by multiple observers . RESULTS The first hypothesis was strongly supported by the data as evidence d by the fact that the estimates of the relative risk of infection for the 23 types of surgery that were included in the study were all less than 1 . However , there was no real evidence supporting the second hypothesis that the relative risk of wound infection would substantially vary over different levels of surgery cleanliness . CONCLUSION : As well as antibiotic prophylaxis being a generally effective intervention for preventing postoperative wound infection , the level of this effectiveness would appear to be reasonably independent of what type of surgery is being considered . Therefore , the general prevailing attitude that antibiotic prophylaxis should be assumed to be ineffective unless its effectiveness has been experimentally proven beyond doubt for the specific type of surgery being considered , perhaps should be revised . In particular , perhaps a sensible philosophy would be to assume that antibiotic prophylaxis is effective in reducing the risk of wound infection for all types of surgery , even ones where no clinical trial data exists and make exceptions to this rule if , for certain types of surgery , it can be proved to the contrary	[ "BACKGROUND The efficacy of prophylactic antibiotics in fracture surgery remains controversial for lack of well-documented prospect i ve studies . We report here the findings of the Dutch Trauma Trial , a prospect i ve , r and omised , double-blind , placebo-controlled study of antibiotic prophylaxis in the primary operative treatment of limb fractures . Ceftriaxone was chosen because of its pharmacokinetic profile , including high serum levels , high tissue penetration , and long elimination half-life , makes it suitable for single-dose prophylaxis . METHODS Patients aged 18 years or more , attending one of fourteen Dutch centres for acute treatment of closed fractures , were r and omly allocated to a single preoperative dose of ceftriaxone 2 g or placebo , and evaluated for development of wound infection and nosocomial infection at 10 days , 30 days , and 120 days . To assess the effects of drop-outs and withdrawals , best-case and worst-case analyses were performed . FINDINGS A total of 2195 patients were included . The incidence of superficial and deep wound infections after placebo was 8.3 % , compared with 3.6 % in the ceftriaxone group ( p rate of nosocomial infection in the first month was 10.2 % with placebo and 2.3 % with ceftriaxone ( p Gram-positive bacteria were found in 74.5 % of wound infections and 13.4 % of nosocomial infections . INTERPRETATION Adequate single-dose prophylaxis with a long-acting broad-spectrum antibiotic substantially reduces the incidence of wound infection and early nosocomial infection after surgery for closed fractures", "Every word to utter from the writer involves the element of this life . The writer really shows how the simple words can maximize how the impression of this book is uttered directly for the readers . Even you have known about the content of r and omization tests so much , you can easily do it for your better connection . In delivering the presence of the book concept , you can find out the boo site here", "Antibiotic prophylaxis in closed fractures is cost-effective if the risk of a deep infection is reduced by 0.25 % . This control study was undertaken to assess the cost-effectiveness of prophylaxis of postoperative infections after surgical treatment of closed fractures . The costs for 16 patients with infections ( 8 with deep infections , 8 with superficial infections ) were investigated and compared with the costs for 16 similar but non-infected patients with special reference to length of hospital stay , antibiotics and surgery . The data were collected from the trauma department of the University Hospital of the Free University in Amsterdam . Costs in the group of 8 patients with superficial wound infection were not substantially higher than those for their non-infected controls . The occurrence of a deep infection meant costs an average of DFL 35,224 higher than an uneventful postoperative course . On the basis of these results , antibiotic prophylaxis of postoperative wound infections is cost-effective if it reduces the risk of deep wound infections by about 0.25 %" ]	41189168-06ff-11f0-808a-c43d1ab1c353
Objective : To give a systematic review of clinical measurement scales used to assess trunk performance after stroke . Data sources : The data bases CINAHL , Cochrane , Pedro and PubMed were search ed with the terms ` sitting balance ' plus ` stroke ' and ` trunk ' plus ` stroke ' mentioned in the title or abstract . Data bases were search ed from inception to January 2006 . Review methods : All articles were selected which reported or included a clinical measure of trunk performance used in an adult stroke population . Reference lists were search ed as secondary sources of articles . Results : A total of 458 articles result ed from the data base search . Thirty-two articles were eligible for inclusion . Earlier studies mentioned ordinal single items or a combination of items which are part of a larger scale used to assess sitting balance as a derived measure of trunk performance . Three clinical tools were available which specifically evaluated trunk performance after stroke ; the Trunk Control Test and two Trunk Impairment Scales . Conclusion : Ordinal single items or subscales of existing larger scales lack a systematic evaluation of psychometric characteristics . Both Trunk Impairment Scales have been extensively examined . A comparative study assessing psychometric properties of the Trunk Control Test and two Trunk Impairment Scales could determine which should be the measure of choice when assessing trunk performance after stroke	[ "To test the hypothesis that recovering stroke patients with initially good sitting balance or those who develop good sitting balance during rehabilitation have better Barthel Index-based functional assessment outcomes than recovering stroke patients with poor sitting balance , we prospect ively studied 24 of 25 consecutive stroke patients admitted to a tertiary-care hospital rehabilitation unit . Sitting balance , a prerequisite for most functional activities , was scored using a four-point scale evaluating static and dynamic sitting balance on admission to the rehabilitation unit and weekly until discharge . Functional status was assessed using the Barthel Index 4 or 12 weeks after the stroke . We found a strong positive correlation between Barthel Index score and each weekly sitting balance score . Multiple evaluations over time identified those patients whose sitting balance improved during rehabilitation in our unit ; after grouping the patients into those with normal , improved , and poor sitting balance , we found a significant difference in the Barthel Index scores among the three groups . The group of patients whose sitting balance improved had higher Barthel Index scores than the group whose sitting balance did not improve . Ongoing evaluation of sitting balance can be helpful in anticipating functional status at discharge in stroke patients undergoing comprehensive rehabilitation", "This study was undertaken to determine muscle strength of trunk flexion-extension in hemiplegic patients after stroke compared with that of normal controls . The design consisted of a nonr and omized control trial in a secondary care setting ( a rehabilitation unit at a hospital facility ) . The subjects included 25 post-stroke male hemiplegic patients and 25 male healthy controls . The maximal peak torques of trunk flexion-extension at angular velocities of 0 degrees ( isometric contraction ) , 60 degrees , 120 degrees , and 150 degrees/s were measured by using an isokinetic dynamometer ( Cybex Trunk Extension-Flexion Unit , Cybex , Ronkonkoma , NY ) . Peak torque of trunk flexion and extension in hemiplegic patients was significantly smaller than that of healthy controls ( P 0.05 ) . The weakness of trunk flexion-extension muscles in hemiplegic patients might be accounted for by the bilateral innervation from the motor cortex , the insufficient use of high threshold motor units , and disuse atrophy", "Background and Purpose — Prediction of activities of daily living ( ADL ) functions at an early stage after a stroke is critical because it enables clinicians to set treatment programs and goals . The objective of this study was to assess the relationship between trunk control at an early stage and comprehensive ADL function ( as assessed by combining basic ADL and instrumental ADL [ IADL ] ) in patients at 6 months after stroke . Methods — A total of 169 stroke patients participated in this prospect i ve study . Trunk control was measured with the use of the trunk control items of the Postural Assessment Scale for Stroke Patients ( PASS-TC ) . In addition to the PASS-TC score , age , sex , type of stroke , side of hemiparesis , urinary incontinence , limb paresis ( measured by the Fugl-Meyer motor test ) , balance ( measured by the Fugl-Meyer balance test ) , and basic ADL ( measured by the Barthel Index ) were also selected as predictor variables . These variables were assessed at 14 days after stroke or earlier . The Barthel Index and Frenchay Activities Index ( measuring IADL ) were administered at 6 months after stroke . The sum of the st and ardized Barthel Index and st and ardized Frenchay Activities Index scores was used to assess comprehensive ADL function . Results — Multivariable stepwise linear regression analysis showed that PASS-TC score , age , Fugl-Meyer motor test score , and Barthel Index score ( listed by the order of forward selection ) were the strongest predictors of comprehensive ADL function . These results were internally vali date d with the use of the bootstrap resampling technique . The PASS-TC score alone accounted for 45 % of the variance in predicting comprehensive ADL function . Results also indicated that the PASS-TC score had slightly more power in predicting comprehensive ADL function than either the Fugl-Meyer motor test score or Barthel Index score . Conclusions — The findings of this study provide strong evidence of the predictive value of trunk control on comprehensive ADL function in stroke patients . The results imply that early assessment and management of trunk control after stroke should be emphasized", "BACKGROUND AND PURPOSE The trunk control items of the Postural Assessment Scale for Stroke Patients ( PASS-TC ) have been proposed for use in examining patients with stroke . The purpose of this study was to examine the discriminative and predictive validities and the evaluative properties of the PASS-TC at 14 , 30 , 90 , and 180 days after stroke onset . SUBJECTS AND METHODS A total of 269 patients with stroke participated in this prospect i ve study . The PASS-TC was administered at the 4 time points after stroke onset . The distributions of the PASS-TC scores were used to determine the discriminative ability to distinguish between individuals at the 4 time points . A comprehensive activities of daily living ( CADL ) measure was administered 1 year after stroke onset as an external criterion for examining the predictive ability of the PASS-TC . Changes in PASS-TC scores between the intervals of 14 to 30 , 30 to 90 , and 90 to 180 days after stroke onset were used to examine the evaluative properties of the measure . RESULTS The PASS-TC scores exhibited differences between the patients with disability and the patients without disability at the 4 time points . The scale , however , showed a notable ceiling effect at the 4 time points ( > 30 % of the subjects ) , indicating a limited discriminative ability between individuals . The scores of the PASS-TC at the 4 time points were moderately correlated with the CADL scores at 1 year after stroke onset ( Spearman rhof.5 ) , evidence of its predictive validity . The responsiveness of the PASS-TC was moderate at 14 to 30 days after stroke ( st and ardized response mean [SRM]=.65 ) and limited at 30 to 90 and 90 to 180 days after stroke ( SRM=.42 and .02 , respectively ) . DISCUSSION AND CONCLUSION The results provide evidence that the PASS-TC can predict CADL function at 1 year after a stroke , but the discriminative and evaluative abilities are limited over the first 6 months after a stroke . To promote the utility of the PASS-TC in stroke research , it will be necessary to reduce its ceiling effect and improve its evaluative ability", "The purpose of this study was to evaluate prospect ively the Trunk Control Test ( TCT ) correlation at admission to rehabilitation with length of stay , functional independence measure ( FIM ) , gait velocity , walking distance and balance measured at discharge in 28 hemiparetic patients . FIM and TCT were registered on admission . Outcome measures at discharge were : FIM , gait velocity , walking distance and balance assessed with the Berg Balance Scale and computerized posturography . TCT was significantly correlated with length of stay ( r = -0.722 ) , discharge FIM ( r = 0.738 ) , discharge motor FIM ( r = 0.723 ) , gait velocity ( r = 0.654 ) , walking distance ( p = 0.003 ) , centre of gravity symmetry r = 0.601 ) and Berg Balance Scale ( r = 0.755 ) . Initial TCT predicts the 52 % of the variation in length of stay and 54 % in the discharge FIM . The predictive value of a compound variable ( TCT and admission FIM ) reaches 60 % of the variation in length of stay and 66 % in the FIM at discharge", "Karatas M , Çetin N , Bayramoglu M , Dilek A : Trunk muscle strength in relation to balance and functional disability in unihemispheric stroke patients . Am J Phys Med Rehabil 2004;83:81–87 . Objective To evaluate trunk muscle strength in unihemispheric stroke patients and to assess how it relates to body balance and functional disability in this patient group . Design This prospect i ve case-comparison study investigated isometric and isokinetic reciprocal trunk flexion and extension strength at angular velocities in 38 unihemispheric stroke patients and 40 healthy volunteers . The Berg balance scale was used to assess balance and stability , and the FIM ™ instrument was used to evaluate functional disability in the patient group . Patients were evaluated as soon as they were able to st and long enough for testing . Results Peak torque values for trunk flexion and extension were lower in the stroke patients than in the controls . The differences were significant for trunk flexion and for trunk extension . In both groups , peak torque values for trunk flexors were greater than peak torque values for trunk extensors . There was a significant positive correlation between trunk muscle strength and Berg balance scale score at discharge . Trunk muscle strength was not correlated with FIM total score or FIM motor score , but the locomotion-transfers FIM subscore at discharge was positively correlated with trunk muscle torque values , except for isometric extension . Conclusion The findings indicate trunk flexion and extension muscle weakness in unihemispheric stroke patients , which can interfere with balance , stability , and functional disability", "OBJECTIVES To study electromyographic characteristics of anticipatory postural adjustment in axial and lateral , posterior and anterior trunk muscles during the performance of upper- and lower-limb flexion tasks , in subjects with hemiparesis after stroke and to determine the relationship between anticipatory activity and subjects ' motor and functional status . DESIGN A nonr and omized control study . SETTING Geriatric rehabilitation center in Israel . PARTICIPANTS Fifty poststroke hemiparetic patients and 30 healthy control subjects . INTERVENTION Electromyographic activity of the lumbar erector spinae and of the latissimus dorsi muscles was recorded bilaterally during flexion of either arm and from the 2 rectus abdominis and obliquus externus muscles during flexion of either hip . MAIN OUTCOME MEASURES Muscles ' onset latency , cross-correlation values between the temporal activation profile of corresponding pairs and between ipsilateral muscular pairs , symmetry in activation magnitude of corresponding muscles , and relation between electromyographic activity and motor and functional performance RESULTS Onset latencies of trunk muscles were partially delayed in the patients with longest hindrance displayed by the erector spinae ipsilateral to the flexing arm ( P Temporal synchronization between pertinent muscular pairs was lower in the patients than in the healthy subjects , with significant group differences ( P Activation of the corresponding lateral trunk muscles in the patients was significantly less symmetrical than in the controls ( P limb flexion was associated with increased activity in the ipsilateral lateral trunk muscle . The erector spinae muscle in both groups and on both sides was more active on the contralateral side than on the ipsilateral side to the flexing arm . The reduced activity level in trunk muscles on the paretic body side was associated with deficiencies in motor and functional abilities . CONCLUSIONS Major impairments in the activity of trunk muscles in hemiparetic subjects were manifested in the reduced activity level of the lateral trunk muscles , in delayed onset , and in reduced synchronization between activation of pertinent muscular pairs . These problems were associated with motor and functional deficits and warrant specific consideration during physical rehabilitation of post stroke hemiparetic patients", "Objective : To examine the scalability of the Rivermead Motor Assessment ( RMA ) with nonacute stroke patients in the community . Design : This was a prospect i ve study of the patients after discharge from hospital . All subjects were assessed on the RMA at six and 12 months after discharge home from hospital . Coefficients of scalability and reproducibility were calculated for each of the three sections of the RMA at each assessment . Subjects : Subjects were nonacute stroke patients aged 65 years and over , nonacute stroke patients aged under 65 years , and a selected group of those aged under 65 years . Results : Only the items in the gross function section met scaling criteria with nonacute strokes in both age groups , which suggests that the items in this section were in appropriate order of difficulty . The items in the leg and trunk section were not in hierarchical order and were in fact closer to scaling if the present order were reversed . Conclusions : The clinical and research value of the RMA , as an ordered scale , are question ed . Changes in treatment styles and philosophies may mean that some of the items themselves are out- date", "OBJECTIVES To evaluate test-retest reliability of sitting balance measures in healthy subjects and individuals with hemiparesis secondary to stroke , to evaluate the ability of the balance measures and Functional Independence Measure ( FIM ) to document changes over time , and to compare changes in the balance measures and FIM to each other . METHOD Six nonpatient subjects were evaluated for test-retest reliability . Fourteen subjects with hemiparesis were tested every 2 weeks during their hospitalization on their ability to lean to either side , lean forward , and maintain a symmetrical posture . Maximum displacement was recorded using the Balance System . FIM scores were obtained for each testing session . RESULTS Test-retest reliability for nonpatient subjects was high and for patients was moderate to high . Leaning forward and to the paretic side showed the greatest number of correlations with the FIM scores . All of the FIM scales and the forward lean measure documented progress . CONCLUSIONS The protocol developed to test sitting balance , using the Balance System , seems appropriate for use with patient population s. The ability to lean maximally to either side or forward or sit symmetrically is not strongly related to function", "Fujiwara T , Liu M , Tsuji T , Sonoda S , Mizuno K , Akaboshi K , Hase K , Masakado Y , Chino N : Development of a new measure to assess trunk impairment after stroke ( Trunk Impairment Scale ) : Its psychometric properties . Am J Phys Med Rehabil 2004;83:681–688 . Objective : The purpose of this study was to investigate reliability , validity , internal structure , and responsiveness of our newly developed Trunk Impairment Scale ( TIS ) for patients with stroke . Design : A total of 73 patients with stroke participated in this prospect i ve study . Interrater reliability ( weighted kappa statistics ) , content validity ( principal component analysis ) , concurrent validity ( Spearman 's rank correlation with the Trunk Control Test ) , predictive validity ( prediction of discharge FIM ™ scores ) , and responsiveness ( st and ardized response mean values ) were examined . Internal consistency and item difficulties were analyzed with Rasch analysis . Results : The weighted kappa of each TIS item ranged from 0.66 to 1.0 . Principal component analysis revealed that the TIS measured a domain similar to the Stroke Impairment Assessment Set trunk items but different from the Stroke Impairment Assessment Set motor and visuospatial items . The TIS correlated with the Trunk Control Test ( r = 0.91 ) . To predict discharge FIM motor scores , addition of the TIS as one of the predictors to age , time from onset , and admission FIM score increased the adjusted R2 from 0.66 to 0.75 . With Rasch analysis , the misfit was acceptable , except for the abdominal muscle strength item . The difficulty patterns were similar at admission and discharge , except for the abdominal muscle strength item . The responsiveness of the TIS was satisfactory and comparable with that of the Trunk Control Test ( st and ardized response mean values , 0.94 and 1.06 ) . Conclusions : Our newly developed TIS is reliable , valid , and responsive for use in stroke outcome research", "This study was undertaken to determine whether the direction of trunk rotation would have any effect on trunk muscle performance of post-stroke hemiplegic patients . The design consisted of a nonr and omized control trial in a setting of secondary care ( rehabilitation unit at hospital facility ) . The subjects included 65 hemiplegic patients ( 50 males ) and age-matched 80 healthy controls ( 38 females ) . Isokinetic trunk rotatory muscle performance at angular velocities of 60 , 120 , and 150 degrees per second was measured by using an isokinetic dynamometer ( Cybex Torso Rotation Unit ) . There were no significant differences in the peak torque and best work between the right and left directions of the trunk rotation in the hemiplegic patients or in healthy controls , regardless of the gender of the subjects ( paired t test , P > 0.05 ) . The muscle performance of the hemiplegic patients was significantly lower than that of the controls for both genders ( t test , P trunk rotatory muscle performance , although the performance itself was slightly decreased", "Purpose . The Trunk Impairment Scale ( TIS ) is a st and ardized scale to evaluate the trunk function in stroke patients . It was the aim of this study to determine the discriminant ability of the TIS by comparing stroke patients with healthy individuals . Further , the variables that had an influence on obtaining a high score on the TIS in healthy subjects were examined . Method . Forty stroke patients and 40 age- and sex-matched healthy individuals were included in the study . TIS scores from the stroke patients and healthy individuals were compared using the Wilcoxon ranked sum test . Results . Sub-scale and total TIS scores showed significant differences between stroke patients and healthy individuals ( P high score on the TIS . Conclusions . The TIS discriminates between stroke patients and healthy individuals . A submaximal score on the TIS was found in 45 % of the healthy subjects suggesting that a lower score on the TIS still indicates normal trunk function and full participation in daily life", "OBJECTIVE To examine the scalability of the Rivermead Motor Assessment with hospitalized acute stroke patients . DESIGN This was a prospect i ve study of hospitalized stroke patients . SUBJECTS Fifty-one selected stroke patients , including those over the age of 65 , were assessed at one , three and six weeks post-stroke using the Rivermead Motor Assessment . Coefficients of scalability and reproducibility were calculated for each of the three sections of the Rivermead Motor Assessment at each assessment . RESULTS The items in the gross function and arm sections met scaling criteria at all three assessment s which meant that they were in appropriate order of difficulty . There was an overall increase in the proportion of subjects passing each item at successive assessment s , suggesting that patients in the study were recovering . The leg and trunk section did not meet scale criteria with these acute stroke patients . CONCLUSIONS We recommend that only the gross function and arm sections should be used as hierarchical scales with selected acute stroke patients . The leg and trunk section should only be used as an assessment checklist" ]	411891a4-06ff-11f0-808a-c43d1ab1c353
OBJECTIVES The purpose of this paper was to review current literature on the clinical effectiveness of contemporary adhesives when used to restore cervical non-carious class-V lesions . Restoration retention in function of time was recorded in order to find out if adhesives with a simplified application procedure are as clinical ly effective as conventional three-step adhesives . DATA SOURCES Literature published from January 1998 up to May 2004 was review ed for university-centred clinical trials that tested the clinical effectiveness of adhesives in non-carious class-V lesions . Restoration-retention rates per adhesive reported in peer- review ed papers as well as IADR-AADR abstract s and ConsEuro abstract s were included and depicted as a function of time in graphs for each of the five adhesive classes ( three- and two-step etch- and -rinse adhesives , two- and one-step self-etch adhesives , and glass-ionomers ) . The guidelines for dentin and enamel adhesive material s advanced by the American Dental Association were used as a reference . Per class , the annual failure rate ( % ) was calculated . Kruskal-Wallis analysis and Dwass-Steel-Chritchlow-Fligner pairwise comparisons were used to determine statistical differences between the annual failure percentages of the five adhesive categories . RESULTS Comparison of retention of class-V adhesive restorations as a measure to determine clinical bonding effectiveness of adhesives revealed that glass-ionomers most effectively and durably bond to tooth tissue . Three-step etch- and -rinse adhesives and two-step self-etch adhesives showed a clinical ly reliable and predictably good clinical performance . The clinical effectiveness of two-step etch- and -rinse adhesives was less favourable , while an inefficient clinical performance was noted for the one-step self-etch adhesives . SIGNIFICANCE Although there is a tendency towards adhesives with simplified application procedures , simplification so far appears to induce loss of effectiveness . Clinical performance can be correlated with , and predicted by , appropriate types of laboratory study	[ "OBJECTIVE This controlled clinical trial evaluated the 5-year clinical performance of a self-etching primer system including selective enamel-etching with phosphoric acid and a one-bottle adhesive system . METHODS Seventy-two non-carious cervical lesions in 8 patients ( 4 male and 4 female ) with a mean age of 61.3 years ( range 45 - 78 ) participated in the study . An enamel bevel was placed and dentin lightly ground , and cavities restored with clearfil liner bond II ( LB ) or single bond ( SB ) in conjunction with a hybrid resin composite ( Clearfil AP-X ) . In the case of 27 cavities for LB , the enamel was pretreated with 37 % phosphoric acid for 10 s. Each patient received both types of restoration , which were distributed on a r and om basis . All restorations ( 37 restorations for LB and 35 restorations for SB ) were placed by one dentist . The restorations were evaluated blind after 5 years using modified USPHS criteria . The data were statistically analyzed using the Fisher 's exact test . RESULTS All but one restoration ( which was replaced by a crown after the 2-year recall ) were evaluated after 5 years . 100 % retention rates were recorded for both restorative groups . No caries was detected in association with any restorations . The only minor problem was marginal discoloration ; superficial and localized marginal discoloration occurred around 18 % of the restorations , and mainly at the dentin margin . There were no significant differences in the marginal integrity between the LB and SB groups . CONCLUSIONS Restorative material s used in this study demonstrated a good clinical effectiveness in the restoration of non-carious cervical lesions for 5 years", "This study evaluated the effect of the thickness of the adhesive resin layer of two commercially available resin bonding systems on bond strengths ( Single Bond and Liner Bond 2V ) . The adhesive of Single Bond contains ethanol and water as solvents and is applied using the moist-bonding technique . The adhesive of Liner Bond 2V contains no solvents and is applied after a self-etching primer treatment . Forty-six caries-free molars were ground flat to expose the dentin surface and polished with # 800-grit silicon carbide paper under running water . A vinyl tape punched with a 6 mm diameter hole was then placed on the dentin surface to demarcate the area for bonding . The thickness of the adhesive resin layer was varied by stacking an increasing numbers of vinyl tapes together . The teeth were r and omly divided into two groups and treated with either Clearfil Liner Bond 2V or Single Bond . They were further divided into subgroups according to the number of tapes placed on the dentin surface . After the bonding procedures the teeth were incrementally restored with Clearfil AP-X resin composite , building a 5 mm high crown to produce sufficient bulk for the microtensile bond test and stored in tap water at 37 degrees C for 24 hours . The teeth were then sectioned along their long axis into 0.7 mm thick slabs and trimmed for the microtensile bond test using a super-fine diamond bur . The thickness of the adhesive resin layer was then measured with a light microscope and the slabs tested in tension at a crosshead speed of 1 mm/minute . The results were subjected to statistical analysis by a one-way analysis of variance and linear regressions with 95 % confidence intervals . The thickness of the Clearfil Liner Bond 2V adhesive layer ranged from 5 mm-1500 mm , and for Single Bond , it varied from bond strengths increased significantly as the thickness of bonding layer increased ( p bond strengths of the Single Bond decreased significantly with increased thickness of the bonding layer ( p < 0.05 )", "This study evaluated the clinical performance and appearance of a resin-modified glass ionomer and a resin composite over one year . Thirty-seven pairs of restorations of Fuji II LC and Z250/Single Bond were placed in caries-free cervical erosion/abfraction lesions without tooth preparation . Restorations were clinical ly evaluated at baseline and 6 and 12 months , using modified Ryge/USPHS criteria . No significant difference ( p>0.05 ) was observed in performance of both material s , although retention of the Z250 restorations was below the minimum specified in the ADA Acceptance Program for Dentin and Enamel Adhesives . Little difference in the restorations ' appearance was observed", "This study evaluated the clinical performance of a self-etching adhesive for resin composites over one year . Thirty pairs of restorations of Pertac II , using the adhesive Prompt L-Pop , were placed in caries-free cervical erosion/abfraction lesions without tooth preparation . One of each pair was cured using \" soft-start \" polymerization , while the other was polymerized with high-intensity halogen light . Restorations were clinical ly evaluated at baseline , six and 12 months using modified Ryge/USPHS criteria . Although no significant difference ( p>0.05 ) was observed between the curing methods , adhesive performance was poor , with a 35 % loss of restorations overall", "Modern dental adhesive systems have improved the bond of restorative material s to mineralized tooth structures . The purpose of this study was to evaluate the clinical performance of composite restorations placed in abrasion and erosion lesions using the Clearfil Liner Bond dental adhesive system . Following ADA clinical guidelines for dentin and enamel adhesive material s , 62 facial class 5 smooth surface erosion or abrasion lesions with no undercuts and involving primarily root surfaces were restored in 25 adult male and female patients . The teeth were restored without preparations using Clearfil Liner Bond and Clearfil Photo Anterior composite resin . The clinical performance of the restorations was assessed by two examiners at baseline , 6 months , 1 , 2 , and 3 years using the following evaluative parameters : color match , marginal discoloration , and marginal integrity according to modified Ryge criteria ; the presence or absence of recurrent decay ; pre- and postoperative sensitivity ; and restoration failure due to loss of retention or other causes . At the end of 3 years , four of the 55 restorations remaining in the study failed due to lack of retention ( 92.7 % retention rate ) . The evaluations of the other clinical parameters demonstrated excellent performance by this system", "PURPOSE Acid-etched dentin has been described to easily collapse when it is dried with air after being rinsed with water under laboratorial \" ideal \" conditions . Manufacturers of modern dentin adhesives recommend leaving dentin moist , regardless of the solvent used in their proprietary dentin adhesives . Nevertheless , many clinicians still dry the cavity preparation after rinsing off the etching gel to check for the enamel frosted aspect . The None hypothesis to be tested in this clinical study was that drying dentin with air upon rinsing off the acid would not result in lower short-term retention rates than when the cavity was left visibly moist . MATERIAL S AND METHODS Upon Internal Review Board approval , thirty-five patients were enrolled in this study . A total of 128 restorations divided into four groups were inserted and evaluated at baseline : ( A ) Prime & Bond NT , an acetone-based adhesive , applied on moist dentin ; ( B ) Prime & Bond NT applied on dentin dried with air for 3 to 4 s ; ( C ) Single Bond , an ethanol- and water-based adhesive , applied on moist dentin ; ( D ) Single Bond applied on dentin dried with air for 3 to 4 s. A microfilled composite resin was used for all restorations . RESULTS At 6 months after initial placement , 119 restorations ( a 93 % recall rate ) were re-evaluated . Retention rates at 6 months were 97 % ( one failure ) for Single Bond/moist dentin and 100 % for the remaining three groups ; however , they were not significantly different ( retention rate vs dentin adhesive ; retention rate vs moisture ) . CONCLUSION Dentin substrate in noncarious lesions may be less sensitive to variations in dentin moisture than the \" ideal \" dentin substrate used under laboratory conditions", "OBJECTIVE The purpose of this study was to evaluate the performance of a filled ( OptiBond Solo ) and an unfilled ( Prime & Bond 2.1 ) \" one-bottle \" adhesive in Class V restorations after 18 months of clinical service . METHODS Thirty-three patients with non-carious cervical lesions were enrolled in the study . A total of 101 lesions were restored using one of the adhesives and a hybrid composite resin . Enamel was not beveled , nor was any mechanical retention placed . The restorations were evaluated at baseline , and at 6 and 18 months after placement using modified USPHS criteria . RESULTS Cumulative 18-month retention rates were 93.6 % for OptiBond Solo and 98.0 % for Prime & Bond 2.1 . The difference in retention rates was not statistically significant . For OptiBond Solo , the only notable problems were interfacial staining and marginal adaptation , both of which were less than ideal in 9 % of restorations . Marginal problems were slightly less frequent for Prime & Bond 2.1 restorations , but the difference was not significant . CONCLUSIONS Both adhesives provided Class V retention rates exceeding the 18-month , full acceptance guidelines set by the American Dental Association . Any additional benefit provided by the use of a filled adhesive was not detected in this 18-month clinical trial", "This study evaluated the effect of the elastic modulus and margin configuration on the clinical performance of resin-based composite restorations in Class V non-carious defects . One hundred and five cervical non-carious defects on buccal surfaces of canines and premolars were included in this study . Defects were r and omly divided into three Groups and restored according to the following techniques : Group 1 - -no enamel bevel was placed and the defect was restored with a microfilled resin-based composite ( Durafill VS ) ; Group 2 - -the enamel margin was beveled and the defect restored as in Group 1 ; Group 3-the enamel margin was beveled and the defect was restored with a flowable resin-based composite ( Natural Flow ) . Each group comprised 35 lesions . A total-etch , one-bottle adhesive ( One-Step ) was used in all groups . Retention rate , pre- and post-operative sensitivity , marginal discoloration and secondary caries were determined over a three-year period and the data were analyzed statistically . At six months post-insertion , the restorations placed with beveled enamel margins result ed in 100 % retention regardless of the composite used compared to a 66 % retention of the non-beveled margins . At two and three years , no significant difference in retention rate was found among the three groups . Post-operative sensitivity , marginal discoloration and secondary caries were not affected by enamel beveling and restorative material . Beveled enamel margins result ed in significantly better clinical retention in the first six months only . Enamel beveling and composite viscosity appeared to not significantly affect the clinical performance of Class V non-retentive composite restorations after three years", "PURPOSE The purpose of this in vitro study was to measure and compare the in vitro shear bond strengths ( SBS ) of the following dentin bonding systems to different dentin surfaces under simulated pulpal pressure : Liner Bond 2 ( self-etching ) ( LB2 ) , Liner Bond 2V ( self-etching ) ( LB2V ) , Opti Bond Solo ( single component ) ( OBS ) , Fuji Bond LC ( filled ) ( FBLC ) , Prime & Bond 2 - 1 ( single component ) ( P&B2 - 1 ) , and Solid Bond ( total etching ) ( SB ) . MATERIAL S AND METHODS Occlusal and buccal surfaces of 60 extracted human molars were prepared to expose the dentin bonding surface . After being wet ground with 600-grit abrasive papers , teeth were r and omly assigned to 6 equal groups of 10 each . The dentin surfaces were treated with the bonding systems mentioned above , and resin composite cylinders ( Clearfil AP-X ) were built up under simulated pulpal pressure when diluted bovine serum was used as the pulpal fluid . After one day of storage in 37 degrees C water , the specimens were shear tested to failure on an Instron machine . RESULTS The data were statistically analyzed with the Student 's t-test and a post hoc Tukey test . Comparing buccal surfaces , the post hoc Tukey test indicated no significant differences among all the test groups ( p > 0.05 ) . On occlusal surfaces , the post hoc Tukey test indicated significant differences among the tested groups ( p occlusal and buccal shear bond strength values in LB 2 , LB2V , and SB groups ( p strength of adhesion to dentin depends upon both the adhesive system used - with self-etching systems tending to show higher bond strengths than the other material s tested - and the location of the dentin , with significantly higher SBS being found on buccal surfaces in 3 of the 7 tested bonding systems", "Abstract The aim of this study was to compare the treatment results using four different types of tooth colored material s for restoring class V lesions . A total of 197 class V restorations ( n=197 ) were placed by one dentist in 37 patients on incisors , canines and premolars . The fillings were placed due to different indications : erosion/non-carious cervical defects ( n=69 ) , primary carious lesions ( n=57 ) , and for replacing defective existing fillings ( n=71 ) . The teeth were assigned on a r and om basis to four groups for restoration with either a composite ( group 1 : n=36 ; Tetric , Vivadent ) , or a polyacid-modified resin composite ( group 2 : n=79 ; Dyract , Dentsply ) , or one of two different resin-modified glass ionomer cements ( group 3 : n=51 , Fuji II LC , GC ; group 4 : n=31 , Photac-Fil , Espe ) . The restorations were evaluated by a single-blind design , according to a modified USPHS system 36 months following placement . Statistical analysis was completed with the Pearson Chi-square test for comparing the results of the four groups ( P survival rates were analyzed with the Kaplan-Meier estimator and the Log-rank test ( P shade match ( 86%/77%/58%/40 % ) , surface texture ( 81%/83%/16%/9 % ) , marginal integrity ( enamel ) ( 73%/67%/61%/61 % ) , marginal integrity ( dentin ) ( 86%/70%/55%/61 % ) , marginal discoloration ( enamel ) ( 59%/44%/58%/52 % ) , marginal discoloration ( dentin ) ( 82%/84%/71%/48 % ) , anatomic contours ( 91%/83%/39%/ 35 % ) . One Tetric restoration , five Dyract restorations , two Fuji II LC restorations and three Photac restorations were dislodged within the study period . The retention of the restorations showed no significant difference among the four material s. However , the clinical performance of the restorations retained over the 3-year period showed distinct differences for the four material s. The best clinical performance was observed for the resin composite , whereas the quality of the Dyract restorations without enamel etching was worse . The poorest results were obtained for the restorations with the resin-modified glass ionomers", "Compomers are defined as polyacid-modified resin composites . They are supposed to combine the advantages of traditional glass-ionomer cements with resin composites . This study clinical ly evaluated a compomer in cervical cavities . Sixty cervical cavities in premolars and molars ( 24 with cervical caries and 36 with abrasions ) r and omly divided into two groups of 30 teeth ( Group 1 and Group 2 ) were restored with Dyract ( DeTrey-Dentsply , York , PA 17405 - 0872 ) . The cavities of Group 2 were etched for 30 seconds with orthophosphoric acid before compomer application , while the Group 1 cavities received no treatment . All the restorations were evaluated every six months , up to 48 months : characteristics assessed according to USPHS-modified st and ards were retention , secondary caries , post-operative sensitivity , marginal adaptation and discoloration , color and wear . The Kaplan-Meier 's survival analysis was performed . In both groups , retention was high without any statistically significant difference . No difference was found between the two groups for caries , post-operative sensitivity and wear -- that all had a low incidence . Color was not perfectly matched , however , there was no statistically significant difference between the two groups . Marginal discoloration and marginal adaptation loss were significantly higher in non-etched group ( p failure required 17.2 % of restorations in the non-etched group and 10 % in the etched group to be replaced : this difference was not statistically significant . Dyract has an acceptable clinical behavior when used in cervical cavities . Its marginal adaptation is enhanced by etching", "The purpose of this double-blind clinical trial was to compare the retention rate in noncarious Class V lesions of two resin-based composite restorative material s with contrasting stiffness . Isolation with retraction cord , pressed paper triangles , and cotton rolls was used to closely mimic the procedures generally used in a practice setting . Thirty pairs of restorations were placed , one using Silux Plus and one using Z100 . The assignment of material was r and omized , and the subjects were unaware of the material used . All restorations were placed with a fourth-generation adhesive liner , Scotchbond Multi- Purpose . Evaluations were performed at baseline , 6 , 12 , 18 , and 24 months by two independent examiners using criteria developed by Cvar and Ryge in a forced consensus model . Examiners were unaware of the restoration 's group identity . No difference between the retention rates for the two groups was found after 24 months , bringing into question the role that a material 's stiffness plays in determining retention in a noncarious Class V lesion", "PURPOSE The aim of this double-blind r and omized study was to compare the clinical performance of a resin-modified glass ionomer ( Vitremer , 3 M ) and a polyacid-modified resin ( Dyract , Dentsply DeTrey ) in noncarious Class V restorations after 5 years . MATERIAL S AND METHODS Twelve patients , having at least one pair of equal-sized noncarious cervical lesions under occlusion and a mean age of 40 years ( range 19 to 63 years ; median 41 ) , were enrolled in this study . A total of 32 restorations ( 16 with each material ) were placed according to the manufacturers ' instructions by two calibrated operators . Two other independent examiners evaluated the restorations at baseline and after 5 years according to the USPHS criteria . The assessment criteria were : retention , anatomical form , marginal adaptation and marginal discoloration , color match , surface texture , and secondary caries . Statistical analysis was conducted using Fisher 's exact test ( alpha = 0.05 ) . RESULTS No secondary caries was detected with either material . The retention rate for Vitremer ( 93 % ) and for Dyract ( 78.5 % ) did not differ significantly ( p > 0.05 ) . Regarding anatomical form , only two restorations of each material were recorded as bravo . In terms of marginal adaptation , 38.5 % of Dyract restorations were rated alpha and 61.5 % bravo , while 84.6 % of Vitremer restorations were rated alpha and only 15.4 % bravo ( p marginal discoloration , 18.2 % of Dyract restorations and 84.6 % of Vitremer restorations were rated alpha , with the remaining rated bravo . 86 % of Vitremer restorations were rated as bravo and 23 % alpha for both surface texture and color match . All Dyract restorations were classified as alpha regarding surface texture , and only two Dyract restorations ( 18.2 % ) were classified as bravo in the color match item . CONCLUSION The marginal adaptation of the RMGIC ( Vitremer ) was significantly better , the marginal discoloration lower , and the retention rate higher ( though not significantly ) than that of the PMRC ( Dyract ) after 5 years in situ . Dyract performed better in terms of surface texture and color match in noncarious Class V restorations after 5 years", "OBJECTIVES The goal of this study was to illustrate and define the micromorphological spectrum which exists at the resin-dentin interface when two water-free , acetone-based , single-bottle primer/adhesive systems ( One-Step , Bisco , and Prime & Bond , Dentsply/L.D. Caulk ) were applied to acid-conditioned dentin under different dry and wet bonding conditions . METHODS Forty-eight 1 mm dentin discs were each conditioned with 10 % phosphoric acid and rinsed for 20 s. They were r and omly divided into 4 groups based upon the status of the remaining surface moisture ; Group I ( 30 s dry ) ; Group II ( 3 s dry ) ; Group III ( blot dry ) and Group IV ( overwet ) . Bonded dentin disc pairs were then demineralized in EDTA and embedded in epoxy resin for transmission electron microscopic examination . RESULTS The micromorphological spectra of the two bonding systems were essentially similar . Both were effected by even mild desiccation ( 3 s ) , result ing in incomplete intertubular resin infiltration . Optimal intertubular resin infiltration was achieved when the collagen network was kept moist and appeared relatively unaffected by the presence of excess surface moisture . On the other h and , intratubular resin infiltration was severely compromised in the presence of excess water within the dentinal tubules and at their openings in the dentin surface . The continuity of the resin layer deteriorated ; blister-like spaces formed on the dentin surface and resin globules were found around the tubular orifices and on the surface of the hybrid layer . In addition , a complex phase separation pattern was observed in Prime & Bond that was characterized by phase inversion in the presence of surface moisture . SIGNIFICANCE The \" window of opportunity \" for optimal interfacial integrity for both water-free systems appeared to depend upon keeping the demineralized collagen network moist , coupled with the complete evaporation of excess and \" displaced \" water from tissues prior to light-curing the prime/adhesives", "OBJECTIVES This study investigated the ultrastructure of the resin-dentine interface when a two-bottle primer system containing NTG-GMA ( N(p-tolyl)glycine-glycidyl methacrylate ) and BPDM ( biphenyl dimethacrylate ) was used with different concentrations of water as a part of the primer solvent : ( I ) an experimental version of All-Bond 2 with no water in primer A ; ( II ) a commercial version of All-Bond 2 ( Bisco , Itasca , IL , USA ) with 5 % water in primer A ; and ( III ) a former version of All-Bond 2 with 17 % water in primer A. METHODS Thirty-six 1-mm thick dentine discs prepared from third permanent molar teeth were each conditioned with 10 % phosphoric acid for 20 s and rinsed for 20 s. They were r and omly divided into three groups : Group A , conditioned dentine surface air-dried for 30 s ; Group B , air-dried for 3 s ; and Group C , blot-dried so that the dentine surface remained visibly moist . The three categories of primers were applied to each disc in 8 - 10 coats , result ing in nine sub-groups . Discs in each sub-group were bonded together to form disc-pairs using a chemical cure resin , demineralized in ethylene diamine tetraacetic acid ( EDTA ) and prepared for transmission electron microscopic examination . RESULTS With the use of the water-free primer version , sub-optimal hybridization was observed whenever dentine was dried prior to bonding ( Groups IA and IB ) . In the 5 % water version , prolonged desiccation result ed in compromised hybridization ( Group IIA ) , while resin globules were observed on the surface of the hybrid layer when a moist technique was employed ( Group IIC ) . In the 17 % water version , surface blisters and globules characteristic of the ' overwet phenomenon ' were observed in Groups IIIB and IIIC . CONCLUSION Between the two extremes of a morphological spectrum of bonding conditions , the different primer versions exhibited different sensitivity ranges . There was a shift in the ' window of opportunity ' for optimal hybridization and tubular seal depending on the water content of the primer system investigated", "PURPOSE To clinical ly evaluate the 3-year performance of a one-bottle dentin adhesive in the restoration of non-carious cervical lesions ( NCCLs ) with resin composite . MATERIAL S AND METHODS 105 NCCLs were restored with either AElite Flow , Bisco Glaze ( both flowable resin-based composites ) or Silux ( a microfilled resin-based composite ) , using One-Step dentin adhesive . The cavities were cleaned with pumice and water slurry , the dentin lightly roughened with a fine diamond bur , and the restorations placed according to the manufacturer 's instructions . Patients were recalled at 6 months , 1 year , 2 years and 3 years , and restoration integrity and marginal discoloration assessed . RESULTS The overall retention rates were : 6 months , 100 % ; 1 year , 95 % ; 2 years , 87 % ; 3 years , 75 % . Marginal discoloration was negligible , and there was no significant difference among the material s , although there was a trend for it to be greater around the Bisco Glaze restorations", "PURPOSE To evaluate dentin bond durability using current dentin adhesive resin bonding approaches over a 15-month period of water storage . MATERIAL S AND METHODS Forty-four extracted human molars were polished with 600-grit SiC papers exposing occlusal dentin , and r and omly distributed into four adhesive groups : total-etch 3-step ( TE3 ) ( Scotchbond Multi- Purpose , 3 M ESPE ) , total-etch 2-step ( TE2 ) ( Single Bond , 3 M ESPE ) , self-etch 2-step ( SE2 ) ( Clearfil SE Bond , Kuraray ) , and a self-etch 1-step ( SE1 ) ( Prompt L-Pop , 3 M ESPE ) . A resin composite crown was incrementally formed and light cured to approximately 6 mm in height . Microtensile specimens were fabricated and stored in distilled water containing 0.5 % chloramine T and tensile tested at 1 mm/min after 1 , 6 , and 15 months . The debond pathway was recorded as either involving the substrate or joint using scanning electron microscopy . SAS software was used to compute Weibull parameters and distributions , Log-rank and Wilcoxon tests were used for comparison of survival curves over time for each adhesive system and between adhesive systems . RESULTS The TE2 was significantly weaker than TE3 and SE2 after 1 and 6 months of storage , but all three systems were equivalent after 15 months of storage . The SE1 system could not be tested due to 58 of 65 specimens failing during specimen preparation . Failure modes were observed to be dependent upon adhesive system , with only the total-etch 2-step system demonstrating an increasing involvement in the adhesive joint over time . CONCLUSION Although differences in bond strength were observed across adhesive systems up to 6 months of storage , no differences were noted at 15 months . This may represent common degradative mechanisms", "While a one-year report had been previously published , this study was undertaken to evaluate the clinical performance and appearance of a resin-modified glass ionomer and a resin composite over two years . Thirty-seven pairs of restorations of FujI II LC and Z 250/Single Bond were placed in caries-free cervical erosion/abfraction lesions without tooth preparation . Restorations were clinical ly evaluated at baseline , 6 , 12 , 18 and 24 months using modified Ryge/USPHS criteria . No statistically significant difference ( p = 0.13 ) was observed in the overall performance of the material s. Retention was 96 % for the resin-modified glass ionomer and 81 % for the resin composite , with no additional restorations of either material lost after one year . As previously reported , retention of the Z 250 restorations at six months was below the minimum specified in the ADA Acceptance Program for Dentin and Enamel Adhesives . The resin composite restorations generally had a better appearance , with a 100 % alpha rating in color match , versus 85 % for the resin-modified glass ionomer", "PURPOSE To investigate the durability of three simplified systems in Class V non-carious abrasion/erosion lesions . METHODS 144 non-carious cervical dentin lesions were restored either with Clearfil Liner Bond 2 , a 2-step self-etching primer ( n = 46 ) , One Coat Bond , a one bottle total-etch system applied with one coat ( n = 46 ) , or Prompt-L-Pop , a 1-step self-etching primer ( \" all-in-one \" ) ( n = 52 ) , in 90 individuals . Ninety-eight of the lesions showed sclerotic dentin and 46 were non-sclerotic . Sixty-one were slightly roughened with a diamond bur before conditioning . The restorations were evaluated every 6 months during a 2-year period with slightly modified USPHS criteria . RESULTS All except three restorations were evaluated over 2 years . The cumulative loss rates for Clearfil Liner Bond 2 , One Coat Bond and Prompt-L-Pop were at 6 months : 4.3 , 2.2 and 3.9 % , at 18 months : 4.3 , 10.9 and 15.4 % and at 24 months : 8.7 , 13.0 and 21.2 % , respectively . The cumulative loss rates of the material s in sclerotic lesions ( 15.7 % ) versus non-sclerotic lesions ( 14.0 % ) were not significanty different . Restorations placed with a diamond bur-roughened lesions showed a loss rate of 14.5 % , while for the non-roughened lesions the frequency was 14.8 %" ]	411891e0-06ff-11f0-808a-c43d1ab1c353
Graphical abstract Figure . No Caption available . Abstract The results of human clinical trials have revealed that the effects of resveratrol on adipokines are inconsistent . Our objective was to eluci date the role of resveratrol supplementation on adipokines through a systematic review and a meta‐ analysis of available r and omized placebo‐controlled trials ( RCTs ) .1 The search included PubMed ‐ MEDLINE , SCOPUS and ISI web of sciences data base till up to 6th November 2016 . Weight mean differences (WMD)2 were calculated for net changes in adipokines using fixed‐effects or r and om‐effects models ; meta‐regression analysis and publication bias were conducted in accordance with st and ard methods . Nine RCTs with 11 treatment arms were eligible for inclusion in this systematic review and meta‐ analysis . Meta‐ analysis of data from 10 treatment arms showed a significant change in plasma adiponectin concentrations following resveratrol supplementation ( WMD : 1.10 & mgr;g/ml , 95%CI : 0.88 , 1.33 , p greater adiponectin‐reducing effect in trials with higher than or equal to 100 mg/day ( WMD : 1.11 & mgr;g/ml , 95%CI : 0.88 , 1.34 , p change in plasma leptin concentrations following resveratrol supplementation ( WMD : 3.77 ng/ml , 95 % CI : −2.28 , 9.83 , p = 0.222 ; Q = 8.00 , I2 = 50.01 % ) . Resveratrol significantly improves adiponectin but does not affect leptin concentrations . Additional studies are required to further evaluate the potential benefits of resveratrol on adipokines in humans	[ "BACKGROUND Green tea consumption has been associated with favorable changes in body weight and obesity-related hormones , although it is not known whether these changes result from green tea polyphenols or caffeine . OBJECTIVE We examined the impact of decaffeinated green tea extract ( GTE ) containing 843 mg of (-)-epigallocatechin-3-gallate on anthropometric variables , obesity-associated hormones , and glucose homeostasis . METHODS The Minnesota Green Tea Trial was a 12-mo r and omized , double-blind , placebo-controlled clinical trial of 937 healthy postmenopausal women assigned to either decaffeinated GTE ( 1315 mg total catechins/d ) or a placebo , stratified by catechol-O-methyltransferase ( COMT ) genotype . This study was conducted in a subset of 237 overweight and obese participants [ body mass index ( BMI ) ≥25 kg/m(2 ) ] . RESULTS No changes in energy intake , body weight , BMI , or waist circumference ( WC ) were observed over 12 mo in women taking GTE ( n = 117 ) or placebo ( n = 120 ) . No differences were seen in circulating leptin , ghrelin , adiponectin , or glucose concentrations at month 12 . Participants r and omly assigned to GTE with baseline insulin ≥10 μIU/mL ( n = 23 ) had a decrease in fasting serum insulin from baseline to month 12 ( -1.43 ± 0.59 μIU/mL ) , whereas those r and omly assigned to placebo with baseline insulin ≥10 μIU/mL ( n = 19 ) had an increase in insulin over 12 mo ( 0.55 ± 0.64 μIU/mL , P significantly lower adiponectin ( 5.97 ± 0.50 compared with 7.58 ± 0.53 μg/mL , P = 0.03 ) and greater insulin concentrations ( 7.63 ± 0.53 compared with 6.18 ± 0.36 μIU/mL , P = 0.02 ) at month 12 compared with those with the low-activity ( A/A ) genotype , regardless of treatment group . CONCLUSIONS Decaffeinated GTE was not associated with reductions in body weight , BMI , or WC and did not alter energy intake or mean hormone concentrations in healthy postmenopausal women over 12 mo . GTE decreased fasting insulin concentrations in those with elevated baseline fasting concentrations . The high-activity form of the COMT enzyme may be associated with elevations in insulin and a reduction in adiponectin concentrations over time . This trial was registered at http://www . clinical trials.gov as NCT00917735", "The polyphenol resveratrol is considered to exert many beneficial actions , such as antioxidant , anti-inflammatory , insulin-sensitizer and anticancer effects . Its benefits in patients with type 2 diabetes mellitus ( T2DM ) are controversial . Our aims were to determine whether resveratrol supplementation at two different dosages ( 500 and 40mg/day ) for 6 months i ) reduced the concentrations of C-reactive-protein ( CRP ) and ii ) ameliorated the metabolic pattern of T2DM patients . In the present double-blind , r and omized , placebo-controlled trial , 192 T2DM patients were r and omized to receive resveratrol 500mg/day ( Resv500arm ) , resveratrol 40mg/day ( Resv40arm ) or placebo for 6-months . At baseline and at the trial end , CRP values , anthropometric , metabolic and liver parameters were determined . No serious adverse event occurred . A dose-dependent , though not significant , CRP decrease of 5.6 % ( Resv40arm ) and 15.9 % ( Resv500arm ) was observed vs placebo . We failed to detect significant differences in weight , BMI , waist circumference , and values of arterial blood pressure , fasting glucose , glycated hemoglobin , insulin , C-peptide , free fatty acids , liver transaminases , uric acid , adiponectin , interleukin-6 , in both the Resv500 and Resv40 arms vs placebo . Total cholesterol and triglycerides slightly increased in the Resv500arm . Subgroup analyses revealed that lower diabetes duration ( in both Resv500 and Resv40arms ) , and , in the Resv500arm , younger age , aspirin use and being a smoker were associated with a significantly higher CRP reduction vs placebo . The supplementations with 40mg/day or 500mg/day resveratrol did neither reduce CRP concentrations , nor improve the metabolic pattern of T2DM patients", "OBJECTIVE The plasma leptin/adiponectin ( L/A ) ratio has been proposed as a preferential marker of atherosclerosis susceptibility compared to leptin and adiponectin alone . We determined the extent to which the L/A ratio predicts incident cardiovascular disease ( CVD ) taking account of clinical risk factors , microalbuminuria , the total cholesterol/HDL cholesterol ( TC/HDL-C ratio ) , triglycerides , high sensitive C-reactive protein ( hs-CRP ) and insulin sensitivity ( homeostasis model assessment ( HOMA(ir ) ) ) . METHODS A community-based prospect i ve nested case-control study was carried out in 103 non-diabetic men who developed a first cardiovascular event ( cases ) and 106 male control subjects ( no clinical ly manifest CVD and no lipid lowering drug use at baseline ; median follow-up of 3.0 and 10.5 years , respectively ) . Plasma leptin , adiponectin , the leptin/adipnectin ( L/A ) ratio , as well as hs-CRP , HOMA(ir ) and the TC/HDL-C ratio were determined at baseline . RESULTS Plasma leptin levels and the L/A ratio were higher in cases vs. controls ( p=0.002 for both ) , but the difference in adiponectin was not significant ( p=0.10 ) . Age-adjusted incident CVD was associated with plasma leptin , adiponectin and the L/A ratio ( p=0.045 to p=0.001 ) . The relationships of incident CVD with plasma leptin ( p=0.19 ) and adiponectin ( p=0.073 ) lost statistical significance after additional adjustment for smoking , waist circumference , hypertension , microalbuminuria , the TC/HDL-C ratio , hs-CRP and HOMA(ir ) . In this fully adjusted analysis , the L/A ratio remained predictive of incident CVD ( hazard ratio : 1.40 ( 95 % CI 1.05 - 1.87 ) , p=0.024 ) . CONCLUSION This study suggests that the L/A ratio may be a preferential marker of a first cardiovascular event in men compared to plasma leptin and adiponectin levels alone", "CONTEXT Adiponectin , a recently discovered adipocyte-derived peptide , is involved in the regulation of insulin sensitivity and lipid oxidation and , purportedly , in the development of atherosclerosis and coronary heart disease in humans . OBJECTIVE To assess prospect ively whether plasma adiponectin concentrations are associated with risk of myocardial infa rct ion ( MI ) . DESIGN , SETTING , AND PARTICIPANTS Nested case-control study among 18 225 male participants of the Health Professionals Follow-up Study aged 40 to 75 years who were free of diagnosed cardiovascular disease at the time of blood draw ( 1993 - 1995 ) . During 6 years of follow-up through January 31 , 2000 , 266 men subsequently developed nonfatal MI or fatal coronary heart disease . Using risk set sampling , controls were selected in a 2:1 ratio matched for age , date of blood draw , and smoking status ( n = 532 ) . MAIN OUTCOME MEASURE Incidence of nonfatal MI and fatal coronary heart disease by adiponectin level . RESULTS After adjustment for matched variables , participants in the highest compared with the lowest quintile of adiponectin levels had a significantly decreased risk of MI ( relative risk [ RR ] , 0.39 ; 95 % confidence interval [ CI ] , 0.23 - 0.64 ; P for trend hemoglobin A1c or C-reactive protein levels also had little impact , but additional adjustment for low- and high-density lipoprotein cholesterol levels modestly attenuated this association ( RR , 0.56 ; 95 % CI , 0.32 - 0.99 ; P for trend = .02 ) . CONCLUSIONS High plasma adiponectin concentrations are associated with lower risk of MI in men . This relationship can be only partly explained by differences in blood lipids and is independent of inflammation and glycemic status", "The search for complementary treatments in primary prevention of cardiovascular disease ( CVD ) is a high-priority challenge . Grape and wine polyphenol resveratrol confers CV benefits , in part by exerting anti-inflammatory effects . However , the evidence in human long-term clinical trials has yet to be established . We aim ed to investigate the effects of a dietary resveratrol-rich grape supplement on the inflammatory and fibrinolytic status of subjects at high risk of CVD and treated according to current guidelines for primary prevention of CVD . Seventy-five patients undergoing primary prevention of CVD participated in this triple-blinded , r and omized , parallel , dose-response , placebo-controlled , 1-year follow-up trial . Patients , allocated in 3 groups , consumed placebo ( maltodextrin ) , a resveratrol-rich grape supplement ( resveratrol 8 mg ) , or a conventional grape supplement lacking resveratrol , for the first 6 months and a double dose for the next 6 months . In contrast to placebo and conventional grape supplement , the resveratrol-rich grape supplement significantly decreased high-sensitivity C-reactive protein ( -26 % , p = 0.03 ) , tumor necrosis factor-α ( -19.8 % , p = 0.01 ) , plasminogen activator inhibitor type 1 ( -16.8 % , p = 0.03 ) , and interleukin-6/interleukin-10 ratio ( -24 % , p = 0.04 ) and increased anti-inflammatory interleukin-10 ( 19.8 % , p = 0.00 ) . Adiponectin ( 6.5 % , p = 0.07 ) and soluble intercellular adhesion molecule-1 ( -5.7 % , p = 0.06 ) tended to increase and decrease , respectively . No adverse effects were observed in any patient . In conclusion , 1-year consumption of a resveratrol-rich grape supplement improved the inflammatory and fibrinolytic status in patients who were on statins for primary prevention of CVD and at high CVD risk ( i.e. , with diabetes or hypercholesterolemia plus ≥1 other CV risk factor ) . Our results show for the first time that a dietary intervention with grape resveratrol could complement the gold st and ard therapy in the primary prevention of CVD", "We examined the effects of quercetin-rich onion peel extract supplementation on adipokine expressions from adipose tissues in a diet-induced obese animal model . Male Sprague-Dawley rats ( n = 24 ) were r and omly assigned into control ( n = 8) , high fat diet ( HF , n = 8) and high fat diet with onion peel extract ( HFOE , n = 8) . After 8 weeks , serum biochemical parameters , weights of adipose tissues ( epididymal , perirenal and mesenteric fats ) and adipokine mRNA levels ( adiponectin , IL (interleukin)-6 and visfatin ) along with PPAR ( peroxisome proliferator-activated receptor ) γ2 from adipose tissues were measured . After the 8 week supplementation , mesenteric fat weights were lower in the HFOE group than the HF group ( p ) . Adiponectin mRNA levels ( mesenteric fats ) were remarkably higher in the HFOE group than the other groups ( p . Levels of PPARγ2 mRNA ( mesenteric fats ) were significantly higher in the HF group ( p The IL-6 mRNA levels ( perirenal and mesenteric fats ) were higher in the HF and HFOE groups , but those in the HFOE group were slightly lower than those in the HF group . In conclusion , quercetin-rich onion peel extract supplementation influenced adipokine expressions , particularly from mesenteric fat , addressing the modulatory effect of this substance on obesity-induced inflammation", "OBJECTIVE To evaluate the efficacy of an orlistat-resveratrol ( O-R ) combination in subjects with obesity over a 6-month period . METHODS This study was a double-blind , parallel , r and omized controlled clinical trial . Patients fulfilling the selection criteria ( age from 20 to 60 years and body mass index ( BMI ) ≥30 and ≤39.9 kg/m(2 ) ) consumed an energy-reduced diet with 500 fewer calories than their usual diet for 2 weeks . Then the participants were r and omly assigned to four groups , placebo , resveratrol , orlistat , or O-R , and they consumed the energy-reduced diet for 6 months . The study consisted of seven visits . During each visit , a 24-h recall was performed , along with measurements of anthropometric and serum biochemical parameters . RESULTS A total of 161 participants were selected . Of these , 84 participants completed the study . A significant weight loss of -6.82 kg ( 95 % CI -8.37 to -5.26 ) was observed in the O-R group compared with -3.50 kg ( -5.05 to -1.95 , P = 0.021 ) in the placebo group . In contrast , the -6.02 kg ( -7.68 to -4.36 ) orlistat and -4.68 kg ( -6.64 to -2.71 ) resveratrol monotherapy losses did not significantly differ from the placebo . Significant decreases in BMI , waist circumference , fat mass , triglycerides , leptin , and leptin/adiponectin ratio were observed with the O-R combination . CONCLUSIONS The O-R combination was the most effective weight loss treatment", "Numerous studies have shown that resveratrol ( RES ) exerts anti-inflammatory effects but human trials evidencing these effects in vivo are limited . Furthermore , the molecular mechanisms triggered in humans following the oral intake of RES are not yet understood . Therefore , the purpose of this study was to investigate the molecular changes in peripheral blood mononuclear cells ( P BMC s ) associated to the one-year daily intake of a RES enriched ( 8 mg ) grape extract ( GE-RES ) in hypertensive male patients with type 2 diabetes mellitus ( T2DM ) . We used microarrays and RT-PCR to analyze expression changes in genes and microRNAs ( miRs ) involved in the inflammatory response modulated by the consumption of GE-RES in comparison to a placebo and GE lacking RES . We also examined the changes in several serobiochemical variables , inflammatory and fibrinolytic markers . Our results showed that supplementation with GE or GE-RES did not affect body weight , blood pressure , glucose , HbA1c or lipids , beyond the values regulated by gold st and ard medication in these patients . We did not find either any significant change on serum inflammatory markers except for a significant reduction of ALP and IL-6 levels . The expression of the pro-inflammatory cytokines CCL3 , IL-1β and TNF-α was significantly reduced and that of the transcriptional repressor LRRFIP-1 increased in P BMC s from patients taking the GE-RES extract . Also , a group of miRs involved in the regulation of the inflammatory response : miR-21 , miR-181b , miR-663 , miR-30c2 , miR-155 and miR-34a were found to be highly correlated and altered in the group consuming the GE-RES for 12 months . Our results provide preliminary evidence that long-term supplementation with a grape extract containing RES downregulates the expression of key pro-inflammatory cytokines with the involvement of inflammation-related miRs in circulating immune cells of T2DM hypertensive medicated patients and support a beneficial immunomodulatory effect in these patients" ]	4118921c-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Mini-incision total hip replacement continues the current trend in orthopaedics and other specialties toward smaller-incision surgery . The purpose of this systematic review was to assess the effectiveness and safety of single mini-incision compared with st and ard-incision total hip replacement for treatment of arthritis of the hip . METHODS We conducted an electronic literature search for relevant studies published in any language up to March 2010 . Key conference proceedings and national orthopaedic registries were search ed , professional organizations and implant manufacturers were approached , and reference lists from included studies were screened . We included r and omized and quasi-r and omized controlled trials assessing single mini-incision surgery , defined as an incision of ≤ 10 cm , compared with st and ard primary total hip replacement . Two review ers independently assessed studies for inclusion and extracted data . RESULTS Fifteen r and omized and five quasi-r and omized controlled trials , involving 1857 participants , were eligible . Included trials were of mixed method ological quality , with the sample size ranging from twenty to 219 . Mean follow-up periods were short , ranging from six weeks to three years . Compared with st and ard total hip replacement , mini-incision procedures may have small perioperative advantages in terms of less blood loss , shorter operative time , and shorter inpatient stay , but the differences were not clinical ly important . Few complications were reported , and the complication rate did not differ significantly between groups . There was insufficient evidence to suggest any major difference in the short-term revision rate , and confidence intervals for surrogate measures for long-term outcome were broad enough to include clinical ly important differences in favor of either approach . CONCLUSIONS Although there were marginal short-term advantages and disadvantages for each of the surgical techniques , there was no strong evidence either for or against mini-incision compared with st and ard-incision total hip replacement . Importantly , evidence on longer-term performance , especially the risk of revision arthroplasty , for mini-incision hip arthroplasty is very limited	[ "Implant malposition and poor fixation are potential risks of compromising long-term results after total hip arthroplasty performed with a minimally invasive technique . Between September 2000 and February 2002 , 120 cemented primary total hip arthroplasties were performed at the authors ' institutions in patients with primary osteoarthritis of the hip and with BMI lower than 35 . In 60 of these cases selected at r and om , a posterolateral incision no longer than 10 cm was used . The other 60 THA 's were performed through a st and ard posterolateral approach . The inclination and anteversion of the cup and the position of the femoral stem were assessed on radiographs and statistically evaluated . In the miniinvasive group , the average inclination angle of the cup was 42.3 degrees ( range : 36 to 52 degrees ) and the anteversion angle 13.6 degrees ( range : 6 to 29 degrees ) . The coronal alignment of the femoral component was within 3 degrees of neutral in 54 cases ( 90.0 % ) . Following conventional implantation in the other group , the average cup inclination angle was 42.4 degrees ( range : 35 to 50 degrees ) and the anteversion angle 13.6 degrees ( range : 8 to 24 degrees . A total of 53 stems ( 88.3 % ) were implanted optimally . Statistical analysis found no significant difference between the two groups regarding components position . These findings suggest that using a smaller posterolateral incision as was done in this study does not introduce a potential risk of compromising long-term results", "BACKGROUND AIMS Evaluation of : 1 . early clinical and radiographic results of total hip arthroplasty ( THA ) through a st and ard lateral direct approach , 2 . early clinical and radiographic results of THA through a minimal lateral approach , 3 . comparison of the results of THA in these two groups . MATERIAL AND METHODS 120 THAs ( 60 cementless and 60 cemented ) done in 120 patients due to degenerative changes were evaluated prospect ively . 60 THAs were done through a minimal lateral approach and constituted a study group . 60 THAs were done through a direct lateral approach and constituted a control group . The mean age of the 120 patients ( 98 women and 22 men ) was 45 y.o . ( range : 32 - 67 y.o . ) . The duration of follow-up in the study group was from 6 to 12 months ( mean : 8.5 months ) . The duration of follow-up in the control group was from 10 to 16 months ( mean : 10.5 months ) . Mean preoperative functional status of the study group was 44.5 points according to the Harris hip score . Radiographic evaluation of the results was done according to the criteria of the Joint Committee of the Hip Society , AAOS and SICOT . RESULTS 6 months after THA , clinical results were 92 pts in the study group and 88 pts in the control group . Radiographic outcomes were very good in all 120 patients from both arms : there were no differences between the control and study group . The incidence of complications was similar in both groups . CONCLUSIONS Minimally invasive THA demonstrated its value in the treatment of degenerative changes of the hip joint with regard to short-term outcomes . The clinical and radiographic outcomes were comparable between the st and ard and minimally invasive approaches . Success with THA using a minimally invasive approach depends on excellent operative technique and experience with st and ard hip approaches rather than on the use of special instruments", "BACKGROUND Minimally invasive total hip arthroplasty has stirred substantial controversy with regard to whether it provides superior outcomes compared with total hip arthroplasty performed through longer incisions . The orthopaedic literature is deficient in well- design ed scientific studies to support the clinical superiority of this approach . The objective of this study was to compare the results of a single mini-incision approach with those of a st and ard-incision total hip arthroplasty in the early postoperative period . METHODS Two hundred and nineteen patients ( 219 hips ) admitted for unilateral total hip arthroplasty between December 2003 and June 2004 were r and omized to undergo surgery through a short incision of All patients were blinded to the size of the incision for the duration of the hospital stay . The anesthetic , analgesic , and postoperative physiotherapy protocol s were st and ardized , with the staff also blinded to the technique used . A single surgeon , who had performed more than 300 short-incision hip replacements prior to the start of this study and who performs an average of 415 primary total hip replacements a year , performed all procedures through a single-incision posterior approach using a cementless cup and cemented stem . RESULTS The two groups were matched for age , grade according to the system of the American Society of Anesthesiologists , and body mass index . No significant difference was detected with respect to postoperative hematocrit , blood transfusion requirements , pain scores , or analgesic use . We found no difference in early walking ability or length of hospital stay and no difference in component placement , cement-mantle quality , or functional outcome scores at six weeks . The patient variables significantly associated with a probability of early discharge independent of incision length were patient age and preoperative hemoglobin levels ( p surgical scars contracted significantly over six weeks ( p single-incision posterior approach by a high-volume hip surgeon with extensive experience in less invasive approaches to the hip is safe and reproducible . However , it offers no significant benefit in the early postoperative period compared with a st and ard incision of 16 cm . As it is not known whether lower-volume and less-experienced surgeons can achieve similar results , the mini-incision technique merits further study before wide dissemination and implementation of this family of surgical approaches can be recommended", "OBJECTIVE To report the clinical outcome of minimally invasive total hip arthroplasty with anterior incision . METHODS One hundred and twenty cases were r and omly divided into two groups . Sixty cases ( group 1 ) who had undergone a mini-invasive THA were compared with 60 cases ( group 2 ) who had undergone THA with st and ard posterolateral incision . The operation time , length of incision , blood loss , anteversion angle of acetabulum cup , Harris score and complications were observed . RESULT The average operation time was almost the same ; The average length of incision for group 1 was 7.9 cm ( 7.4 - 9.0 cm ) and 16.3 cm ( 14 - 22 cm ) for group 2 ( P average blood loss for group 1 was 350 ml ( 250 - 530 ml ) and 650 ml ( 400 - 1200 ml ) for group 2 , there was significant difference between two groups ( P mean anteversion angles of cup were 24 degrees ( 19 degrees - 27 degrees ) for group 1 and 19 degrees ( 15 degrees - 22 degrees ) for group 2 . The average length of post-operative hospital stay was 7 days ( 5 - 8 days ) in group 1 and 13.5 days ( 12 - 16 days ) in group 2 ( P Harris score of group 1 was 91.4 ( 67 - 94 ) and 78.5 ( 67 - 91 ) for group 2 at the 3 month follow-up ( P 0.05 ) , but the average ROM of group 1 were definitely more greater than that of group 2 ( 110.0 degrees + /- 3.2 degrees vs. 90.0 degrees + /- 2.9 degrees P cup reinsertion in group 1 because of large anteversion angle ; 2 cases of symptomatic DVT and 1 case of lethargy because of cerebral infa rct ion happened in group 2 . CONCLUSIONS Minimally invasive total hip arthroplasty using anterior approach is a safe and effective technique with the advantages of less soft tissue damage and less blood loss", "Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists", "BACKGROUND Minimally invasive total hip arthroplasty is purported to allow an improved and faster rehabilitation in the immediate postoperative period because of reduced soft-tissue damage compared with total hip arthroplasty performed with use of a st and ard approach . In the present study , a minimally invasive approach was compared with a traditional st and ard approach in terms of the effect on gait kinematics as demonstrated with gait analysis and electromyography . METHODS Twenty r and omized patients who underwent a primary total hip replacement with use of a minimally invasive modified Watson-Jones approach ( minimally invasive group ) were compared with a group of twenty patients who underwent a total hip arthroplasty with use of a st and ard transgluteal Hardinge approach ( st and ard group ) . All patients received the same cementless implant , inserted with use of st and ard instruments , and all operations were performed by a single , experienced surgeon . The patients were evaluated with use of three-dimensional gait analysis and dynamic electromyograms at three time points : preoperatively , ten days postoperatively , and twelve weeks postoperatively . Temporospatial and joint-kinematic parameters were evaluated . RESULTS There were no significant differences between the two groups with regard to the temporospatial variables of velocity , cadence , step length , and stride length at any tested time point . With regard to the range of motion of the operatively treated hip , the minimally invasive group had a smaller decrease at the ten-day time point in comparison with the st and ard group . However , this finding was not significant . The reduction in the range of motion was mainly caused by reduced hip extension . A compensatory increase in the pelvic tilt was observed in both groups . One patient in the st and ard group showed a positive Trendelenburg gait ten days postoperatively ; it had disappeared completely at the twelve-week time point . CONCLUSIONS With regard to gait kinematics in the early postoperative period ( three months ) , the present study showed no significant benefit for patients who underwent a total hip arthroplasty through a minimally invasive Watson-Jones approach in comparison with those who were managed with a st and ard transgluteal approach", "Minimally invasive surgery has become a trend over the last few years in all aspects of orthopaedic surgery , including total hip arthroplasty . So-called mini-incision techniques involve limiting the length of the skin incision to 10 cm with use of either an anterior , lateral or posterior approach . Between March 2004 and December 2005 one hundred consecutive unilateral total hip replacements were performed by the same senior surgeon in our institute . All patients were r and omly assigned to study group ( group A ) or control group ( group B ) . In group A ( 50 patients ) the skin incision was 8 cm ; in group B ( 50 patients ) the skin incision was st and ard ( about 12 - 14 cm ) . Patient demographic data , including sex , age , height , weight , BMI , diagnosis and preoperative Harris hip score were recorded . Other criteria evaluated included the perioperative and postoperative complications , the surgical time , the blood loss , the length of the incision , the acetabular and stem positions , the length of hospital stay , Harris Hip Score ( HHS ) and the WOMAC osteoarthritis index at six months . No significant differences were found between the groups with respect to the average surgical time , the acetabular and stem position , the length of hospital stay and the Harris Hip Score ( HHS ) and the WOMAC osteoarthritis index at six months . A significant lower blood loss was found in the mini-incision group . A higher percentage of peri-operative complications was recorded in Group A ( two stupor of sciatic nerve and one fracture of the greater trochanter ) . On the basis of our experience we could speculate that minimally invasive surgery should be directed to the new surgical approach with muscle sparing , instead of a shorter skin incision using st and ard approaches", "The purpose of this prospect i ve r and omized study was to compare the early results of primary total hip arthroplasties performed with a minimally invasive technique or a st and ard technique . A consecutive series of 70 patients who underwent primary bilateral simultaneous total hip arthroplasties was studied . All procedures were performed through a posterolateral approach . Operative times and duration of hemovac drains were significantly shorter in the group with a minimally invasive technique ( P risk of infection when using this technique . There were no any late transfusions in any of our patients postdischarge . This minimally invasive technique did not offer any advantages because the results were not different , and in our h and s , it increased our infection rate", "Patients without prior hip surgery and body mass index lower than 30 undergoing primary total hip arthroplasty were eligible to participate in a r and omized prospect i ve study comparing a minimally invasive with a st and ard approach . The patients were r and omized to receive incisions of 8 cm ( group A , n = 28 ) or 15 cm ( group B , n = 32 ) . The groups were similar demographically . Patients in group A had significantly less intraoperative blood loss ( P total blood loss ( P Operative time , transfusion requirements , narcotic usage , length of hospital stay , achievement of rehabilitation milestones , cane usage , and complications were similar in both groups . There was no difference between the groups at 1- and 2-year follow-up . Compared with a st and ard incision , patients who underwent a minimally invasive total hip arthroplasty demonstrated decreased blood loss and limped less at 6-week follow-up", "BACKGROUND The benefits of minimally invasive total hip arthroplasty continue to be debated . The objective of this study was to investigate the role of patient education , accelerated rehabilitation , and improved pain control on the outcome of total hip arthroplasty performed through a small incision . METHODS One hundred patients undergoing total hip arthroplasty at our institution were r and omized into one of four groups on the basis of the size of the incision , preoperative counseling , the type of preoperative and postoperative rehabilitation , and the analgesia protocol . The operative parameters , complications , time to discharge to home , functional improvement , and patient satisfaction were assessed . RESULTS The demographic distribution among the four groups was similar . The extent of functional improvement at the time of discharge to home , patient satisfaction , and walking ability at the time of discharge were better in patients who had received an accelerated preoperative and postoperative rehabilitation regimen regardless of the size of the incision . There was no difference in estimated blood loss , mean operative time , transfusion needs , or complications among the groups . CONCLUSIONS This study highlights the importance of factors such as family education , patient preconditioning , preemptive analgesia , and accelerated preoperative and postoperative rehabilitation in influencing the outcome of total hip arthroplasty . The aforementioned factors , and not the surgical technique per se , may play a major role in imparting the better outcome after minimally invasive total hip arthroplasty that has been reported by various investigators", "BACKGROUND The aim of this prospect i ve r and omized study was to compare the results after total hip replacement ( THR ) using an MIS approach versus a regular transgluteal approach ( Bauer approach ) . METHOD We compared 20 THRs using a modified Watson-Jones minimally invasive approach ( MIS group ) with 20 conventionally performed THRs using a Bauer approach ( control group ) . In all cases , the same implants ( Trilogy cup , MAYO stem ) were used . The Harris Hip Score ( HHS ) , the visual analogue scale , myoglobin level , and creatinine kinase level were measured preoperatively and up to 3 months postoperatively . RESULTS Advantages of the MIS group were evaluated using the HHS in the categories of activity and range of motion 6 weeks postoperatively . In terms of function , gait , and total HHS , we found benefits in the MIS group 6 and 12 weeks postoperatively . Up to 48 h postoperatively , patients in the MIS group had lower myoglobin blood levels . No differences were found in creatinine kinase levels , pain sensation as measured by visual analogue scale , or implant positioning . CONCLUSION Use of the minimally invasive Watson-Jones approach shows advantages compared with the transgluteal Bauer approach 6 and 12 weeks postoperatively . Up to now there has been no prospect i ve r and omized clinical study that has definitely shown the superiority of the minimally invasive procedure . For that reason , the conventional approaches in THR are still the gold st and ard", " Twenty patients who underwent total hip arthroplasty were r and omly allocated to have surgery through a mini incision of or = 8 cm ( mini-incision surgery [ MIS ] group , n = 10 ) or a st and ard incision of 14 cm ( st and ard group , n = 10 ) . A laser Doppler flowmeter was used to measure the intraoperative blood flow of the skin . The measurements were performed at 2 regions , specifically , anterior and posterior regions across the middle points of skin incision . The measurements were taken before making the incision and after implantation . As a control , the skin blood flow over the anterior superior iliac spine was measured . After implantation , mean skin blood flows at both regions in the MIS group were significantly decreased by 32 % and 33 % . However , the corresponding flows in st and ard group and control regions were constant during operation" ]	41189258-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Poor lifestyle behaviors , including suboptimal diet , physical inactivity , and tobacco use , are leading causes of preventable diseases globally . Although even modest population shifts in risk substantially alter health outcomes , the optimal population -level approaches to improve lifestyle are not well established . METHODS AND RESULTS For this American Heart Association scientific statement , the writing group systematic ally review ed and grade d the current scientific evidence for effective population approaches to improve dietary habits , increase physical activity , and reduce tobacco use . Strategies were considered in 6 broad domains : ( 1 ) Media and educational campaigns ; ( 2 ) labeling and consumer information ; ( 3 ) taxation , subsidies , and other economic incentives ; ( 4 ) school and workplace approaches ; ( 5 ) local environmental changes ; and ( 6 ) direct restrictions and m and ates . The writing group also review ed the potential contributions of healthcare systems and surveillance systems to behavior change efforts . Several specific population interventions that achieved a Class I or IIa recommendation with grade A or B evidence were identified , providing a set of specific evidence -based strategies that deserve close attention and prioritization for wider implementation . Effective interventions included specific approaches in all 6 domains evaluated for improving diet , increasing activity , and reducing tobacco use . The writing group also identified several specific interventions in each of these domains for which current evidence was less robust , as well as other inconsistencies and evidence gaps , informing the need for further rigorous and interdisciplinary approaches to evaluate population programs and policies . CONCLUSIONS This systematic review identified and grade d the evidence for a range of population -based strategies to promote lifestyle change . The findings provide a framework for policy makers , advocacy groups , research ers , clinicians , communities , and other stakeholders to underst and and implement the most effective approaches . New strategic initiatives and partnerships are needed to translate this evidence into action	[ "OBJECTIVES To investigate the association between distance to the closest supermarket and a composite measure of diet , the diet quality index for pregnancy ( DQI-P ) was constructed . METHODS Data from the Pregnancy , Infection and Nutrition ( PIN ) cohort , a prospect i ve study of determinants of preterm birth , were analyzed . Food frequency question naires were used to construct DQI-P which includes : servings of grains , vegetables , fruits , folate , iron and calcium intake , percentage of calories from fat , and meal pattern score . Street address of residence , supermarkets , grocery and convenience stores were geocoded . Participants with complete food frequency and address data were included ( n = 918 ) . Multinomial logistic regression was used to estimate the conditional association of food outlets on diet quality , controlling for confounders and using a robust variance estimator to account for clustering of neighborhood characteristics . RESULTS Women living greater than 4 miles from a supermarket were more than twice the odds ( adjusted odds ratio = 2.16 ; 95 % confidence interval = 1.2 , 4.0 ) of falling into the lowest compared to highest DQI-P tertile compared to women living within 2 miles of a supermarket , after controlling for individual characteristics , other food retail outlets . CONCLUSION These findings suggest that proximity of food retail outlets influences the diet quality of pregnant women", "OBJECTIVE To evaluate the effectiveness of a worksite health promotion program on improving cardiovascular disease risk factors . METHODS In St Louis , Missouri from 2005 to 2006 , 151 employees ( 134 F , 17 M , 81 % overweight/obese ) participated in a cohort-r and omized trial comparing assessment s + intervention ( worksite A ) with assessment s only ( worksite B ) for 1 year . All participants received personal health reports containing their assessment results . The intervention was design ed to promote physical activity and favorable dietary patterns using pedometers , healthy snack cart , WeightWatchers(R ) meetings , group exercise classes , seminars , team competitions , and participation rewards . Outcomes included BMI , body composition , blood pressure , fitness , lipids , and Framingham 10-year coronary heart disease risk . RESULTS 123 participants , aged 45+/-9 yr , with BMI 32.9+/-8.8 kg/m(2 ) completed 1 year . Improvements ( P fitness , blood pressure , and total- , HDL- , and LDL-cholesterol . Additional improvements occurred at worksite A in BMI , fat mass , Framingham risk score , and prevalence of the metabolic syndrome ; only the changes in BMI and fat mass were different between worksites . CONCLUSION A multi-faceted worksite intervention promoted favorable changes in cardiovascular disease risk factors , but many of the improvements were achieved with worksite health assessment s and personalized health reports in the absence of an intervention", "Background Overweight and obesity have a dramatic negative impact on children 's health not only during the childhood but also throughout the adult life . Preventing the development of obesity in children is therefore a world-wide health priority . There is an obvious urge for sustainable and evidence d-based interventions that are suitable for families with young children , especially for families with overweight or obese parents . We have developed a prevention program , Early STOPP , combating multiple obesity-promoting behaviors such unbalanced diet , physical inactivity and disturbed sleeping patterns . We also aim to evaluate the effectiveness of the early childhood obesity prevention in a well-characterized population of overweight or obese parents . This protocol outlines methods for the recruitment phase of the study . Design and methods This r and omized controlled trial ( RCT ) targets overweight and /or obese parents with infants , recruited from the Child Health Care Centers ( CHCC ) within the Stockholm area . The intervention starts when infants are one year of age and continues until they are six and is regularly delivered by a trained coach ( dietitian , physiotherapist or a nurse ) . The key aspects of Early STOPP family intervention are based on Swedish recommendations for CHCC , which include advices on healthy food choices and eating patterns , increasing physical activity/reducing sedentary behavior and regulating sleeping patterns . Discussion The Early STOPP trial design addresses weaknesses of previous research by recruiting from a well-characterized population , defining a feasible , theory-based intervention and assessing multiple measurements to vali date and interpret the program effectiveness . The early years hold promise as a time in which obesity prevention may be most effective . To our knowledge , this longitudinal RCT is the first attempt to demonstrate whether an early , long-term , targeted health promotion program focusing on healthy eating , physical activity/reduced sedentary behaviors and normalizing sleeping patterns could be effective . If proven so , Early STOPP may protect children from the development of overweight and obesity . Trial registration The protocol for this study is registered with the clinical trials registry clinical trials.gov , ID : ES-2010", "OBJECTIVE To determine associations between younger youths ' susceptibility to smoking and four household variables related to tobacco socialization : parental and sibling smoking , restrictions on smoking in the home and exposure to smoking in vehicles . METHODS A secondary analysis of the 2004/05 Canadian Youth Smoking Survey used logistic regression to investigate the relationships between youth susceptibility to smoking , gender , and four household variables related to tobacco socialization . Susceptibility to smoking was operationalized by three levels of smoking experience and intention : non-susceptible non-smoker , susceptible non-smoker and experimenter/smoker . The national survey included 29 243 grade 5 to 9 students from r and omly sample d public and private schools in ten provinces . RESULTS For non-smokers , the odds of being susceptible to smoking increased with having a sibling who smokes , a lack of a total household smoking ban and riding in a vehicle with a smoker in the previous week , when adjusting for all other variables in the model . These variables also increased the odds of being an experimenter/smoker versus a susceptible non-smoker . Parent smoking status was not significant in these models . CONCLUSION Denormalization messages , through enforced home and vehicle smoking bans , appear to support youth in maintaining a resolve to not smoke , regardless of parental smoking status", "OBJECTIVE . The study tested whether a combined environmental and educational intervention solely promoting water consumption was effective in preventing overweight among children in elementary school . METHODS . The participants in this r and omized , controlled cluster trial were second- and third- grade rs from 32 elementary schools in socially deprived areas of 2 German cities . Water fountains were installed and teachers presented 4 prepared classroom lessons in the intervention group schools ( N = 17 ) to promote water consumption . Control group schools ( N = 15 ) did not receive any intervention . The prevalence of overweight ( defined according to the International Obesity Task Force criteria ) , BMI SD scores , and beverage consumption ( in glasses per day ; 1 glass was defined as 200 mL ) self-reported in 24-hour recall question naires , were determined before ( baseline ) and after the intervention . In addition , the water flow of the fountains was measured during the intervention period of 1 school year ( August 2006 to June 2007 ) . RESULTS . Data on 2950 children ( intervention group : N = 1641 ; control group : N = 1309 ; age , mean ± SD : 8.3 ± 0.7 years ) were analyzed . After the intervention , the risk of overweight was reduced by 31 % in the intervention group , compared with the control group , with adjustment for baseline prevalence of overweight and clustering according to school . Changes in BMI SD scores did not differ between the intervention group and the control group . Water consumption after the intervention was 1.1 glasses per day greater in the intervention group . No intervention effect on juice and soft drink consumption was found . Daily water flow of the fountains indicated lasting use during the entire intervention period , but to varying extent . CONCLUSION . Our environmental and educational , school-based intervention proved to be effective in the prevention of overweight among children in elementary school , even in a population from socially deprived areas", "This study investigated the effectiveness of labeling foods with the Choices nutrition logo on influencing cafeteria menu selection and the behavioral determinants of menu choices in work site cafeterias in the Netherl and s. A cluster r and omized controlled trial was conducted . Intervention cafeterias ( n=13 ) , where the Choices logo was used to promote healthier eating for a 3-week period , were compared with control cafeterias ( n=12 ) , which offered the same menu without the logo . Sales data were collected daily for 9 weeks , from March to May 2009 . In addition , employees from one intervention and one control company completed an online question naire at baseline and after the intervention ( n=368 ) in which the behavioral determinants of food choice ( ie , attitude , self-efficacy , and intention ) and logo use were measured . Generalized estimating equation analyses , χ² tests , t tests and linear regression analyses were performed . No nutritionally meaningful intervention effects were found in the sales of s and wiches , soups , snacks , fruit , and salads . Also , no significant differences in behavioral determinants were found . \" Intention to eat healthier \" and \" paying attention to product information \" were positively associated with self-reported consumption of foods with the Choices logo at lunch . The intervention did not have a significant effect on employees ' lunchtime food choices . Labeling healthy choices might be useful for health-conscious employees in the volitional phase of behavior change . Further research should focus on the possible health benefits of menu reformulation in the catering sector", "Objective : To investigate the effect of two contrasting physical activity worksite interventions versus a reference intervention ( REF ) on various health outcomes . Methods : A 1-year r and omized controlled trial was conducted with specific resistance training ( SRT ) , all-round physical exercise ( APE ) , and REF . Results : SRT and APE compared with REF showed significant reductions in systolic blood pressure ( ∼6 mm Hg ) , body fat percentage ( ∼2.2 body fat% ) , as well as shoulder and back pain ( ∼30 % reduction in duration ) . Muscle strength ( APE and SRT ) and maximal oxygen uptake ( APE ) increased approximately 10 % . Conclusions : Worksite intervention with both SRT as well as APE is recommended , since these activities compared with REF result ed in clinical ly relevant reductions of cardiovascular and metabolic syndrome-related risk factors as well as musculoskeletal pain symptoms , in combination with minor increases in physical capacity", "Background — The estimated effects of recent pubic and workplace smoking restriction laws suggest that they produce significant declines in community rates of heart attack . The consistency of these declines with existing estimates of the relative risk of heart attack in individuals attributable to passive smoking exposure is poorly understood . The objective is to determine the consistency of estimates of reductions in community rates of heart attacks result ing from smoking restriction laws with estimates of the relative risk of heart disease in individuals exposed to passive smoking . Methods and Results — Meta-analyses of existing estimates of declines in community rates were compared with a mathematical model of the relationship between individual risk and community rates . The outcome measure is the ratio of community rates of acute myocardial infa rct ion ( after divided by before implementation of a smoking restriction law ) . There is a significant drop in the rate of acute myocardial infa rct ion hospital admissions associated with the implementation of strong smoke-free legislation . The primary reason for heterogeneity in results of different studies is the duration of follow-up after adoption of the law . The pooled r and om-effects estimate of the rate of acute myocardial infa rct ion hospitalization 12 months after implementation of the law is 0.83 ( 95 % confidence interval , 0.80 to 0.87 ) , and this benefit grows with time . This drop in admissions is consistent with a range of plausible individual risk and exposure scenarios . Conclusion — Passage of strong smoke-free legislation produces rapid and substantial benefits in terms of reduced acute myocardial infa rct ions , and these benefits grow with time", "BACKGROUND Secondary school students often do not drink sufficient quantities of water during the school day to prevent dehydration , promote learning and good health . The study aim ed to measure the effect of health promotion and the free provision of cooled filtered water on the consumption of water and soft drinks . It also aim ed to explore students ' views of drinking water provision . METHODS A study was conducted with three secondary schools in North Tyneside . Over a 3 month period one school was given cooled filtered water and active promotion ( W + P ) , another had water only ( W ) . The control school ( C ) took part in post-intervention focus group work . RESULTS The average volume of water drunk by students , in school ' W + P ' was greater ( P = 0.05 ) than that drunk in school ' W ' and control school ' C ' . The volume of soft drinks purchased by students in all three schools before and during the intervention remained static . Focus group data revealed that students viewed their existing water provision as poor and wanted sufficient supplies of cooled filtered water in school . CONCLUSIONS This pilot study indicates that active promotion of water drinking increased consumption of water by secondary school students . Further developments of the project are suggested", "OBJECTIVES We examined the relationship between students ' tobacco use and the density and proximity of tobacco retailers near their schools . METHODS We used data from the 2003 - 2004 California Student Tobacco Survey and California retail licensing data . Measures included students ' self-reported tobacco use and geocoded state-reported locations of tobacco retailers . We used r and om-intercept generalized linear mixed modeling to jointly evaluate individual-level and school-level predictors . RESULTS Density of retailers was associated with experimental smoking ( odds ratio [ OR ] = 1.11 ; 95 % confidence interval [ CI ] = 1.02 , 1.21 ) but not established smoking ( OR = 1.06 ; 95 % CI = 0.94 , 1.20 ) . The effects on experimental smoking were confined to high school students ( OR = 1.17 ; 95 % CI = 1.06 , 1.29 ) in urban areas ( OR = 1.11 ; 95 % CI = 1.01 , 1.21 ) ; no effects were observed among middle school students or in rural schools . High school students were more likely to obtain cigarettes from a retailer ; middle school students relied more heavily on social sources . CONCLUSIONS Our results support the plausibility of reducing rates of students ' experimental smoking , but not established smoking , by restricting their access to commercial sources of tobacco in urban areas", "Objective : To assess the efficacy of a school-based intervention programme to reduce the prevalence of overweight in 6 to 10-year-old children . Design : Cluster-r and omized , controlled study .Subjects : A total of 3135 boys and girls in grade s 1–4 were included in the study . Methods : Ten schools were selected in Stockholm county area and r and omized to intervention ( n=5 ) and control ( n=5 ) schools . Low-fat dairy products and whole-grain bread were promoted and all sweets and sweetened drinks were eliminated in intervention schools . Physical activity ( PA ) was aim ed to increase by 30 min day−1 during school time and sedentary behaviour restricted during after school care time . PA was measured by accelerometry . Eating habits at home were assessed by parental report . Eating disorders were evaluated by self-report . Results : The prevalence of overweight and obesity decreased by 3.2 % ( from 20.3 to 17.1 ) in intervention schools compared with an increase of 2.8 % ( from 16.1 to 18.9 ) in control schools ( P analysis of BMI sds changes . However , a larger proportion of the children who were initially overweight reached normal weight in the intervention group ( 14 % ) compared with the control group ( 7.5 % ) , P=0.017 . PA did not differ between intervention and control schools after cluster adjustment . Eating habits at home were found to be healthier among families with children in intervention schools at the end of the intervention . There was no difference between children in intervention and control schools in self-reported eating disorders . Conclusions : A school-based intervention can reduce the prevalence of overweight and obesity in 6 to 10-year-old children and may affect eating habits at home . The effect of the intervention was possibly due to its effect on healthy eating habits at school and at home rather than on increased levels of PA ", "This paper measures tobacco polices in statewide representative sample s of secondary and mixed schools in Victoria , Australia and Washington , US ( N = 3,466 students from 285 schools ) and tests their association with student smoking . Results from confounder-adjusted r and om effects ( multi-level ) regression models revealed that the odds of student perception of peer smoking on school grounds are decreased in schools that have strict enforcement of policy ( odds ratio ( OR ) = 0.45 ; 95 % CI : 0.25 to 0.82 ; p = 0.009 ) . There was no clear evidence in this study that a comprehensive smoking ban , harsh penalties , remedial penalties , harm minimization policy or abstinence policy impact on any of the smoking outcomes", "OBJECTIVES This study examined the effects of pricing and promotion strategies on purchases of low-fat snacks from vending machines . METHODS Low-fat snacks were added to 55 vending machines in a convenience sample of 12 secondary schools and 12 worksites . Four pricing levels ( equal price , 10 % reduction , 25 % reduction , 50 % reduction ) and 3 promotional conditions ( none , low-fat label , low-fat label plus promotional sign ) were crossed in a Latin square design . Sales of low-fat vending snacks were measured continuously for the 12-month intervention . RESULTS Price reductions of 10 % , 25 % , and 50 % on low-fat snacks were associated with significant increases in low-fat snack sales ; percentages of low-fat snack sales increased by 9 % , 39 % , and 93 % , respectively . Promotional signage was independently but weakly associated with increases in low-fat snack sales . Average profits per machine were not affected by the vending interventions . CONCLUSIONS Reducing relative prices on low-fat snacks was effective in promoting lower-fat snack purchases from vending machines in both adult and adolescent population", "Background Front of pack food labels or signpost labels are currently widely discussed as means to help consumers to make informed food choices . It is hoped that more informed food choices will result in an overall healthier diet . There is only limited evidence , as to which format of a food label is best understood by consumers , helps them best to differentiate between more or less healthy food and whether these changes in perceived healthiness result in changes of food choice . Methods In a r and omised experimental study in Hamburg/Germany 420 adult subjects were exposed to one of five experimental conditions : ( 1 ) a simple \" healthy choice \" tick , ( 2 ) a multiple traffic light label , ( 3 ) a monochrome Guideline Daily Amount ( GDA ) label , ( 4 ) a coloured GDA label and ( 5 ) a \" no label \" condition . In the first task they had to identify the healthier food items in 28 pair-wise comparisons of foods from different food groups . In the second task they were asked to select food portions from a range of foods to compose a one-day 's consumption . Differences between means were analysed using ANOVAs . Results Task I : Experimental conditions differed significantly in the number of correct decisions ( p correct decisions ( 20.2 ± 3.2 ) , in the traffic light condition most correct decisions were made ( 24.8 ± 2.4 ) . Task II : Envisaged daily food consumption did not differ significantly between the experimental conditions . Conclusion Different food label formats differ in the underst and ing of consumers . The current study shows , that German adults profit most from the multiple traffic light labels . Perceived healthiness of foods is influenced by this label format most often . Nevertheless , such changes in perceived healthiness are unlikely to influence food choice and consumption . Attempts to establish the informed consumer with the hope that informed choices will be healthier choices are unlikely to change consumer behaviour and will not result in the desired contribution to the prevention of obesity and diet related diseases", "PURPOSE This study examined the association of objective and perceived neighborhood environmental characteristics and parent concerns with active commuting to school , investigated whether parental concerns varied by environmental characteristics , and compared the association of the perceived environment , parental concerns , and objective environment on the outcome active commuting to school . METHODS R and omly selected parents of children ( aged 5 - 18 yr ) , in neighborhoods chosen for their variability in objective ly measured walkability and income , completed question naires about their neighborhood environment , concerns about children walking to school , and children 's behavior ( N = 259 ) . Objective measures of the environment were available for each participant and each neighborhood . Logistic regression analyses were used to investigate the relationships among environment , parental concerns , and walking or biking to or from school at least once a week . RESULTS A parental concerns scale was most strongly associated with child active commuting ( odds ratio : 5.2 , 95 % CI : 2.71 - 9.96 ) . In high-income neighborhoods , more children actively commuted in high-walkable ( 34 % ) than in low-walkable neighborhoods ( 23 % ) ( odds ratio : 2.1 , 95 % CI : 1.12 - 3.97 ) , but no differences were noted in low-income neighborhoods . Parent concerns and neighborhood aesthetics were independently associated with active commuting . Perceived access to local stores and biking or walking facilities accounted for some of the effect of walkability on active commuting . CONCLUSION Both parent concerns and the built environment were associated with children 's active commuting to school . To increase active commuting to school , interventions that include both environmental change and education campaigns may be needed", "Increased visibility of food labels is a potential method to reduce the rate of obesity . However , few empirical studies have investigated the impact of nutrition labeling on food selection or energy intake . This study tested the hypothesis that nutrition labeling in combination with nutrition label education would promote reductions in energy intake using a laboratory-based paradigm . Forty-seven male ( n=24 ) and female ( n=23 ) participants visited the Nutrition and Health Research Laboratory for a single lunch session during the months of May through August 2009 . Participants were r and omly assigned to one of two video groups ( Nutrition Labeling Education or Organic Food Movement ) and one of two labeling conditions ( Nutrition Labels or No Labels ) . Participants watched a short educational video and then consumed a buffet lunch . Data were analyzed using a three-way analysis of covariance with sex , video condition , and labeling group as the between-subject factors and age and race as covariates . There were main effects of sex and nutrition label condition on lunch energy intake with females consuming less than males and people with nutrition labels consuming less energy than those without , regardless of sex or video condition . Examination of energy intake from low-energy-density and high-energy-density foods showed that the nutrition labeling group consumed less energy from both low-energy-density and high-energy-density food sources . These data support the use of nutrition labels as a way to reduce energy intake ", "Background Girl Scouting may offer a viable channel for health promotion and obesity prevention programs . This study evaluated the effectiveness of an intervention program delivered through Girl Scout Junior troops that was design ed to foster healthful troop meeting environments and increase obesity prevention behaviors at home . Methods Seven Girl Scout troops were r and omized to intervention ( n = 3 , with 34 girls ) or st and ard-care control ( n = 4 , with 42 girls ) conditions . Girls ranged in age from 9 to 13 years ( mean 10.5 years ) . Intervention troop leaders were trained to implement policies promoting physical activity ( PA ) and healthful eating opportunities at troop meetings , and to implement a curriculum promoting obesity-prevention behaviors at home . The primary outcome variable was child body mass index ( BMI ) z-score . Secondary outcomes included accelerometer-assessed PA levels in troop meetings , direct observations of snack offerings , time spent in physically active meeting content , and leader encouragement of PA and healthful eating . Results The intervention was delivered with good fidelity , and intervention troops provided greater opportunities for healthful eating and PA ( x2 = 210.8 , p PA ( x2 = 23.46 , p healthful eating ( x2 = 18.14 , p discouraged healthful eating and PA less frequently ( x2 = 9.63 , p = .002 ) compared to control troop leaders . Most effects of the intervention on individual-level variables of girls and parents were not significantly different from the control condition , including the primary outcome of child BMI z-score ( F1 , 5 = 0.42 , p = .544 ) , parent BMI ( F1 , 5 = 1.58 , p = .264 ) , and related behavioral variables . The notable exception was for objective ly assessed troop PA , wherein girls in intervention troops accumulated significantly less sedentary ( x2 = 6.3 , p = .011 ) , significantly more moderate ( x2 = 8.2 , p = .004 ) , and more moderate-to-vigorous physical activity , ( x2 = 18.4 , p < .001 ) , than girls in control troops . Conclusions Implementing a health promotion curriculum and supporting policies to provide more healthful environments in Girl Scout troop meetings appears feasible on a broader scale . Additional work is needed to bridge health promotion from such setting s to other environments if lasting individual-level behavior change and obesity prevention remain targeted outcomes . Trial registration number :", "Two pilot studies were conducted to examine whether 6th grade students can achieve moderate to vigorous physical activity ( MVPA ) from 1 ) activity-based physical education ( AB-PE ) with 585 participants and 2 ) a curricular-based ( CB-PE ) program with 1,544 participants and r and omly sample d heart rates during lessons . AB-PE participants spent between 54 - 66 % with a heart rate > 140 bpm . CB-PE participants spent between 49 - 58 % with a heart rate > 140 bpm . Girls ' mean heart rate was 3.7 bpm lower than the boys . PE can be readily modified so that students spend more than 50 % of time in MVPA", "BACKGROUND Recognizing the importance of smoking cessation after acute myocardial infa rct ion ( AMI ) , the Centers for Medicare & Medicaid Services and the Joint Commission on Accreditation of Healthcare Organizations currently uses documentation of smoking cessation counseling ( SCC ) as a metric of hospitals ' quality of AMI care . Yet , the association between hospitals ' performance of this quality measure and subsequent tobacco cessation rates has not been established . METHODS We analyzed 889 consecutive smokers treated for AMI at 19 hospitals in PREMIER ( Prospect i ve Registry Evaluating Myocardial Infa rct ion : Events and Recovery ) between January 1 , 2003 , and June 28 , 2004 . Patients were followed up for 1 year after hospitalization . Multivariate regression modeling was performed to determine the association between hospital-level documented SCC rates and tobacco cessation rates after discharge . RESULTS On a hospital level , the median medical record-documented SCC rate was 72.0 % ( interquartile range , 59.6%-90.1 % ) . At 1 year , the median smoking cessation rate was 55.6 % ( interquartile range , 37.5%-61.9 % ) . Although patients with documented SCC were more likely to recall receiving SCC at 1 month ( 86.1 % vs 70.8 % , P rate of quitting at 1 year was lower than that of patients without documented SCC ( 50.1 % vs 60.7 % , P = .02 ; relative risk , 0.76 ; 95 % confidence interval , 0.61 - 0.94 ) . At the hospital level , there was no correlation between SCC documentation and successful quitting at 6 months ( r = -0.19 , P = .11 ) or 1 year ( r = -0.13 , P = .45 ) . CONCLUSIONS The performance metric for SCC , as it is currently structured , does not correlate with actual smoking cessation at 6 months or 1 year . Revision of this performance measure should be considered to more effectively reflect the goal of promoting smoking cessation", "INTRODUCTION Legal restrictions have contributed to the decline in smoking prevalence in several European countries . We investigated the impact of the Italian 2005 indoor smoking ban on the efficacy of counseling alone or in combination with bupropion for smoking cessation . METHODS Before and after the introduction of the ban ( 2001 - 2006 ) , 550 smokers were enrolled in the smoking cessation program in Rome and were asked to choose between a 6-week group counseling therapy ( GCT ) given alone or in combination with 7 weeks of daily bupropion . Follow-up was completed 12 , 26 , and 52 weeks after the quit day . Due to the observational nature of the study , we used propensity scores to match 138 and 290 subjects ( pre-/postban ) in the bupropion- and GCT-only groups , respectively . RESULTS Covariate balance in the two matched sample s was adequate for all variables except \" coffee consumption \" in the GCT-only group . The regression adjusted odds ratios indicated that the introduction of the ban result ed in 52 % reduced odds of continued smoking at 12 months among the GCT + bupropion group and 41 % reduced odds in the GCT-only group . We observed that the ban was associated with both increased 12-month abstinence rates and motivation to quit . In a mediation analysis , we determined that the total effect of the smoking ban on the abstinence rate was reduced after controlling for motivation , which confirmed that motivation was a partial mediator . DISCUSSION The introduction of an indoor smoking ban improved the efficacy of smoking cessation treatments by possibly providing a setting that increased the level of motivation to stop smoking", "Background To evaluate the impact of a walking school bus ( WSB ) program on student transport in a low-income , urban neighborhood . Methods The design was a controlled , quasi-experimental trial with consecutive cross-sectional assessment s. The setting was three urban , socioeconomically disadvantaged , public elementary schools ( 1 intervention vs. 2 controls ) in Seattle , Washington , USA . Participants were ethnically diverse students in kindergarten-5th grade ( aged 5–11 years ) . The intervention was a WSB program consisting of a part-time WSB coordinator and parent volunteers . Students ' method of transportation to school was assessed by a classroom survey at baseline and one-year follow-up . The Pearson Chi-squared test compared students transported to school at the intervention versus control schools at each time point . Due to multiple testing , we calculated adjusted p-values using the Ryan-Holm stepdown Bonferroni procedure . McNemar 's test was used to examine the change from baseline to 12-month follow-up for walking versus all other forms of school transport at the intervention or control schools . Results At baseline , the proportions of students ( n = 653 ) walking to the intervention ( 20 % + /- 2 % ) or control schools ( 15 % + /- 2 % ) did not differ ( p = 0.39 ) . At 12-month follow up , higher proportions of students ( n = 643 , p = 0.001 ) ) walked to the intervention ( 25 % + /- 2 % ) versus the control schools ( 7 % + /- 1 % ) . No significant changes were noted in the proportion of students riding in a car or taking the school bus at baseline or 12-month follow up ( all p > 0.05 ) . Comparing baseline to 12-month follow up , the numbers of students who walked to the intervention school increased while the numbers of students who used the other forms of transport did not change ( p numbers of students who walked to the control schools decreased while the numbers of students who used the other forms of transport did not change ( p WSB program is a promising intervention among urban , low-income elementary school students that may promote favorable changes toward active transport to school . Trial Registration Clinical Trials.gov", "BACKGROUND Soaring obesity levels present a severe health risk in the United States , especially in low-income minority population s. INTERVENTION High-frequency paid television and radio advertising , as well as bus and streetcar signage . SETTING / PARTICIPANTS A mass media campaign in New Orleans to promote walking and fruit and vegetable consumption in a low-income , predominantly African-American urban population . Messages tailored with consideration of the African-American majority . DESIGN R and om-digit-dial telephone surveys using cross-sectional representative sample s at baseline in 2004 and following the onset of the campaign in 2005 . MEASURES Survey items on campaign message recall ; attitudes toward walking , snack food avoidance , and fruit and vegetable consumption ; and behaviors related to fruit and vegetable consumption , snack food consumption , and utilitarian and leisure walking . RESULTS From baseline , there were significant increases in message recall measures , positive attitudes toward fruit and vegetable consumption , and positive attitudes toward walking . Behaviors did not change significantly . In 2005 , message recall measures were associated with positive levels of each of the outcome variables . CONCLUSIONS Over 5 months , the media campaign appeared to have stimulated improvements in attitudes toward healthy diet and walking behaviors addressed by the campaign . These findings encourage the continuation of the media campaign , with future evaluation to consider whether the behavioral measures change", "OBJECTIVE To present the effects of a relatively modest environmental intervention on biological cardiovascular risk indicators . METHOD A controlled trial , including two worksites . Measurements ( i.e. , body composition , blood pressure and serum cholesterol ) took place at baseline and at 3- and 12-month follow-up . The 12-month environmental intervention ( The Hague , The Netherl and s , 2004 ) consisted of : a ' Food'-part : to stimulate healthier food choices by means of product information in the canteen , and a ' Steps'-part : focused on stimulating stair use by means of motivational prompts in staircases and on elevator doors . RESULTS Significant differences in change between groups ( n=540 ) in favor of the intervention group were found on : [ 1 ] total cholesterol for women ( -0.35 mmol/l ) ; [ 2 ] HDL for men at 3 months ( 0.05 mmol/l ) and 12 months ( 0.10 mmol/l ) ; and [ 3 ] the total-HDL ratio for the total intervention group at 3 and 12 months ( -0.45 mmol/l ) . Both groups showed a decrease in all body composition values at both follow-ups . A significant difference in change in systolic BP was found in favor of the control group ( approximately 4 mm Hg ) , due to an increase in the intervention group at both follow-ups . CONCLUSIONS Based on the contrasting results , this modest environmental intervention was ineffective in reducing cardiovascular risk in a population of office workers", "Taxation has been proposed as a means to reduce consumption of unhealthy food items . However , it is unknown if taxation without regulations or other activities known to shift eating behaviors lead to long-term dietary change . This unexplored issue is examined using data from the Russia Longitudinal Monitoring Survey . Data were from adults aged 25 - 55 y who participated in the nationally representative Russian Longitudinal Monitoring Survey . Twenty-four-hour dietary recalls , detailed food expenditure data , and community-level food prices collected over 1994 - 2005 were used for these analyses . Longitudinal r and om effects models were used to test the relation of time on the structure of diet while controlling for total household expenditures . The proportion of total energy consumed from fat was higher in all other years combined compared with 1998 ( P proportion of dietary fat from high-fat meat and high-fat dairy items were lowest in 1998 and increased over subsequent years despite increasing costs . Percent fat from fats and oils continued to decline with rising costs . Price changes led to substantial shifts in the structure of food consumption . However , except for the most expensive items , consumption of items returned to levels consumed in the former Soviet Union following price stabilization", "Background Built environment research is dominated by cross-sectional design s , which are particularly vulnerable to residential self- selection bias result ing from health-related attitudes , neighborhood preferences , or other unmeasured characteristics related to both neighborhood choice and health-related outcomes . Methods We used cohort data from the National Longitudinal Study of Adolescent Health ( United States ; Wave I , 1994 - 95 ; Wave III , 2001 - 02 ; n = 12,701 ) and a time-varying geographic information system . Longitudinal relationships between moderate to vigorous physical activity ( MVPA ) bouts and built and socioeconomic environment measures ( l and cover diversity , pay and public physical activity facilities per 10,000 population , street connectivity , median household income , and crime rate ) from adolescence to young adulthood were estimated using r and om effects models ( biased by unmeasured confounders ) and fixed effects models ( within-person estimator , which adjusts for unmeasured confounders that are stable over time ) . Results R and om effects models yielded None associations except for negative crime-MVPA associations [ coefficient ( 95 % CI ) : -0.056 ( -0.083 , -0.029 ) in males , -0.061 ( -0.090 , -0.033 ) in females ] . After controlling for measured and time invariant unmeasured characteristics using within-person estimators , MVPA was higher with greater physical activity pay facilities in males [ coefficient ( 95 % CI ) : 0.024 ( 0.006 , 0.042 ) ] , and lower with higher crime rates in males [ coefficient ( 95 % CI ) : -0.107 ( -0.140 , -0.075 ) ] and females [ coefficient ( 95 % CI ) : -0.046 ( -0.083 , -0.009 ) ] . Other associations were None or in the counter-intuitive direction . Conclusions Comparison of within-person estimates to estimates unadjusted for unmeasured characteristics suggest that residential self- selection can bias associations toward the None , as opposed to its typical characterization as a positive confounder . Differential environment-MVPA associations by residential relocation suggest that studies examining changes following residential relocation may be vulnerable to selection bias . The authors discuss complexities of adjusting for residential self- selection and residential relocation , particularly during the adolescent to young adult transition ", "OBJECTIVE On March 1st , 2008 a smoking ban in public buildings became effective in the Canton of Graubuenden , Switzerl and . The aim of our study was to investigate , whether implementation of this new regulation was followed by a decrease in the incidence of acute myocardial infa rct ion ( AMI ) . PATIENTS AND METHODS The Kantonsspital Graubuenden serves as a tertiary care hospital , possessing the only cardiac catheterization laboratory in the Canton of Graubuenden . Based on an excellent functioning network including all hospitals in the Canton of Graubuenden , virtually all patients experiencing an AMI in the Canton of Graubuenden are transferred to our hospital for either acute or early coronary angiography . Data of all patients with AMI undergoing coronary angiography at our hospital between March 1st , 2008 and February 28th , 2009 were collected prospect ively . The data were then compared with those of the two corresponding 12-month periods preceding implementation of the public smoking ban . RESULTS In the two years before adoption of smoke-free legislation , the number of patients with AMI was 229 and 242 , respectively ( p = ns ) . In the 12 months after implementation of the public smoking ban , the number of AMI patients dropped to 183 ( p AMI incidence within the first year after enactment of the new regulation . This reduction was driven by a significant decrease in the AMI incidence in men , nonsmokers , and individuals with established coronary artery disease , including those with prior AMI or prior percutaneous coronary intervention . CONCLUSIONS Similar to other countries in Europe and various regions of the USA and Canada , implementation of a public smoking ban was followed by a significant early decline in the incidence of AMI in the Canton of Graubuenden , Switzerl and", "Purpose . To examine associations of the built environment surrounding worksites and of work policies with walking behaviors . Design . Cross-sectional convenience sample survey . Setting . Workplace . Subjects . Employed adults residing in Montgomery County , Maryl and . Measures . Four different step measures taken at or near work as recorded using an accelerometer and a fifth measure indicated self-reported walking from work . Participants reported on eight built environment characteristics surrounding the worksite ( e.g. , the presence of sidewalks , crosswalks , and pedestrian signals ) and on four worksite policies ( e.g. , the presence of exercise facilities and exercise programs ) . Analysis . Cross-sectional associations of self-reported built environment characteristics surrounding worksites and worksite policies with walking behavior were examined . Results . Although participants reported worksites exhibiting built environment characteristics that were supportive of walking ( seven of eight characteristics were reported by > 50 % of participants ) , no built environment characteristic was associated with walking more than the median number of average weekday steps ( p > .05 ) . All four worksite policies were associated with walking more than the median number of average weekday steps ( p walking trip from work in the past month ( p employee walking . Future studies should consider a prospect i ve design and examine a larger , more diverse employee population and worksite environment to examine these associations", "BACKGROUND Smoking is the leading preventable cause of premature death in the United States . Previous studies of financial incentives for smoking cessation in work setting s have not shown that such incentives have significant effects on cessation rates , but these studies have had limited power , and the incentives used may have been insufficient . METHODS We r and omly assigned 878 employees of a multinational company based in the United States to receive information about smoking-cessation programs ( 442 employees ) or to receive information about programs plus financial incentives ( 436 employees ) . The financial incentives were $ 100 for completion of a smoking-cessation program , $ 250 for cessation of smoking within 6 months after study enrollment , as confirmed by a biochemical test , and $ 400 for abstinence for an additional 6 months after the initial cessation , as confirmed by a biochemical test . Individual participants were stratified according to work site , heavy or nonheavy smoking , and income . The primary end point was smoking cessation 9 or 12 months after enrollment , depending on whether initial cessation was reported at 3 or 6 months . Secondary end points were smoking cessation within the first 6 months after enrollment and rates of participation in and completion of smoking-cessation programs . RESULTS The incentive group had significantly higher rates of smoking cessation than did the information-only group 9 or 12 months after enrollment ( 14.7 % vs. 5.0 % , P Incentive-group participants also had significantly higher rates of enrollment in a smoking-cessation program ( 15.4 % vs. 5.4 % , P completion of a smoking-cessation program ( 10.8 % vs. 2.5 % , P smoking cessation within the first 6 months after enrollment ( 20.9 % vs. 11.8 % , P financial incentives for smoking cessation significantly increased the rates of smoking cessation . ( Clinical Trials.gov number , NCT00128375 .", "OBJECTIVE The objective was to test the hypothesis that a community-based environmental change intervention could prevent weight gain in young children ( 7.6 + /- 1.0 years ) . RESEARCH METHODS AND PROCEDURES A non-r and omized controlled trial was conducted in three culturally diverse urban cities in Massachusetts . Somerville was the intervention community ; two socio-demographically-matched cities were control communities . Children ( n = 1178 ) in grade s 1 to 3 attending public elementary schools participated in an intervention design ed to bring the energy equation into balance by increasing physical activity options and availability of healthful foods within the before- , during- , after-school , home , and community environments . Many groups and individuals within the community ( including children , parents , teachers , school food service providers , city departments , policy makers , healthcare providers , before- and after-school programs , restaurants , and the media ) were engaged in the intervention . The main outcome measure was change in BMI z-score . RESULTS At baseline , 44 % ( n = 385 ) , 36 % ( n = 561 ) , and 43 % ( n = 232 ) of children were above the 85th percentile for BMI z-score in the intervention and the two control communities , respectively . In the intervention community , BMI z-score decreased by -0.1005 ( p = 0.001 , 95 % confidence interval , -0.1151 to -0.0859 ) compared with children in the control communities after controlling for baseline covariates . DISCUSSION A community-based environmental change intervention decreased BMI z-score in children at high risk for obesity . These results are significant given the obesigenic environmental backdrop against which the intervention occurred . This model demonstrates promise for communities throughout the country confronted with escalating childhood obesity rates", "Cardiac rehabilitation and exercise training ( CRET ) provides health risk intervention in cardiac patients over a relatively short time frame . Worksite health programs offer a unique opportunity for health intervention , but these programs remain underused due to concerns over recouping the costs . We evaluated the clinical efficacy and cost-effectiveness of a 6-month worksite health intervention using staff from CRET . Employees ( n = 308 ) and spouses ( n = 31 ) of a single employer were r and omized to active intervention ( n = 185 ) consisting of worksite health education , nutritional counseling , smoking cessation counseling , physical activity promotion , selected physician referral , and other health counseling versus usual care ( n = 154 ) . Health risk status was assessed at baseline and after the 6-month intervention program , and total medical cl aim costs were obtained in all participants during the year before and the year after intervention . Significant improvements were demonstrated in quality -of-life scores ( + 10 % , p = 0.001 ) , behavioral symptoms ( depression -33 % , anxiety -32 % , somatization -33 % , and hostility -47 % , all p values body fat ( -9 % , p = 0.001 ) , high-density lipoprotein cholesterol ( + 13 % , p = 0.0001 ) , diastolic blood pressure ( -2 % , p = 0.01 ) , health habits ( -60 % , p = 0.0001 ) , and total health risk ( -25 % , p = 0.0001 ) . Of employees categorized as high risk at baseline , 57 % were converted to low-risk status . Average employee annual cl aim costs decreased 48 % ( p = 0.002 ) for the 12 months after the intervention , whereas control employees ' costs remained unchanged ( -16 % , p = NS ) , thus creating a sixfold return on investment . In conclusion , worksite health intervention using CRET staff decreased total health risk and markedly decreased medical cl aim costs within 12 months", "The effect of a smokers ' hotline as an adjunct to self-help manuals was examined . Subjects were 1,813 smokers recruited from a 10-county rural and small urban area . Counties were matched on demographic characteristics and assigned to a manual only or manual plus hotline condition . Subjects were followed over an 18-month period . Hotline services included taped messages and access to paraprofessional counselors . Results show a consistent , significant hotline effect across outcome measures and follow-up periods . This effect emerged either as a main effect for the hotline or as an interaction with enrollment method such that a significant hotline effect emerged for subjects who enrolled through face-to-face methods . These findings indicate the effectiveness of the hotline in enhancing self-help quit rates", "BACKGROUND Previous studies have suggested a reduction in the total number of hospital admissions for acute coronary syndrome after the enactment of legislation banning smoking in public places . However , it is unknown whether the reduction in admissions involved nonsmokers , smokers , or both . METHODS Since the end of March 2006 , smoking has been prohibited by law in all enclosed public places throughout Scotl and . We collected information prospect ively on smoking status and exposure to secondh and smoke based on question naires and biochemical findings from all patients admitted with acute coronary syndrome to nine Scottish hospitals during the 10-month period preceding the passage of the legislation and during the same period the next year . These hospitals accounted for 64 % of admissions for acute coronary syndrome in Scotl and , which has a population of 5.1 million . RESULTS Overall , the number of admissions for acute coronary syndrome decreased from 3235 to 2684 - -a 17 % reduction ( 95 % confidence interval , 16 to 18)--as compared with a 4 % reduction in Engl and ( which has no such legislation ) during the same period and a mean annual decrease of 3 % ( maximum decrease , 9 % ) in Scotl and during the decade preceding the study . The reduction in the number of admissions was not due to an increase in the number of deaths of patients with acute coronary syndrome who were not admitted to the hospital ; this latter number decreased by 6 % . There was a 14 % reduction in the number of admissions for acute coronary syndrome among smokers , a 19 % reduction among former smokers , and a 21 % reduction among persons who had never smoked . Persons who had never smoked reported a decrease in the weekly duration of exposure to secondh and smoke ( P concentration of serum cotinine from 0.68 to 0.56 ng per milliliter ( P number of admissions for acute coronary syndrome decreased after the implementation of smoke-free legislation . A total of 67 % of the decrease involved nonsmokers . However , fewer admissions among smokers also contributed to the overall reduction", "We surveyed 7318 customers from 275 r and omly selected restaurants of 11 fast food chains . Participants purchased a mean of 827 calories , with 34 % purchasing 1000 calories or more . Unlike other chains , Subway posted calorie information at point of purchase and its patrons more often reported seeing calorie information than patrons of other chains ( 32 % vs 4 % ; P purchased 52 fewer calories than did other Subway patrons ( P calorie information prominently at point of purchase , where it can be seen and used to inform purchases", "Objectives : To assess the effect on fruit and vegetable consumption , self reported , and psychological health of a “ natural experiment”—the introduction of large scale food retailing in a deprived Scottish community . Design : Prospect i ve quasi-experimental design comparing baseline and follow up data in an “ intervention ” community with a matched “ comparison ” community in Glasgow , UK . Participants : 412 men and women aged 16 or over for whom follow up data on fruit and vegetable consumption and GHQ-12 were available . Main outcome measures : Fruit and vegetable consumption in portions per day , poor self reported health , and poor psychological health ( GHQ-12 ) . Main results : Adjusting for age , sex , educational attainment , and employment status there was no population impact on daily fruit and vegetable consumption , self reported , and psychological health . There was some evidence for a net reduction in the prevalence of poor psychological health for residents who directly engaged with the intervention . Conclusions : Government policy has advocated using large scale food retailing as a social intervention to improve diet and health in poor communities . In contrast with a previous uncontrolled study this study did not find evidence for a net intervention effect on fruit and vegetable consumption , although there was evidence for an improvement in psychological health for those who directly engaged with the intervention . Although definitive conclusions about the effect of large scale retailing on diet and health in deprived communities can not be drawn from non-r and omised controlled study design s , evaluations of the impacts of natural experiments may offer the best opportunity to generate evidence about the health impacts of retail interventions in poor communities", "Objective : To assess the degree to which smokers living with a full household ban on smoking change their cessation related behaviour . Design , setting , and participants : Prospect i ve cohort study ; follow up of a population based cohort of 1133 smokers , identified from a 1997 telephone survey of adult Oregonians . After a median of 21 months , 565 were located and reinterviewed . Main outcome measures : Quit attempts , time until relapse , and smoking cessation , defined as seven day and 90 day sustained abstinence at follow up . Results : A full ban at baseline was associated with a doubling of the odds of a subsequent quit attempt ( odds ratio ( OR ) = 2.0 , 95 % confidence interval ( CI ) , 1.0 to 3.9 ) . Among respondents in the preparation stage at baseline ( intention to quit in the next month with a quit attempt in the previous year ) , a full ban was associated with a lower relapse rate ( hazard ratio = 0.5 ( 95 % CI , 0.2 to 0.9 ) ) , while for those in precontemplation/contemplation ( no intention to quit or intention to quit within the next six months , respectively ) , there was no significant association between full ban and relapse rate . For respondents in preparation , those with a full ban had over four times the odds of being in cessation for seven or more days before the follow up call ( OR = 4.4 ( 1.1 to 18.7 ) ) , but for those in precontemplation/contemplation , full bans were unrelated to cessation . Conclusions : Full household bans may facilitate cessation among smokers who are preparing to quit by increasing quit attempts . They may also prolong time to relapse among those smokers", "Objective : To model the health benefits and cost-effectiveness of banning television ( TV ) advertisements in Australia for energy-dense , nutrient-poor food and beverages during children 's peak viewing times . Methods : Benefits were modelled as changes in body mass index ( BMI ) and disability-adjusted life years ( DALYs ) saved . Intervention costs ( AUD$ ) were compared with future health-care cost offsets from reduced prevalence of obesity-related health conditions . Changes in BMI were assumed to be maintained through to adulthood . The comparator was current practice , the reference year was 2001 , and the discount rate for costs and benefits was 3 % . The impact of the withdrawal of non-core food and beverage advertisements on children 's actual food consumption was drawn from the best available evidence ( a r and omized controlled trial of advertisement exposure and food consumption ) . Supporting evidence was found in ecological relationships between TV advertising and childhood obesity , and from the effects of marketing bans on other products . A Working Group of stakeholders provided input into decisions surrounding the modelling assumptions and second-stage filters of ‘ strength of evidence ’ , ‘ equity ’ , ‘ acceptability to stakeholders ’ , ‘ feasibility of implementation ’ , ‘ sustainability ’ and ‘ side-effects ’ . Results : The intervention had a gross incremental cost-effectiveness ratio of AUD$ 3.70 ( 95 % uncertainty interval ( UI ) $ 2.40 , $ 7.70 ) per DALY . Total DALYs saved were 37 000 ( 95 % UI 16 000 , 59 000 ) . When the present value of potential savings in future health-care costs was considered ( AUD$ 300 m ( 95 % UI $ 130 m , $ 480 m ) , the intervention was ‘ dominant ’ , because it result ed in both a health gain and a cost offset compared with current practice . Conclusions : Although recognizing the limitations of the available evidence , restricting TV food advertising to children would be one of the most cost-effective population -based interventions available to governments today . Despite its economic credentials from a public health perspective , the initiative is strongly opposed by food and advertising industries and is under review by the current Australian government", "Background Physical activity and motor skills acquisition are of high importance for health-related prevention and a normal development in childhood . However , few intervention studies exist in preschool children focussing on an increase in physical activity and motor skills . Proof of positive effects is available but not consistent . Methods / Design The design , curriculum , and evaluation strategy of a cluster r and omised intervention study in preschool children are described in this manuscript . In the Prevention through Activity in Kindergarten Trial ( PAKT ) , 41 of 131 kindergartens of Wuerzburg and Kitzingen , Germany , were r and omised into an intervention and a control group by a r and om number table stratified for the location of the kindergarten in an urban ( more than 20.000 inhabitants ) or rural area . The aims of the intervention were to increase physical activity and motor skills in the participating children , and to reduce health risk factors as well as media use . The intervention was design ed to involve children , parents and teachers , and lasted one academic year . It contained daily 30-min sessions of physical education in kindergarten based on a holistic pedagogic approach termed the \" early psychomotor education \" . The sessions were instructed by kindergarten teachers under regular supervision by the research team . Parents were actively involved by physical activity homework cards . The kindergarten teachers were trained in workshops and during the supervision . Assessment s were performed at baseline , 3 - 5 months into the intervention , at the end of the intervention and 2 - 4 months after the intervention . The primary outcomes of the study are increases in physical activity ( accelerometry ) and in motor skills performance ( composite score of obstacle course , st and ing long jump , balancing on one foot , jumping sidewise to and fro ) between baseline and the two assessment s during the intervention . Secondary outcomes include decreases in body adiposity ( BMI , skin folds ) , media use ( question naire ) , blood pressure , number of accidents and infections ( question naire ) , increases in specific motor skills ( throwing , balancing , complex motor performance , jumping ) and in flexibility . Discussion If this trial proofs the effectiveness of the multilevel kindergarten based physical activity intervention on preschooler 's activity levels and motor skills , the programme will be distributed nationwide in Germany . Trial Registration Clinical Trials.gov Identifier :", "Interventions to promote physical activity are important in preventing children from becoming overweight . Many projects have been developed but only a few showed ( moderate ) effects . JUMP-in is a systematic ally developed primary -school-based intervention that focuses on the use of theory , environmental changes , parental influences and cooperation with multi-level parties in intervention development . The effects of JUMP-in were evaluated with a quasi-experimental pre-test/post-test research design . In total , 510 children from Grade s 4 , 5 and 6 of four intervention schools and two control schools in Amsterdam were followed for an intervention period of one school year . Changes in physical activity as well as in the social cognitive determinants were assessed using self-reports . In addition , a process evaluation has been executed . The results show that JUMP-in was effective in influencing physical activity , especially among children from Grade 6 . Children in the control group decreased their level of physical activity considerably , while activity levels in intervention children from Grade 6 remained stable . The intervention effects could not be explained by changes in the measured social cognitive determinants . In contrast , process information illuminated differences in intervention effects between the participating schools . The results from the JUMP-in study show the importance of intervention design s that focus on a theory-based mix of relevant environmental and social cognitive factors", "BACKGROUND AND OBJECTIVES To examine the long term impact of workplace smoking bans on employee smoking cessation and relapse . Over three years we studied a total of 1033 current or former smokers ( intervention group ) employed in smoke-free hospitals and 816 current or former smokers ( comparison group ) employed in non-smoke-free workplaces . The design of this natural experiment is a prospect i ve cohort study . We r and omly selected both hospitals and employees from 12 strata based on hospital size and state tobacco regulations , and sample d employees in the same communities . Main outcome measures were post-ban quit ratio and relapse rate . RESEARCH DESIGN Between groups comparisons were conducted using the Cochran-Mantel-Haenszel statistic for general association , stratified Cox proportional hazards models , and the CMH analysis of variance statistic based on ranks . McNemar 's test and the sign test were used to test for changes over time within each group . RESULTS Differences in the post-ban quit ratio were observed between intervention and comparison groups ( p ⩽ 0.02 ) . For employees whose bans were implemented at least seven years before survey , the post-ban quit ratio was estimated at 0.256 , compared with 0.142 for employees in non-smoke-free workplaces ( p = 0.02 ) . After controlling for a variety of factors , time to quit smoking was shorter for the hospital employees ( p , relapse rates were similar between the groups . CONCLUSION Employees in workplaces with smoking bans have higher rates of smoking cessation than employees where smoking is permitted , but relapse is similar between these two groups of employees . The results of this investigation have international applicability for policy makers , clinicians , employers , and employees . Countries should review smoking policies in workplaces in light of their own smoking patterns and efforts to deal with environmental tobacco smoke", "Introduction Although several studies suggest that drinking water may help prevent obesity , no US studies have examined the effect of school drinking water provision and promotion on student beverage intake . We assessed the acceptability , feasibility , and outcomes of a school-based intervention to improve drinking water consumption among adolescents . Methods The 5-week program , conducted in a Los Angeles middle school in 2008 , consisted of providing cold , filtered drinking water in cafeterias ; distributing reusable water bottles to students and staff ; conducting school promotional activities ; and providing education . Self-reported consumption of water , nondiet soda , sports drinks , and 100 % fruit juice was assessed by conducting surveys among students ( n = 876 ) , preintervention and at 1 week and 2 months postintervention , from the intervention school and the comparison school . Daily water ( in gallons ) distributed in the cafeteria during the intervention was recorded . Results After adjusting for sociodemographic characteristics and baseline intake of water at school , the odds of drinking water at school were higher for students at the intervention school than students at the comparison school . Students from the intervention school had higher adjusted odds of drinking water from fountains and from reusable water bottles at school than students from the comparison school . Intervention effects for other beverages were not significant . Conclusion Provision of filtered , chilled drinking water in school cafeterias coupled with promotion and education is associated with increased consumption of drinking water at school . A r and omized controlled trial is necessary to assess the intervention 's influence on students ' consumption of water and sugar-sweetened beverages , as well as obesity-related outcomes", "Objective To assess the effectiveness of a school based physical activity programme during one school year on physical and psychological health in young schoolchildren . Design Cluster r and omised controlled trial . Setting 28 classes from 15 elementary schools in Switzerl and r and omly selected and assigned in a 4:3 ratio to an intervention ( n=16 ) or control arm ( n=12 ) after stratification for grade ( first and fifth grade ) , from August 2005 to June 2006 . Participants 540 children , of whom 502 consented and presented at baseline . Intervention Children in the intervention arm ( n=297 ) received a multi-component physical activity programme that included structuring the three existing physical education lessons each week and adding two additional lessons a week , daily short activity breaks , and physical activity homework . Children ( n=205 ) and parents in the control group were not informed of an intervention group . For most outcome measures , the assessors were blinded . Main outcome measures Primary outcome measures included body fat ( sum of four skinfolds ) , aerobic fitness ( shuttle run test ) , physical activity ( accelerometry ) , and quality of life ( question naires ) . Secondary outcome measures included body mass index and cardiovascular risk score ( average z score of waist circumference , mean blood pressure , blood glucose , inverted high density lipoprotein cholesterol , and triglycerides ) . Results 498 children completed the baseline and follow-up assessment s ( mean age 6.9 ( SD 0.3 ) years for first grade , 11.1 ( 0.5 ) years for fifth grade ) . After adjustment for grade , sex , baseline values , and clustering within classes , children in the intervention arm compared with controls showed more negative changes in the z score of the sum of four skinfolds ( −0.12 , 95 % confidence interval −0.21 to −0.03 ; P=0.009 ) . Likewise , their z scores for aerobic fitness increased more favourably ( 0.17 , 0.01 to 0.32 ; P=0.04 ) , as did those for moderate-vigorous physical activity in school ( 1.19 , 0.78 to 1.60 ; P ( 0.44 , 0.05 to 0.82 ; P=0.03 ) , and total physical activity in school ( 0.92 , 0.35 to 1.50 ; P=0.003 ) . Z scores for overall daily physical activity ( 0.21 , −0.21 to 0.63 ) and physical quality of life ( 0.42 , −1.23 to 2.06 ) as well as psychological quality of life ( 0.59 , −0.85 to 2.03 ) did not change significantly . Conclusions A school based multi-component physical activity intervention including compulsory elements improved physical activity and fitness and reduced adiposity in children . Trial registration Current Controlled Trials IS RCT N15360785", "BACKGROUND . The prevalence and seriousness of childhood obesity has prompted calls for broad public health solutions that reach beyond clinic setting s. Schools are ideal setting s for population -based interventions to address obesity . OBJECTIVE . The purpose of this work was to examine the effects of a multicomponent , School Nutrition Policy Initiative on the prevention of overweight ( 85.0th to 94.9th percentile ) and obesity ( > 95.0th percentile ) among children in grade s 4 through 6 over a 2-year period . METHODS . Participants were 1349 students in grade s 4 through 6 from 10 schools in a US city in the Mid-Atlantic region with ≥50 % of students eligible for free or reduced-price meals . Schools were matched on school size and type of food service and r and omly assigned to intervention or control . Students were assessed at baseline and again after 2 years . The School Nutrition Policy Initiative included the following components : school self- assessment , nutrition education , nutrition policy , social marketing , and parent outreach . RESULTS . The incidences of overweight and obesity after 2 years were primary outcomes . The prevalence and remission of overweight and obesity , BMI z score , total energy and fat intake , fruit and vegetable consumption , body dissatisfaction , and hours of activity and inactivity were secondary outcomes . The intervention result ed in a 50 % reduction in the incidence of overweight . Significantly fewer children in the intervention schools ( 7.5 % ) than in the control schools ( 14.9 % ) became overweight after 2 years . The prevalence of overweight was lower in the intervention schools . No differences were observed in the incidence or prevalence of obesity or in the remission of overweight or obesity at 2 years . CONCLUSION . A multicomponent school-based intervention can be effective in preventing the development of overweight among children in grade s 4 through 6 in urban public schools with a high proportion of children eligible for free and reduced-priced school meals", "The study aim ed to assess the characteristics and reported behaviour change of participants in the BBC 's ' Fighting Fat , Fighting Fit ' ( FFFF ) campaign . A postal question naire survey was sent to a r and om sample of 6000 adults registering with the FFFF campaign at the start of the campaign and 5 months later . Demographic characteristics , weight , eating behaviour and activity patterns were assessed . In total , 3661 respondents completed the baseline question naire and 2112 ( 58 % ) of these completed a follow-up evaluation question naire 5 months later . The majority of evaluation participants were women and classified as ' overweight ' or ' obese ' . Participants reported significant reductions in weight , and in fat and snack intake , and significant increases in exercise levels , and in fruit , vegetable and starch intake during the 6 months of the campaign . These effects remained significant if non-responders were assumed to have made no change . These results show that mass-media campaigns might make a contribution to weight control at the population level , but particular subgroups such as men and people under 25 may require specifically targeted campaigns . In addition , whilst such campaigns may initially attract obese people , they may be more likely to drop out of the campaign than overweight and normal weight individuals", "STUDY OBJECTIVE : The aim of this study was to evaluate the impact of a smoke free programme implemented at the University of Geneva , Switzerl and , in 1996 . This programme included a prohibition to smoke in university buildings everywhere except in limited areas , and a smoking cessation counselling service . METHODS : Surveys were conducted before and four months after the programme was implemented , in representative sample s of programme participants ( n = 833 ) and university members not exposed to the programme ( n = 1023 ) . RESULTS : In retrospective assessment s , participants reported being less bothered by environmental tobacco smoke after programme implementation , but no between group difference was detected in prospect i ve assessment s. Relationships between smokers and non-smokers improved moderately in the intervention group and remained unchanged in the comparison group ( between group p = 0.001 ) . Proportions of smokers who attempted to quit smoking in the past four months increased from 2.0 % to 3.8 % in the intervention group and remained unchanged at 3.5 % in the comparison group ( between group difference : p = 0.048 ) . No impact on smoking prevalence ( 25 % ) was detected . The programme was appreciated by university members , although some of its modalities were criticised . CONCLUSION : A regulation prohibiting smoking everywhere but in limited areas of university buildings was acceptable and reduced the perception of bother by environmental tobacco smoke . It did not , however , influence smoking habits or attitudes toward smoking", "The purpose of this study was to comprehensively assess the impact of school tobacco policy intention , implementation and students ' perceptions of policy enforcement on smoking rates and location of tobacco use during the school day . Data were obtained from all students in Grade s 10 - 11 ( n = 22,318 ) in 81 r and omly selected schools from five Canadian provinces . Policy intention was assessed by coding written school tobacco policies . School administrators most familiar with the tobacco policy completed a survey to assess policy implementation . Results revealed policy intention and implementation subscales did not significantly predict school smoking prevalence but result ed in moderate prediction of tobacco use on school property ( R(2 ) = 0.21 - 0.27 ) . Students ' perceptions of policy enforcement significantly predicted school smoking prevalence ( R(2 ) = 0.36 ) and location of tobacco use ( R(2 ) = 0.23 - 0.63 ) . The research findings emphasize : ( i ) the need to consider both written policy intention and actual policy implementation and ( ii ) the existence of a policy is not effective in controlling tobacco use unless the policy is implemented and is perceived to be strongly enforced", "PURPOSE This study evaluated the effects of a classroom-based physical activity program on children 's in-school physical activity levels and on-task behavior during academic instruction . METHODS Physical activity of 243 students was assessed during school hours . Intervention-group students ( N = 135 ) received a classroom-based program ( i.e. , Energizers ) . The control group ( N = 108 ) did not receive Energizers . On-task behavior during academic instruction time was observed for 62 third- grade ( N = 37 ) and fourth- grade students ( N = 25 ) before and after Energizers activities . An independent groups t-test compared in-school physical activity levels between intervention and control classes . A multiple-baseline across-classrooms design was used to evaluate the effectiveness of the Energizers on on-task behavior . Additionally , a two-way ( time [ pre- vs postobservation ] x period [ baseline vs intervention ] ) repeated- measures analysis of variance compared on-task behavior between observation periods . Magnitudes of mean differences were evaluated with Cohen 's delta ( ES ) . RESULTS Students in the intervention group took significantly ( P in-school steps ( 5587 + /- 1633 ) than control-group students ( 4805 + /- 1543 ) , and the size of this difference was moderate ( ES = 0.49 ) . The intervention was effective in improving on-task behavior ; after the Energizers were systematic ally implemented , on-task behavior systematic ally improved . The improvement in on-task behavior of 8 % between the pre-Energizers and post-Energizers observations was statistically significant ( P on-task behavior by 20 % after Energizers activities . This improvement was statistically significant ( P classroom-based physical activity program was effective for increasing daily in-school physical activity and improving on-task behavior during academic instruction", "OBJECTIVE To investigate longitudinal associations between community-level gasoline price and physical activity ( PA ) . METHOD In the Coronary Artery Risk Development in Young Adults study , 5115 black and white participants aged 18 - 30 at baseline 1985 - 86 were recruited from four U.S. cities ( Birmingham , Chicago , Minneapolis and Oakl and ) and followed over time . We used data from 3 follow-up exams : 1992 - 93 , 1995 - 96 , and 2000 - 01 , when the participants were located across 48 states . From question naire data , a total PA score was summarized in exercise units ( EU ) based on intensity and frequency of 13 PA categories . Using Geographic Information Systems , participants ' residential locations were linked to county-level inflation-adjusted gasoline price data collected by the Council for Community & Economic Research . We used a r and om-effect longitudinal regression model to examine associations between time-varying gasoline price and time-varying PA , controlling for age , race , gender , baseline study center , and time-varying education , marital status , household income , county cost of living , county bus fare , census block-group poverty , and urbanicity . RESULTS Holding all control variables constant , a 25-cent increase in inflation-adjusted gasoline price was significantly associated with an increase of 9.9 EU in total PA ( 95 % CI : 0.8 - 19.1 ) . CONCLUSION Rising prices of gasoline may be associated with an unintended increase in leisure PA", "BACKGROUND The built environment in which a person lives and works is thought to have a strong influence on his or her level of physical activity . However , this belief is largely based on cross-sectional studies underlining the need for prospect i ve studies using natural experiments . DESIGN This study adopted a quasi-experimental research design with multiple control neighborhoods and was conducted between 2005 and 2007 . Data were analyzed in 2008 . SETTING / PARTICIPANTS The subjects were children , adolescents , and adults in free-living conditions within one experimental and two control neighborhoods . INTERVENTION An urban greenway/trail was retrofitted in a neighborhood that lacked connectivity of the residential pedestrian infrastructure to nonresidential destinations . MAIN OUTCOME MEASURES The main outcomes were 2-hour counts of directly observed physical activity in the general neighborhood and , at the school level , active transport to school . RESULTS At the neighborhood level , the 2-hour counts of physical activity significantly increased between 2005 and 2007 ( p=0.000 ) in the intervention neighborhood , with a median increase of 8.0 counts . The control neighborhoods had a significant decrease in counts ( p=0.000 ) . The pre- and post-intervention changes between experimental and control neighborhoods were significantly different for total physical activity ( p=0.001 ) ; walking ( p=0.001 ) ; and cycling ( p=0.038 ) . There was no noted change over time for active transport to school in either the intervention or control neighborhoods . CONCLUSIONS Changes to the pedestrian connectivity of the built environment infrastructure may lead to greater levels of physical activity . However , this positive effect was limited to physical activity at the neighborhood level and not to active transport to school", "BACKGROUND Physical Activity Across the Curriculum ( PAAC ) was a three-year cluster r and omized controlled trial to promote physical activity and diminish increases in overweight and obesity in elementary school children . METHODS Twenty-four elementary schools were cluster r and omized to the Physical Activity Across the Curriculum intervention or served as control . All children in grade s two and three were followed to grade s four and five . Physical Activity Across the Curriculum promoted 90 min/wk of moderate to vigorous intensity physically active academic lessons delivered by classroom teachers . Body Mass Index was the primary outcome , daily Physical activity and academic achievement were secondary outcomes . RESULTS The three-year change in Body Mass Index for Physical Activity Across the Curriculum was 2.0+/-1.9 and control 1.9+/-1.9 , respectively ( NS ) . However , change in Body Mass Index from baseline to 3 years was significantly influenced by exposure to Physical Activity Across the Curriculum . Schools with > or = 75 min of Physical Activity Across the Curriculum/wk showed significantly less increase in Body Mass Index at 3 years compared to schools that had Physical Activity Across the Curriculum schools had significantly greater changes in daily Physical activity and academic achievement scores . CONCLUSIONS The Physical Activity Across the Curriculum approach may promote daily Physical activity and academic achievement in elementary school children . Additionally , 75 min of Physical Activity Across the Curriculum activities may attenuate increases in Body Mass Index", "Objective : To examine whether adolescents ’ exposure to youth smoking prevention ads sponsored by tobacco companies promotes intentions to smoke , curiosity about smoking , and positive attitudes toward the tobacco industry . Design : A r and omised controlled experiment compared adolescents ’ responses to five smoking prevention ads sponsored by a tobacco company ( Philip Morris or Lorillard ) , or to five smoking prevention ads sponsored by a non-profit organisation ( the American Legacy Foundation ) , or to five ads about preventing drunk driving . Setting : A large public high school in California ’s central valley . Subjects : A convenience sample of 9th and 10th grade rs ( n = 832 ) ages 14–17 years . Main outcome measures : Perceptions of ad effectiveness , intention to smoke , and attitudes toward tobacco companies measured immediately after exposure . Results : As predicted , adolescents rated Philip Morris and Lorillard ads less favourably than the other youth smoking prevention ads . Adolescents ’ intention to smoke did not differ as a function of ad exposure . However , exposure to Philip Morris and Lorillard ads engendered more favourable attitudes toward tobacco companies . Conclusions : This study demonstrates that industry sponsored anti-smoking ads do more to promote corporate image than to prevent youth smoking . By cultivating public opinion that is more sympathetic toward tobacco companies , the effect of such advertising is likely to be more harmful than helpful to youth ", "OBJECTIVE To investigate the differential association between neighborhood-level street network with walking , bicycling , and jogging by urbanicity and gender . METHODS We used prospect i ve data from 4 repeated exams on 5115 young adults recruited in 1985 - 1986 , followed through 2000 - 2001 , with self-reported walking , bicycling , and jogging . Using a Geographic Information System , we spatially and temporally linked time-varying residential locations to street network data within a 1 km Euclidean buffer . Two-part marginal effect modeling assessed longitudinal associations between neighborhood-level street network with walking , bicycling , and jogging , by urbanicity and gender , controlling for time-varying individual- and census-level covariates . RESULTS Neighborhood street density was positively associated with walking , bicycling , and jogging in low urbanicity areas , but in middle and high urbanicity areas , these associations became None ( men ) or inverse ( women ) . CONCLUSION Characteristics of neighborhood streets may influence adult residents ' walking , bicycling , and jogging , particularly in less urban areas . This research may inform policy efforts to encourage physical activity", "OBJECTIVE To determine the association between household participation in a community garden and fruit and vegetable consumption among urban adults . DESIGN Data were analyzed from a cross-sectional r and om phone survey conducted in 2003 . A quota sampling strategy was used to ensure that all census tracts within the city were represented . SETTING Flint , Michigan . PARTICIPANTS 766 adults . VARIABLES MEASURED Fruit and vegetable intake was measured using question naire items from the Behavioral Risk Factor Surveillance System . Household participation in a community garden was assessed by asking the respondent if he or she , or any member of the household , had participated in a community garden project in the last year . ANALYSIS Generalized linear models and logistic regression models assessed the association between household participation in a community garden and fruit and vegetable intake , controlling for demographic , neighborhood participation , and health variables . RESULTS Adults with a household member who participated in a community garden consumed fruits and vegetables 1.4 more times per day than those who did not participate , and they were 3.5 times more likely to consume fruits and vegetables at least 5 times daily . CONCLUSIONS AND IMPLICATION S Household participation in a community garden may improve fruit and vegetable intake among urban adults", "BACKGROUND Evidence that demonstrates the harmful effect of cigarette smoking during young adulthood is limited . Therefore , we assessed associations between cigarette smoking and several self-reported illnesses in a prospect i ve cohort study in healthy young adults . METHODS Data were derived from 4472 adults aged 18 to 30 years at baseline participants in the Coronary Artery Risk Development in Young Adults ( CARDIA ) study and reexamined at least once after 7 , 10 , or 15 years . RESULTS Cigarette smoking in 1985 - 86 was related to self-reported smoking-related cancers , circulatory disease , and peptic ulcer . Incidence of these diseases was 9.3/1000 person years among current smokers vs. 4.5/1000 person years among never smokers with no exposure to passive smoke , relative risk ( adjusted for race , sex , education , and center ) 1.96 ( 1.42 - 2.70 ) . Assuming causal relationships , 32 % of these premature incidents were attributable to smoking . The relative risks of liver disease , migraine headache , depression , being ill the day before the examination , and chronic cough and phlegm production were also higher in smokers . CONCLUSIONS Smokers aged 18 - 30 followed for 7 to 15 years reported an excess of both major and minor ailments related to earlier and current smoking . Thus , prevention , cessation , and avoiding passive smoking should remain strong goals among young people", "OBJECTIVES Legislation to ban smoking in public places is currently a major area of interest across Canada . The main objectives of the study were to 1 ) determine the effect of the smoking ban on incidence of acute myocardial infa rct ion , 2 ) determine if the new legislation altered population -based smoking prevalence , and 3 ) measure public support for the public smoking ban . METHODS The city of Saskatoon initiated a public smoking ban on July 1 , 2004 . We retrospectively review ed all hospital discharges for acute MI from July 2000 to June 2005 . We review ed CCHS survey information on smoking prevalence for Saskatoon , Saskatchewan and Canada from 2003 to 2005 . We prospect ively contacted 1,255 Saskatoon residents by telephone to determine support for the public smoking ban . RESULTS The age-st and ardized incidence rate of acute MI fell from 176.1 ( 95 % CI 165.3 - 186.8 ) cases per 100,000 population ( July 1 , 2000 to June 30 , 2004 ) to 152.4 ( 95 % CI 135.3 - 169.3 ) cases per 100,000 population ( July 1 , 2004 to June 30 , 2005 ) . Smoking prevalence in Saskatoon fell from 24.1 % in 2003 ( 95 % CI 20.4 - 27.7 ) to 18.2 % in 2005 ( 95 % CI 15.7 - 20.9 ) while smoking prevalence in Saskatchewan remained unchanged at 23.8 % ( 95 % CI 22.6 - 25.3 ) and Canada reduced from 22.9 % ( 95 % CI 22.5 - 23.3 ) to 21.3 % ( 95 % CI 20.8 - 21.8 ) . Seventy-nine percent of Saskatoon residents believed the smoking ban was a good idea . INTERPRETATION The public smoking ban in Saskatoon , Canada , is associated with reduced incidence rates of acute MI , lower smoking prevalence and high levels of public support", "BACKGROUND Currently , there is little underst and ing of the relationship between the strength of workplace smoking policies and the likelihood and duration , not just the likelihood , of exposure to secondh and smoke at work . METHODS This study assessed self-reported exposure to secondh and smoke at work in hours per week among a cross-sectional sample of 3650 Massachusetts adults who were employed primarily at a single worksite outside the home that was not mainly outdoors . The sample data were from a larger longitudinal study design ed to examine the effect of community-based tobacco control interventions on adult and youth smoking behavior . Participants were identified through a r and om-digit-dialing telephone survey . Multiple logistic regression and zero-inflated negative binomial regression models were used to estimate the independent effect of workplace smoking policies on the likelihood and duration of exposure to secondh and smoke . RESULTS Compared to employees whose workplace banned smoking completely , those whose workplace provided design ated smoking areas had 2.9 times the odds of being exposed to secondh and smoke and 1.74 times the duration of exposure , while those with no restrictions had 10.27 times the odds of being exposed and 6.34 times the duration of exposure . CONCLUSIONS Workplace smoking policies substantially reduce the likelihood of self-reported secondh and smoke exposure among employees in the workplace and also greatly affect the duration of exposure", "BACKGROUND Formal efforts to recruit smokers into cessation programs have failed to reach large segments of the smoking population . Telephone intervention may represent a viable strategy to promote smoking cessation . An even more promising approach may be a combination of brief telephone support and outreach to identified smokers . METHODS Telephone support for smoking cessation was provided to four identified smoker population s in Bloomington , Minn , one of three Minnesota Heart Health Program education communities . Smokers were r and omly assigned to an intervention consisting of two 15-minute telephone calls approximately 1 to 3 weeks apart or to a nonintervention control . RESULTS At the 6-month follow-up , a significant overall effect was found in favor of the intervention condition for both self-reported and cotinine-vali date d quitting . Differences between intervention and control conditions were no longer significant at 18 months . CONCLUSIONS Smokers ' receptivity to telephone intervention was at least moderately encouraging . The cost of intervention could be relatively low if trained volunteers initiated telephone calls . However , more intensive telephone intervention and support may be needed to produce lasting changes in smoking prevalence", "Background : Be Active Eat Well ( BAEW ) was a multifaceted community capacity-building program promoting healthy eating and physical activity for children ( aged 4–12 years ) in the Australian town of Colac . Objective : To evaluate the effects of BAEW on reducing children 's unhealthy weight gain . Methods : BAEW had a quasi-experimental , longitudinal design with anthropometric and demographic data collected on Colac children in four preschools and six primary schools at baseline ( 2003 , n=1001 , response rate : 58 % ) and follow-up ( 2006 , n=839 , follow-up rate : 84 % ) . The comparison sample was a stratified r and om selection of preschools ( n=4 ) and primary schools ( n=12 ) from the rest of the Barwon South Western region of Victoria , with baseline assessment in 2003–2004 ( n=1183 , response rate : 44 % ) and follow-up in 2006 ( n=979 , follow-up rate : 83 % ) . Results : Colac children had significantly lower increases in body weight ( mean : −0.92 kg , 95 % CI : −1.74 to −0.11 ) , waist ( −3.14 cm , −5.07 to −1.22 ) , waist/height ( −0.02 , −0.03 to −0.004 ) , and body mass index z-score ( −0.11 , −0.21 to −0.01 ) than comparison children , adjusted for baseline variable , age , height , gender , duration between measurements and clustering by school . In Colac , the anthropometric changes were not related to four indicators of socioeconomic status ( SES ) , whereas in the comparison group 19/20 such analyses showed significantly greater gains in anthropometry in children from lower SES families . Changes in underweight and attempted weight loss were no different between the groups . Conclusions : Building community capacity to promote healthy eating and physical activity appears to be a safe and effective way to reduce unhealthy weight gain in children without increasing health inequalities", "During the 1980s three comprehensive community-based heart disease prevention trials were conducted in the United States . The Stanford Five-City Project , Minnesota Heart Health Program , and Pawtucket Heart Health Program involved 12 cities ; six received a 5 - 8 year multifactorial risk reduction program . This analysis pools data from the three studies to delineate the common intervention effects with greater sample size and power than could be attained by the single studies . Time trends were estimated for cigarette smoking , blood pressure , total cholesterol , body mass index , and coronary heart disease mortality risk in women and men aged 25 - 64 years . The joint estimates of intervention effect were in the expected direction in nine of 12 gender-specific comparisons ; however , these were not statistically significant . The results illustrate the analytic challenges of evaluating community-based prevention trials and point to the smaller than expected net differences , rather than small sample size , as the reason for few statistically significant effects in the three U.S. prevention trials", "The Minnesota Heart Health Program was a community trial of cardiovascular disease prevention methods that was conducted from 1980 to 1990 in three Upper Midwestern communities with three matched comparison communities . A 5- to 6-year intervention program used community-wide and individual health education in an attempt to decrease population risk . A major hypothesis was that the incidence of vali date d fatal and nonfatal coronary heart disease and stroke in 30- to 74-year-old men and women would decline differentially in the education communities after the health promotion program was introduced . This hypothesis was investigated using mixed-model regression . The intervention effect was modeled as a series of annual departures from a linear secular trend after a 2-year lag from the start of the intervention program . In the education communities , 2,394 cases of coronary heart disease and 818 cases of stroke occurred , with 2,526 and 739 cases , respectively , being seen in the comparison communities . The overall decline in coronary heart disease incidence was 1.8 percent per year in men ( p = 0.03 ) and 3.6 percent per year in women ( p = 0.007 ) . For stroke , there were no significant secular trends . The authors recently published findings showing minimal effects of sustained intervention on risk factor levels . In the current report , there was no evidence of a significant intervention effect on morbidity or mortality , either for coronary heart disease or for stroke", "Smokers ( N = 3,030 ) were r and omized to receive 1 of 3 interventions : ( a ) a self-help quit kit , ( b ) a quit kit plus 1 telephone counseling session , or ( c ) a quit kit plus up to 6 telephone counseling sessions , scheduled according to relapse probability . Both counseling groups achieved significantly higher abstinence rates than the self-help group . The rates for having quit for at least 12 months by intention to treat were 5.4 % for self-help , 7.5 % for single counseling , and 9.9 % for multiple counseling . The 12-month continuous abstinence rates for those who made a quit attempt were 14.7 % for self-help , 19.8 % for single counseling , and 26.7 % for multiple counseling . A dose-response relation was observed , as multiple sessions produced significantly higher abstinence rates than a single session . The first week after quitting seems to be the critical period for intervention", "Objectives : To investigate the importance of cost and awareness of health- or disease-promoting properties of foods and meals for choices by customers of a cafeteria . Design : A non-r and omized intervention study . Setting : A medium size cafeteria in the Harvard School of Public Health . Participants : Customers of the cafeteria mainly consisting of public health students , faculty , and school staff and workers from the medical campus . Intervention : The purchase of healthy foods and dishes was subsidized and their prices reduced by 20 % . This promotion was accompanied by the distribution of educational material . Main Outcome Measures : Change in consumption of healthy and less healthy foods . Analysis : The geometric mean was used to calculate the change in consumption . Results : During the intervention , we observed a 6 % increase in the consumption of healthy foods ( 95 % confidence interval [ CI ] ; 5 % to 8 % ) , and a 2 % decline in the consumption of less-healthy foods ( 95 % CI ; −1 % to −4 % ) . After the prices returned to their original levels , the consumption of healthy foods increased further to 17 % ( 95 % CI ; 13 % to 20 % ) and a 2 % decline in the consumption of less-healthy foods ( 95 % CI ; % 1 to −5 % ) persisted . Conclusions : Subsidizing healthful meals and educating consumers about the importance of a healthy diet can result in a modest increase in the selection of healthy foods and meals that can be maintained beyond the periods of subsidy and promotion", "OBJECTIVE To evaluate the effectiveness of computer-tailored newsletter interventions in improving the number and variety of fruits and vegetables eaten by adults . DESIGN The 4-group r and omized trial with pre- and postintervention measures consisted of a control group and 3 intervention groups receiving nontailored newsletters , computer-tailored newsletters , or tailored newsletters with tailored goal - setting information . Intervention groups received 1 newsletter each month for 4 months . SUBJECTS Baseline surveys were completed by 710 health maintenance organization clients . Postintervention surveys administered 6 months after baseline were completed by 573 participants ( 80.8 % ) . INTERVENTION All newsletters contained strategies for improving fruit and vegetable consumption . Tailored newsletters used computer algorithms to match a person 's baseline survey information with the most relevant newsletter messages for promoting dietary change . MAIN OUTCOME MEASURES Daily intake and weekly variety of fruits and vegetables were measured using a food frequency question naire . STATISTICAL ANALYSES PERFORMED Analysis of covariance and Tukey 's honestly significant difference test were used to assess differences in the number and variety of fruits and vegetables consumed among intervention groups . RESULTS For persons completing postintervention surveys ( n = 573 ) , all 3 newsletter groups had significantly higher daily intake and variety scores compared with the control group . Although there was a trend of improved intake and variety with each added newsletter element , there were no significant differences at follow-up among the newsletter groups . CONCLUSIONS Newsletters can be effective in improving the fruit and vegetable consumption of adults . In this study , a computer-tailoring system did not significantly enhance the effect of the nutrition newsletters on fruit and vegetable intake", "Purpose . Examine variation in obesity among older adults relative to the joint influences of density of neighborhood fast food outlets and residents ' behavioral , psychosocial , and sociodemographic characteristics . Design . Cross-sectional and multilevel design . Setting . Census block groups , used as a proxy for neighborhoods , within the metropolitan region 's Urban Growth Boundary in Portl and , Oregon . Subjects . A total of 1221 residents ( mean age , 65 years ) recruited r and omly from 120 neighborhoods ( 48 % response rate ) . Measures . A geographic information system-based measure of fast food restaurant density across 120 neighborhoods was created . Residents within the sample d neighborhoods were assessed with respect to their body mass indices ( BMI ) , frequency of visits to local fast food restaurants , fried food consumption , levels of physical activity , self-efficacy of eating fruits and vegetables , household income , and race/ethnicity . Analyses . Multilevel logistic regression analyses . Results . Significant associations were found between resident-level individual characteristics and the likelihood of being obese ( BMI ≥ 30 ) for neighborhoods with a high-density of fast food restaurants in comparison with those with a low density : odds ratios for obesity , 95 % confidence intervals ( CI ) , were 1.878 ( CI , 1.006–3.496 ) for weekly visits to local fast food restaurants ; 1.792 ( CI , 1.006–3.190 ) for not meeting physical activity recommendations ; 1.212 ( CI , 1.057–1.391 ) for low confidence in eating healthy food ; and 8.057 ( CI , 1.705–38.086 ) for non-Hispanic black residents . Conclusion . Increased density of neighborhood fast food outlets was associated with unhealthy lifestyles , poorer psychosocial profiles , and increased risk of obesity among older adults", "OBJECTIVE To examine the quantity ( density ) and location ( proximity ) of tobacco outlets and retail cigarette advertising in high school neighborhoods and their association with school smoking prevalence . METHODS Data from the 135 high schools that participated in the 2005 - 2006 California Student Tobacco Survey were combined with retailer licensing data about the location of tobacco outlets within walking distance ( 1/2 mi or 805 m ) of the schools and with observations about the quantity of cigarette advertising in a r and om sample of those stores ( n=384 ) . Multiple regressions , adjusting for school and neighborhood demographics , tested the associations of high school smoking prevalence with the density of tobacco outlets and retail cigarette advertising and with the proximity of tobacco outlets to schools . RESULTS The prevalence of current smoking was 3.2 percentage points higher at schools in neighborhoods with the highest tobacco outlet density ( > 5 outlets ) than in neighborhoods without any tobacco outlets . The density of retail cigarette advertising in school neighborhoods was similarly associated with high school smoking prevalence . However , neither the presence of a tobacco outlet within 1000 ft of a high school nor the distance to the nearest tobacco outlet from school was associated with smoking prevalence . CONCLUSIONS Policy efforts to reduce adolescent smoking should aim to reduce the density of tobacco outlets and retail cigarette advertising in school neighborhoods . This may be achieved through local zoning ordinances , including limiting the proximity of tobacco outlets to schools", "Abstract Objective : To determine the extent to which reducing the saturated fatty acid composition of a ubiquitously used cooking oil influenced changes in cholesterol concentration in the population during a five year intervention programme in Mauritius . Design : Cross sectional surveys in 1987 and 1992 determined mean total cholesterol concentrations in the population . A r and om sample of respondents in the 1992 survey completed a nutrition question naire that included questions on diet in the previous 24 hours . Setting : Mauritius . Intervention : In 1987 the government of Mauritius changed the composition of the commonly used cooking oil from being mostly palm oil ( high in saturated fatty acids ) to being wholly soya bean oil ( high in unsaturated fatty acids ) . Subjects : 5080 and 5162 subjects in 1987 and 1992 cross sectional surveys . 2059 subjects aged 30–64 years were r and omly selected from the respondents of the 1992 survey to take part in the nutrition survey Main outcome measures : Fatty acid composition of phospholipids in pooled serum sample s from men and women from the two surveys ; measured and predicted change in serum cholesterol concentration . Results : From 1987 to 1992 total cholesterol concentrations fell significantly by 0.79 mmol/l ( P intake of saturated fatty acids decreased by 3.5 % of energy intake in men and by 3.6 % in women , and the intake of polyunsaturated fatty acids increased by 5.5 % and 5.6 % of energy intake , respectively . These changes were reflected in changes in the fatty acid composition of serum phospholipids , and according to Keys ' formula these changes explained much of the decrease in serum cholesterol concentrations ( predicted decrease of 0.38 mmol/l in men and by 0.40 mmol/l in women ) . Conclusion : Dietary changes that entailed a reduction in the saturated fat content of a ubiquitous cooking oil explained most of the observed decrease in serum cholesterol concentration over five years in the population of Mauritius . Key messages The saturated fatty acid intake of Mauritians was reduced by modifying the composition of the widely used cooking oil Mean serum cholesterol concentration decreased by 15 % after the cooking oil intervention was introduced nationwide Effective , low cost prevention programmes for chronic disease are needed in less industrialised countries . Simple action in dietary policy could be one such", "OBJECTIVE Using a r and omised control trial design , this study assessed the impact of two walking interventions , on the work day step counts and health of UK academic and administrative , university employees . METHOD A convenience sample of 58 women ( age 42+/-10 years ) and 6 men ( age 40+/-11 years ) completed baseline and intervention measures for step counts , % body fat , waist circumference and systolic/diastolic blood pressure , during a ten-week period ( October to December , 2005 ) . Before intervention , baseline step counts ( five working days ) were used to r and omly allocate participants to a control ( maintain normal behaviour , n=22 ) and two treatment groups ( \" walking routes \" , n=21 ; \" walking in tasks \" , n=21 ) . Intervention effects were evaluated by calculating differences between pre-intervention and intervention data . A one-way ANOVA analysed significant differences between groups . RESULTS A significant intervention effect ( p step counts , with mean differences indicating a decrease in steps for the control group ( -767 steps/day ) and increases in the \" walking routes \" ( + 926 steps/day ) and \" walking in tasks \" ( + 997 steps/day ) groups . Small , non-significant changes were found in % body fat , waist circumference and blood pressure . CONCLUSIONS Findings have implication s for work-based physical activity promotion and the development of walking interventions within the completion of work-based tasks", "BACKGROUND Gender differences in smoking and smoking cessation among participants in the Working Well Trial are characterized . METHODS A prospect i ve r and omized matched-pair evaluation was conducted among 90 predominantly blue-collar worksites . Cross-sectional surveys of employees ' tobacco use behaviors were conducted at baseline and after a 2.5-year smoking cessation intervention . Respondents included 5,523 females and 12,313 males at baseline and 4,663 females and 10,919 males at follow-up . The main outcome measures included self-reported continuous smoking abstinence rates for 7 days and for 6 months . RESULTS Smoking prevalence was significantly higher for women than for men at baseline , but not at follow-up . Variables believed to influence smoking cessation were compared at baseline . Significant gender differences were found for number of cigarettes smoked/day , number of previous quit attempts , job strain , stage of change , and behavioral processes of change . At follow-up , no gender differences in quit rates were observed ; however , women in the intervention condition were more likely to quit than women in the control condition , whereas no differences were seen among men by treatment condition . CONCLUSIONS Gender is not a strong predictor of smoking cessation in this population ; however , women were more likely to quit with an intervention than without one", "BACKGROUND Childhood obesity has become a health problem in urban areas in China . Intervention to reduce childhood obesity should be of high priority . School-based intervention programmes are needed to deal with the growing prevalence of childhood obesity in China . METHODS Five primary schools were selected r and omly for this study in the Beijing urban area in China ; two were allocated to the intervention group and three to the control group . A total of 2425 children ( 1029 children in intervention schools and 1396 children in control schools ) took part in the study for 3 years . In the intervention group , children and their parents were involved in a programme of nutrition education and physical activity . Control school students followed their usual health and physical education curriculum with no extra intervention . RESULTS After the 3-year intervention , the prevalence of overweight and obesity were significantly lower in the intervention schools than in the control schools ( overweight : 9.8 % vs. 14.4 % , P prevalence of overweight and obesity decreased by 26.3 % and 32.5 % in intervention schools respectively after intervention . The prevalence of overweight and obesity increased in control schools . There was also significant difference in body mass index between intervention and control schools ( 18.2 + /- 2.6 vs. 20.3 + /- 3.4 , P non-obese children became obese in the control schools ( 7.0 % ) than in the intervention schools ( 2.4 % ) at end line ( P obese at end line in intervention schools while 61.9 % remained obese in control schools ( P schools in Beijing , China . The prevalence of overweight and obesity was reduced in schoolchildren in Beijing through an intervention focused on nutrition education and physical activity . Overweight and obesity children as well as normal weight children and their parents should be involved in such an intervention programme", "OBJECTIVES : To establish whether choice and availability of takeaway and restaurant food consumption are associated with increased obesity . DESIGN : Crossroads Undiagnosed Disease Study : a cross-sectional study undertaken between June 2001 and March 2003 . SETTING : A regional centre and six shire capitals of variables size in rural Victoria , Australia . PARTICIPANTS : In total , 1454 residents of r and omly selected households . MEASUREMENTS : Obesity ( by body mass index ( BMI ) or waist circumference ) , weekly recreational activity , self-reported frequency of takeaway consumption , number of local takeaway and restaurant food outlets in the area . RESULTS : The prevalence of obesity ranged from 25.5–30.8 % and was higher than the general Australian population among both men and women . Those in the regional centre were less likely than those in large and small shire capitals to participate in recreational activity of 150 min or more ( 39.7 vs 48.4 % , 46.0 % respectively , P=0.023 ) and yet reported better access to facilities and amenities for physical activity . Recreational activity of ≥150 min/week was associated with 0.75 ( 0.58–0.97 ) fold less risk of obesity . BMI was unrelated to takeaway consumption . Waist circumference was significantly lower among those eating no takeaways , but similar whether takeaways were consumed Increased takeaway consumption was associated with increased consumption of higher fat preparations of dairy and meat products . Availability of takeaway outlets and restaurants was unrelated to obesity . CONCLUSION : The obesity epidemic exists among those without significant consumption of or availability to takeaway foods . In a setting of easy availability of food , the obesity epidemic relates strongly to reduced physical activity , but not to consumption of takeaway food", "Modifying the food environment is a promising strategy for promoting healthier eating behavior . This study aim ed to evaluate nutritional and weight changes in a program that used worksite cafeterias to reduce employees ' calorie content of purchased foods and improve their macronutrient intake . Participants were r and omly assigned to one of two conditions : 1 ) only environmental change ( i.e. , the introduction of 10 new low-energy-density ( ED ) foods and provision of labels for all foods sold at lunch , which listed ED , calories , and macronutrient content ) or 2 ) the environmental change plus pricing incentives for purchasing low-ED foods and education about low-ED eating delivered in four , 1-hour group sessions . Participant lunch choices were monitored electronically at the point of purchase for 3 months before the intervention was instituted ( i.e. , the baseline period ) and for 3 months afterward ( i.e. , intervention period ) . Participants were adults ( n=96 , BMI = 29.7+/-6.0 kg/m(2 ) ) who regularly ate lunch at their workplace cafeteria . There was no difference between groups in total energy intake over the study period . Across groups , energy and percent of energy from fat decreased and percent of energy from carbohydrate increased from baseline to the intervention period ( all p energy , carbohydrate , and fat intake remained significant ( p nutrition labels and reducing the ED of selected foods was associated with improved dietary intake", "This study examined the impact of an environmental intervention in the form of promotional material s and increased availability of low-fat items on vending machine sales . Ten vending machines were selected and r and omly assigned to one of three conditions : control , or one of two experimental conditions . Vending machines in the two intervention conditions received three additional low-fat selection s. Low-fat items were promoted at two levels : labels ( intervention I ) , and labels plus signs ( intervention II ) . The number of individual items sold and the total revenue generated was recorded weekly for each machine for 4 weeks . Use of promotional material s result ed in a small , but not significant , increase in the number of low-fat items sold , although machine sales were not significantly impacted by the change in product selection . Results of this study , although not statistically significant , suggest that environmental change may be a realistic means of positively influencing consumer behavior", "OBJECTIVE The aim of this study was to examine the association between food prices and food outlet density and changes in the body mass index ( BMI ) among elementary school children in the USA . METHODS The Early Childhood Longitudinal Study followed a nationally representative sample of kindergarten children over 4 years . We merged individual-level data to ( a ) metropolitan data on food prices and ( b ) per capita number of restaurants , grocery stores and convenience stores in the child 's home and school zip code . The dependent variables were BMI changes over 1 and 3 years . We analysed mean changes with least-squares regression , and median changes and 85th percentile changes with quantile regression . We controlled for baseline BMI , age , real family income and sociodemographic characteristics . RESULTS Lower real prices for vegetables and fruits were found to predict a significantly lower gain in BMI between kindergarten and third grade ; half of that effect was found between kindergarten and first grade . Lower meat prices had the opposite effect , although this effect was generally smaller in magnitude and was insignificant for BMI gain over 3 years . Differences across subgroups were not statistically significant due to smaller sample sizes in subgroup analyses , but the estimated effects were meaningfully larger for children in poverty , children already at risk for overweight or overweight in kindergarten , and Asian and Hispanic children . There were no significant effects for dairy or fast-food prices , nor for outlet density , once we had controlled for individual characteristics and r and om intercepts to adjust st and ard errors for the sampling design . DISCUSSION The geographic variation in fruit and vegetable prices is large enough to explain a meaningful amount of the differential gain in BMI among elementary school children across metropolitan areas . However , as consumption information was not available , we can not confirm that this is the actual pathway . We found no effects of food outlet density at the neighbourhood level , possibly because availability is not an issue in metropolitan areas", "OBJECTIVES The purpose of this study was to evaluate the effect of a school-based intervention program to reduce overweight and improve fitness in primary school children . METHODS A cluster r and omized controlled design was used over one school year with schools as unit of r and omization . In total 20 schools and 2,622 children aged 6 - 12 years ( grade s 3 - 8 ) from multi-ethnic , low income inner-city neighbourhoods in Rotterdam , Netherl and s , participated . The intervention , named Lekker Fit ! ( Enjoy being fit ! ) was a multi-component intervention based on behavioural and ecological models . Main components of the intervention are the implementation of three physical education ( PE ) sessions a week by a professional PE teacher , additional sport and play activities outside school hours and an educational program . Main primary outcome measures were weight status , body mass index ( BMI ) , waist circumference and fitness ( 20 m shuttle run ) . RESULTS Significant positive intervention effects were found for percentage overweight children ( OR 0.53 ; 95 % CI 0.36 - 0.78 ) , waist circumference ( -1.29 cm ; 95 % CI -2.16 to -0.42 cm ) and 20 m shuttle run ( 0.57 laps ; 95 % CI 0.13 - 1.01 laps ) among pupils of grade s 3 - 5 ( 6 - 9-year olds ) . The prevalence of overweight in grade s 3 - 5 increased by 4.3 % in the control group and by 1.3 % in the intervention group . No significant effects were found for BMI or for grade s 6 - 8 ( 9 - 12-year olds ) . CONCLUSIONS Our results provide evidence for the effectiveness of the multi-component intervention Lekker Fit ! among pupils of grade s 3 - 5 and adds to the growing body of evidence that school-based programs with a focus on PA are most effective in reducing childhood obesity . [ IS RCT N84383524 ]", "OBJECTIVE The Nutrition Labeling and Education Act of 1990 m and ated that st and ardized nutrition information appear on almost all packaged foods manufactured after May 1994 . This study describes the demographic and diet-related psychosocial correlates of nutrition label use , and examines the relationship between label use and diet . DESIGN /SUBJECTS Data are from a r and om-digit-dial telephone survey of 1,450 adult residents of Washington State . The question naire assessed nutrition label use , fat-related diet habits , fruit and vegetable consumption , diet-related psychosocial factors , health behavior , and demographic characteristics . STATISTICAL ANALYSES Analyses examined associations of demographic characteristics with nutrition label use ; diet-related psychosocial factors and health behavior with nutrition label use , controlled for demographic characteristics ; and nutrition label use with fat and fruit and vegetable intake , controlled for demographic characteristics and psychosocial factors . RESULTS Nutrition label use was significantly higher among women , residents younger than 35 years , and residents with more than a high school education . When controlled for demographic characteristics , the strongest predictors of label use were believing in the importance of eating a low-fat diet , believing in an association between diet and cancer , and being in the maintenance stage of change for adopting a low-fat diet . Label use was significantly associated with lower fat intake and , after controlling for all demographic , psychosocial , and behavioral variables , explained 6 % of the variance in fat intake ( P fruit and vegetable consumption . APPLICATIONS/ CONCLUSION Persons successfully limiting their fat intake use nutrition labels , suggesting that the new nutrition labels are helpful . Dietetics professionals can use the results of this study to emphasize to their clients the importance of reading nutrition labels in maintaining a low-fat diet", "BACKGROUND Research has shown that lower socioeconomic groups purchase foods that are less consistent with dietary recommendations . The price and availability of foods are thought to be important mediating factors between socioeconomic position and food purchasing . OBJECTIVES We examined the relative contribution of the perceived and objective ly measured price and availability of recommended foods to household income differences in food purchasing . METHODS Using a face-to-face interview , a r and om sample of Brisbane residents ( n=812 ) were asked about their food purchasing choices in 2000 . They were also asked about their perceptions of the price and availability of ' recommended ' foods ( i.e. choices lower in fat , saturated fat , sugar , salt or higher in fibre ) in the supermarkets where they usually shopped . Audits measuring the actual availability and price of identical foods were conducted in the same supermarkets . RESULTS Lower socioeconomic groups were less likely to make food purchasing choices consistent with dietary guideline recommendations . Objective availability and price differences were not associated with purchasing choices , nor did they contribute to socioeconomic inequalities in food purchasing choices . Perceived availability and price differences were associated with the purchase of recommended foods . Perceived availability made a small contribution to inequalities in food purchasing , however perceived price differences did not . CONCLUSION Socioeconomic inequalities in food purchasing are not mediated by differential availability of recommended foods and differences in price between recommended and regular foods in supermarkets , or by perceptions of their relative price . However , differential perceptions of the availability of recommended foods may play a small role in food purchasing inequalities", "BACKGROUND A substantial challenge in addressing adolescent tobacco use is that smoking behaviors occur in complex environments that involve the school setting and larger community context . PURPOSE This study provides an integrated description of factors from the school and community environment that affect youth smoking and explains variation in individual smoking behaviors both within and across schools/communities . METHODS Data were collected from 82 r and omly sample d secondary schools in five Canadian provinces ( British Columbia , Manitoba , Ontario , Quebec , Newfoundl and , and Labrador ) during the 2003 - 2004 school year . Cross-sectional data were obtained from students ; school administrators ( school-based tobacco control policies and programs ) ; and from observations in the community . In 2009 , hierarchic logistic regression was used to model the role of individual , school , and community variables in predicting student smoking outcomes . RESULTS Students who attended a school with a focus on tobacco prevention ( OR=0.87 , 95 % CI=0.81 , 0.94 ) and stronger policies prohibiting tobacco use ( OR=0.92 , 95 % CI=0.88 , 0.97 ) were less likely to smoke than students who attended a school without these characteristics . A student was more likely to smoke if a greater number of students smoked on the school periphery ( OR=1.25 , 95 % CI=1.07 , 1.47 ) . Within the community , price per cigarette ( OR=0.91 , 95 % CI=0.84 , 0.99 ) and immigrants ( OR=0.99 , 95 % CI=0.98 , 0.99 ) were inversely related to students ' smoking status . CONCLUSIONS The results suggest that school and community characteristics account for variation in smoking levels across schools . Based on the current findings , the ideal school setting that supports low student smoking levels is located in a neighborhood where the cost of cigarettes is high , provides tobacco prevention education , and has a policy prohibiting smoking", "OBJECTIVE The authors evaluated the effectiveness of a community education campaign to encourage a switch from high-fat ( whole and 2 % ) milk to low-fat ( 1 % , 1/2 % , and skim ) milk as a way to reduce consumption of saturated fat . METHODS Milk sales data were collected from supermarkets in the intervention and comparison communities for three one-month time periods : at baseline , immediately following the campaign , and six months after the campaign . In addition , trained volunteers conducted pre- and post-intervention telephone surveys . RESULTS Overall milk sales increased by 16 % in the intervention cities following the campaign and remained high at follow-up . Low-fat milk 's market share increased from 18 % of overall milk sales at baseline to 41 % of overall milk sales in the month following the end of the campaign , an increase in market share that was sustained at the six-month follow-up . In the post-intervention telephone survey , 38.2 % of those respondents who reported drinking high-fat milk at baseline reported having switched to low-fat milk . CONCLUSION A focused message communicated through paid advertising , public relations activities , and community-based education programs increased low-fat and overall milk consumption in one community", "BACKGROUND Most public health studies on the neighborhood food environment have focused on types of stores and their geographic placement , yet marketing research has long documented the influence of in-store shelf-space on consumer behavior . PURPOSE This paper combines these two str and s of research to test whether the aggregate availability of specific foods in a neighborhood is associated with the BMI s of its residents . METHODS Fielded from October 2004 to August 2005 , this study combines mapping of retail food outlets , in-store surveys , and telephone interviews of residents from 103 r and omly sample d urban census tracts in southeastern Louisiana . Linear shelf-space of fruits , vegetables , and energy-dense snack foods was measured in 307 food stores in the study tracts . Residential addresses , demographic information , and heights and weights were obtained from 1243 respondents through telephone interviews . Cumulative shelf-space of foods within defined distances of each respondent was calculated using observations from the in-store survey and probability-based assignments of shelf-space to all unobserved stores in the area . RESULTS After controlling for sociodemographic variables , income , and car ownership , regression analysis , conducted in 2008 , showed that cumulative shelf-space availability of energy-dense snack foods was positively , although modestly , associated with BMI . A 100-meter increase in shelf-space of these foods within 1 kilometer of a respondent 's household was associated with an additional 0.1 BMI points . Fruit and vegetable shelf-space was not significantly related to BMI . CONCLUSIONS Interventions that seek to improve the neighborhood food environment may need to focus on more than just increasing access to healthy foods , because the results suggest that the availability of energy-dense snack foods plays a role in weight status", "OBJECTIVE Previous studies on the relationship of dietary intake to the neighbourhood food environment have focused on access to supermarkets , quantified by geographic distance or store concentration measures . However , in-store food availability may also be an important determinant , particularly for urban neighbourhoods with a greater concentration of small food stores . This study synthesis es both types of information - store access and in-store availability - to determine their potential relationship to fruit and vegetable consumption . DESIGN Residents in four census tracts were surveyed in 2001 about their fruit and vegetable intake . Household distances to food stores in these and surrounding tracts were obtained using geographical information system mapping techniques . In-store fruit and vegetable availability was measured by linear shelf space . Multivariate linear regression models were used to measure the association of these neighbourhood availability measures with consumption . SETTING Four contiguous census tracts in central -city New Orleans . SUBJECTS A r and om sample of 102 households . RESULTS Greater fresh vegetable availability within 100 m of a residence was a positive predictor of vegetable intake ; each additional metre of shelf space was associated with 0.35 servings per day of increased intake . Fresh fruit availability was not associated with intake , although having a small food store within this same distance was a marginal predictor of fruit consumption . CONCLUSIONS The findings suggest the possible importance of small neighbourhood food stores and their fresh produce availability in affecting fruit and vegetable intake", "Objective : To test the ability of two levels of modest financial incentives to encourage weight loss among overweight employees . Methods : This study used a r and omized design with measurements at baseline , 3 , and 6 months and two levels of financial incentives ( $ 7 and $ 14 per percentage point of weight lost ) . Payments were structured so that all participants had equal ability to obtain the incentives during the study period . Results : At 3 months , participants with no financial incentive lost 2 pounds , those in the $ 7 group lost approximately 3 pounds , and those in the $ 14 group lost 4.7 pounds . Between baseline and 6 months , when the financial gains were equalized , weight losses were similar across groups . Conclusion : This study revealed that modest financial incentives can be effective in motivating overweight employees to lose weight", "This article presents data from a population -based , r and om-digit dialing telephone survey of 1228 employed adults in Washington State , conducted 1989 through 1990 . Eighty-one percent of men and 91 % of women reported work-site smoking restrictions . Employees in work sites with no-smoking policies were less likely to be current smokers ; men in work sites with policies restricting smoking smoked fewer cigarettes on both workdays and nonworkdays . Forty-eight percent of male and 53 % of female smokers reported reduced smoking as a result of work-site policy . Work-site smoking policies , intended to protect against smoke exposure , may also reduce employee smoking", "OBJECTIVE To examine demographic and psychosocial factors that predict healthful dietary change . DESIGN A cohort study , examining how factors assessed at baseline predicted change in fat-related dietary habits and fruit and vegetable intakes 2 years later . PARTICIPANTS Participants were recruited in 1995 and 1996 by r and om-digit dialing ( response rate 0.63 ) , and followed-up in 1997 and 1998 ( follow-up rate 0.82 ) . The final sample included 336 men and 502 women . MAIN OUTCOME MEASURES Fruit and vegetable intake and fat-related dietary patterns , measured by telephone-administered surveys . STATISTICAL ANALYSES Chi2 tests and linear regression were used to test associations of baseline characteristics with dietary change . RESULTS Fat intake ( energy from fat ) decreased by approximately 2 percentage points and fruits and vegetables intake increased by 0.17 servings per day ( both P women and persons who were well educated . Persons in the maintenance stage of change and persons who believed there was a strong relationship between diet and cancer made the largest dietary changes . Use of food labels was strongly associated with fat reduction , but not with increases in fruits and vegetables . APPLICATIONS These results suggest that food labels are useful for helping people reduce fat intake , that interventions should target persons at all stages of dietary change , and that new efforts are needed to reach men and persons who are less well educated", "OBJECTIVE The role local neighbourhood environments play in influencing purpose -specific walking behaviors has not been well-explored in prospect i ve studies . This study aim ed to cross-sectionally and prospect ively examine whether local physical and social environments were associated with mothers ' walking for leisure and for transport . METHODS In 2004 , 357 mothers from Melbourne , Australia , provided information on their local physical and social neighbourhood environments , and in 2004 and 2006 reported weekly time spent walking for leisure and for transport . Environmental predictors of high levels of walking and increases in walking were examined using log binomial regression . RESULTS Public transport accessibility and trusting many people in the neighbourhood were predictive of increases in walking for leisure , while connectivity , pedestrian crossings , a local traffic speed were predictive of increases in transport-related walking . Satisfaction with local facilities was associated with increasing both types of walking , and the social environment was important for maintaining high levels of both leisure- and transport-related walking . CONCLUSION The findings provide evidence of a longitudinal relationship between physical and social environments and walking behaviors amongst mothers . Enhancing satisfaction with local facilities and giving consideration to ' walkability ' , safety and public transport accessibility during environment planning processes may help mothers to increase walking", "Although blood cholesterol levels in the United States have decreased slightly since the late 1980s ( 1 ) , consumption of saturated and trans fats remains above recommended maximum levels ( 2 , 3 ) , and only one quarter of U.S. adults with high cholesterol have it under control ( 4 ) . Some 24 million U.S. adults report taking cholesterol-lowering medications ( 5 ) . Changing a person 's nutrition-related behavior to improve cholesterol control is challenging ( 6 ) and a source of frustration for clinicians ( 7 ) . Public health action can complement health care provider efforts . The New York City Department of Health and Mental Hygiene adopted such a strategy when it restricted the use of artificial trans fat in restaurant food . We describe the rationale and process that led to this New York City Health Code amendment and the Department 's experience implementing the rule . Artificial trans fat is an unnecessary ingredient that poses a substantial risk to heart health . Although no r and omized , controlled trials have assessed the effect of trans fat consumption on cardiovascular events , evidence from experimental studies , dietary trials , and prospect i ve observational studies ( 3 , 8) demonstrates that consumption of trans fatty acids provides no apparent nutritional benefit and has considerable potential for harm . The Institute of Medicine ( 3 ) concluded that a positive linear trend exists between trans fatty acid intake and low-density lipoprotein cholesterol level , which increases the risk for coronary heart disease . Unlike saturated fat , trans fat also decreases high-density lipoprotein cholesterol levels ( 3 , 8 , 9 ) . Trans fat intake has a large effect on cardiovascular health : A mere 2 % increase in energy intake from trans fat may increase the risk for a coronary event by up to 23 % ( 8) . Other potential adverse effects have been noted , such as affecting insulin sensitivity and increasing systemic inflammation , which raises additional public health concerns ( 8 , 10 ) . Each year , 6 % to 19 % of coronary heart disease events and 30000 or more premature deaths are estimated to occur in the United States because of trans fat consumption ( 8 , 11 ) . The Institute of Medicine , the American Heart Association , the U.S. Department of Agriculture , and other leading health organizations recommend minimizing trans fat intake ( 3 , 1215 ) . To achieve this , health care providers are asked to counsel patients ( 12 ) . However , such advice is unlikely to be broadly effectivemillions of Americans would need to routinely study package labels on groceries and actively seek information on trans fat in restaurant foods , where a growing proportion of calories are now consumed . Health would be better served by making the use of safer fats the default in food preparation . The Emergence of Artificial Trans Fat and Recognition of Its Risks Trans fats occur naturally in small amounts in some meat and dairy products ( 3 ) ; however , these sources make up only 21 % of total trans fat intake ( 16 ) . The remaining trans fat in the U.S. diet is artificial , produced by partial hydrogenation of vegetable oils and found mostly in processed foodsespecially baked and fried goods and spreads . Partial hydrogenation was patented in 1903 . Eight years later , Crisco ( J.M. Smucker , Orrville , Ohio ) became the first such product widely marketed in the United States ( 17 ) . These chemically modified oils , like several food ingredients in the 20th century , entered the food supply without a full evaluation of human health effects and were generally recognized as safe on the basis of experience ( 18 ) . Industrial advantages , such as extended product shelf life and fry oil stability , led to increased use in the 1950s . In the 1970s , margarine made from partially hydrogenated oil was promoted as a healthier alternative to butter ( 19 ) . However , by the 1990s , studies began to identify trans fat as a health hazard ( 9 ) . In 2003 , the U.S. Food and Drug Administration ( FDA ) required that all packaged goods display information on trans fat content by 2006 ( 20 ) . The regulation allows products that contain less than 0.5 grams of trans fat per serving to be labeled zero grams trans fat . This prompted a widespread industry response of reformulating products to declare zero grams trans fat on front-of-package labeling ( 2123 ) , although such products may still contain trans fat in small amounts , which can add up . The nutrition facts labeling allowed attentive consumers to avoid trans fat in packaged foods ; however , restaurantswhich provide one third of daily caloric intake (24)generally do not disclose nutritional information , leaving consumers no practical way to avoid trans fat . At the time of the FDA action , only Denmark limited trans fat in its entire food supply ( 25 ) . Although local health departments do not commonly regulate packaged goods , inspecting , licensing , and regulating restaurants and retail food outlets are core local public health functions ( 26 ) . Building on its food safety infrastructure , the Department trained restaurant inspectors in May 2005 to assess the presence of artificial trans fat in products used for frying , baking , or cooking or in spreads by means of food label inspection . Because inspection visits are scheduled each year on the basis of original restaurant licensing date and compliance records , a survey fielded during regularly scheduled inspections approximates a r and om sample of these establishments . In May and June 2005 , inspectors assessed the use of trans fat in oils , shortenings , and spreads used for frying , baking , or cooking or in spreads in 529 restaurants . Of the 478 restaurants that used fats for any of these purpose s and for which complete data were collected , trans fat presence could not be determined in one third . Where it could be assessed , 50 % of restaurants used artificial trans fat to prepare food . Educational Campaign In August 2005 , the Department launched an educational campaign to reduce restaurant artificial trans fat use . Information was sent to the 30000 licensed food outlets in the city , 15000 suppliers and supermarkets , and hundreds of thous and s of consumers . Mailings urged restaurants to remove artificial trans fat from food , suppliers to promote 0-grams trans fat products , and patrons to inquire about oils used . Press coverage was extensive ( 2729 ) . More than 7800 restaurant operators received training on the issue during the m and atory food protection course . Nearly a year later , inspectors surveyed 1021 restaurants in April and May 2006 by following the same methodology as the previous year . Despite the educational campaign , prevalence of artificial trans fat use remained virtually unchanged at 51 % in places where it could be assessed . Given survey findings of a wide range of restaurants that cooked without artificial trans fat , successful reformulation of packaged foods , and the Danish experience , the Department concluded that food choice and quality would be unaffected by replacing artificial trans fat and proposed using its regulatory authority to reduce artificial trans fat use ( 26 ) . Crafting Regulation Department clinical staff , food safety experts , and lawyers considered a range of regulatory options , from disclosure-only requirements to content restrictions . Labeling trans fat would benefit only consumers who were aware of and would act on the dangers of trans fat and would be difficult to enforce . A restriction , however , would benefit all New Yorkers , regardless of language , literacy , level of health awareness , or age . Protecting children , who consume French fries and other quick-service foods that are common sources of artificial trans fat ( 30 ) , was particularly important . Because artificial trans fat is both harmful and fully replaceable , allowing continued use , even with disclosure , could not be justified . Similarly , restricting trans fat in cooking oils and spreads onlyalthough easier to achievewould be insufficient because baked goods are the largest dietary source of trans fat ( 16 ) . Given that an estimated one third of calories comes from away-from-home sources , removing most trans fat from restaurants could be expected to reduce trans fatassociated deaths proportionately . The Department drafted a broad proposal to restrict artificial trans fat use in fry oils ; spreads ; and all other ingredients and products , including baked goods . For the regulation to be clear and enforceable , the Department adopted the FDA threshold used for labeling of up to 0.5 grams of trans fat per serving for products containing any trans fat ( 20 ) . The regulation would apply to all licensed food establishments , including restaurants , school cafeterias , caterers , senior centers , and street-food vendors . It intentionally did not affect products that contained only natural trans fat . The Department design ed enforcement to rely on existing infrastructure . Inspectors check product labels , which restaurants now must maintain , during their regular annual inspections . The rule included a 6-month phase-out period for artificial trans fat in fry oils and spreads and 18 months for all other items , to give restaurants time to identify alternatives and reformulate ( 31 ) . Fines for violations range from $ 200 to $ 2000 . From Concept to Action The regulation was proposed as an amendment to the city 's Health Code , approvable by the Board of Health . Nearly 2300 public comments were received , with supporters outnumbering opponents 31 to 1 . Local , regional , and national organizations and professional medical associations made statements of support . Opposition came primarily from industry associations , including the National Restaurant Association and its state affiliate and the Grocery Manufacturers Association ( 32 ) . The restaurant industry , which often opposes regulation on principle , alleged that the elimination of artificial trans fat would result in more expensive and less flavorful food and also cl aim ed that the supply of alternative oils was insufficient and the regulatory timeline", "BACKGROUND Empiric studies find that context ual factors affect individual weight status over and above individual socioeconomic characteristics . Given increasing levels of obesity , research ers are examining how the food environment contributes to unhealthy weight status . An important change to this environment is the increasing availability of away-from-home eating establishments such as restaurants . METHODS This study analyzed the relationship between the restaurant environment and weight status across counties in the United States . Individual data from the 2002 - 2006 Behavioral Risk Factor Surveillance System ( N=714,054 ) were linked with restaurant data from the 2002 U.S. Economic Census . Fast-food and full-service restaurant density , along with restaurant mix ( the ratio of fast-food to full-service restaurants ) , were assessed . RESULTS Fast-food restaurant density and a higher ratio of fast-food to full-service restaurants were associated with higher individual-level weight status ( BMI and the risk of being obese ) . In contrast , a higher density of full-service restaurants was associated with lower weight status . CONCLUSIONS Area-level restaurant mix emerged as an important correlate of weight status , with components of the restaurant environment exhibiting differential associations . Hence , it is the availability of fast-food relative to other away-from-home choices that appears salient for unhealthy weight outcomes . Areas with a high density of full-service restaurants were indicative of a more healthful eating environment , suggesting a need for research into the comparative healthfulness of foods served at different types of restaurants . Future prospect i ve studies are required to delineate causal pathways", "Anti-smoking media directed at adolescents use many different message themes , but little evidence exists as to which is most effective . Additionally , little is known about how teens who smoke respond to anti-tobacco ads . This study examined smoking and nonsmoking adolescents ' responses to three popular thematic approaches : ( 1 ) endangering others , ( 2 ) negative life circumstances , and ( 3 ) industry manipulation . Sixteen groups of high school students ( total N = 488 ) were r and omly assigned in a balanced fashion to one of three anti-tobacco ad conditions or a control condition . Outcome variables included adolescents ' immediate emotional and cognitive responses , and intentions to smoke . Adolescents exposed to negative life circumstances ads reported lower intentions to smoke than those exposed to control and industry manipulation ads . Additionally , adolescents ' responses differed based on smoking status . Smokers liked the ads less and had fewer positive and more negative thoughts . Findings suggest a media campaign focusing on negative life circumstances can be an effective component of a tobacco control program aim ed at adolescents . Mechanisms through which the negative life circumstances ads influence adolescents ' intentions to smoke are discussed . Findings also suggest that smokers respond differently to anti-tobacco ads , and their responses need to be considered when developing effective anti-tobacco advertising campaigns" ]	4118929e-06ff-11f0-808a-c43d1ab1c353
Added sugars are a controversial and hotly debated topic . Consumption of added sugars has been implicated in increased risk of a variety of chronic diseases including obesity , cardiovascular disease , diabetes and non-alcoholic fatty liver disease ( NAFLD ) as well as cognitive decline and even some cancers . Support for these putative associations has been challenged , however , on a variety of fronts . The purpose of the current review is to summarize high impact evidence including systematic review s , meta-analyses , and r and omized controlled trials ( RCTs ) , in an attempt to provide an overview of current evidence related to added sugars and health considerations . This paper is an extension of a symposium held at the Experimental Biology 2015 conference entitled " Sweeteners and Health : Current Underst and ings , Controversies , Recent Research Findings and Directions for Future Research " . We conclude based on high quality evidence from r and omized controlled trials ( RCT ) , systematic review s and meta-analyses of cohort studies that singling out added sugars as unique culprits for metabolically based diseases such as obesity , diabetes and cardiovascular disease appears inconsistent with modern , high quality evidence and is very unlikely to yield health benefits . While it is prudent to consume added sugars in moderation , the reduction of these components of the diet without other reductions of caloric sources seems unlikely to achieve any meaningful benefit	[ "OBJECTIVE Adverse effects of hypercaloric , high-fructose diets on insulin sensitivity and lipids in human subjects have been shown repeatedly . The implication s of fructose in amounts close to usual daily consumption , however , have not been well studied . This study assessed the effect of moderate amounts of fructose and sucrose compared with glucose on glucose and lipid metabolism . RESEARCH DESIGN AND METHODS Nine healthy , normal-weight male volunteers ( aged 21–25 years ) were studied in this double-blind , r and omized , cross-over trial . All subjects consumed four different sweetened beverages ( 600 mL/day ) for 3 weeks each : medium fructose ( MF ) at 40 g/day , and high fructose ( HF ) , high glucose ( HG ) , and high sucrose ( HS ) each at 80 g/day . Euglycemic-hyperinsulinemic clamps with [6,6]-2H2 glucose labeling were used to measure endogenous glucose production . Lipid profile , glucose , and insulin were measured in fasting sample s. RESULTS Hepatic suppression of glucose production during the clamp was significantly lower after HF ( 59.4 ± 11.0 % ) than HG ( 70.3 ± 10.5 % , P whereas fasting glucose , insulin , and C-peptide did not differ between the interventions . Compared with HG , LDL cholesterol and total cholesterol were significantly higher after MF , HF , and HS , and free fatty acids were significantly increased after MF , but not after the two other interventions ( P 0.05 ) . Subjects ’ energy intake during the interventions did not differ significantly from baseline intake . CONCLUSIONS This study clearly shows that moderate amounts of fructose and sucrose significantly alter hepatic insulin sensitivity and lipid metabolism compared with similar amounts of glucose", "OBJECTIVE To examine associations between type 2 diabetes and fiber , glycemic load ( GL ) , dietary glycemic index ( GI ) , and fiber-rich foods . RESEARCH DESIGN AND METHODS This was a prospect i ve study of 36,787 men and women aged 40 - 69 years without diabetes . For all self-reported cases of diabetes at 4-year follow-up , confirmation of diagnosis was sought from medical practitioners . Case subjects were those who reported diabetes at follow-up and for whom there was no evidence that they did not have type 2 diabetes . Data were analyzed with logistic regression , adjusting for country of birth , physical activity , family history of diabetes , alcohol and energy intake , education , 5-year weight change , sex , and age . RESULTS Follow-up was completed by 31,641 ( 86 % ) participants , and 365 cases were identified . The odds ratio ( OR ) for the highest quartile of white bread intake compared with the lowest was 1.37 ( 95 % CI 1.04 - 1.81 ; P for trend = 0.001 ) . Intakes of carbohydrate ( OR per 200 g/day 0.58 , 0.36 - 0.95 ) , sugars ( OR per 100 g/day 0.61 , 0.47 - 0.79 ) , and magnesium ( OR per 500 mg/day 0.62 , 0.43 - 0.90 ) were inversely associated with incidence of diabetes , whereas intake of starch ( OR per 100 g/day 1.47 , 1.06 - 2.05 ) and dietary GI ( OR per 10 units 1.32 , 1.05 - 1.66 ) were positively associated with diabetes . These relationships were attenuated after adjustment for BMI and waist-to-hip ratio . CONCLUSIONS Reducing dietary GI while maintaining a high carbohydrate intake may reduce the risk of type 2 diabetes . One way to achieve this would be to substitute white bread with low-GI breads", "BACKGROUND Because egg yolk has a high cholesterol concentration , limited egg consumption is often suggested to help prevent ischemic heart disease ( IHD ) . OBJECTIVE We epidemiologically examined the validity of this recommendation . DESIGN We analyzed the relations of egg consumption to serum cholesterol and cause-specific and all-cause mortality by using the NIPPON DATA 80 ( National Integrated Project for Prospect i ve Observation of Non-communicable Disease And its Trends in the Aged , 1980 ) data base . At the baseline examination in 1980 , a nutritional survey was performed by using the food-frequency method in Japanese subjects aged > or = 30 y. We followed 5186 women and 4077 men for 14 y. RESULTS The subjects were categorized into 5 egg consumption groups on the basis of their responses to a question naire ( > or = 2/d , 1/d , 1/2 d , 1 - 2/wk , and seldom ) . There were 69 , 1396 , 1667 , 1742 , and 315 women in each of the 5 groups , respectively . Age-adjusted total cholesterol ( 5.21 , 5.04 , 4.95 , 4.91 , and 4.92 mmol/L in the 5 egg consumption categories , respectively ) was related to egg consumption ( P unadjusted IHD mortality and all-cause mortality differed significantly between the groups [ IHD mortality : 1.1 , 0.5 , 0.4 , 0.5 , and 2.0 per 1000 person-years , respectively ( P = 0.008 , chi-square test ) ; all-cause mortality : 14.8 , 8.0 , 7.5 , 7.5 , and 14.5 per 1000 person-years , respectively ( P egg consumption was not related to age-adjusted total cholesterol . Cox analysis found that , in women , all-cause mortality in the 1 - 2-eggs/wk group was significantly lower than that in the 1-egg/d group , whereas no such relations were noted in men . CONCLUSION Limiting egg consumption may have some health benefits , at least in women in geographic areas where egg consumption makes a relatively large contribution to total dietary cholesterol intake", "BACKGROUND Dietary carbohydrates may influence the development of type 2 ( non-insulin-dependent ) diabetes , for example , through effects on blood glucose and insulin concentrations . OBJECTIVE We examined the relations of baseline intake of carbohydrates , dietary fiber , dietary magnesium , and carbohydrate-rich foods and the glycemic index with incidence of diabetes . DESIGN This was a prospect i ve cohort study of 35988 older Iowa women initially free of diabetes . During 6 y of follow-up , 1141 incident cases of diabetes were reported . RESULTS Total grain , whole-grain , total dietary fiber , cereal fiber , and dietary magnesium intakes showed strong inverse associations with incidence of diabetes after adjustment for potential nondietary confounding variables . Multivariate-adjusted relative risks of diabetes were 1.0 , 0.99 , 0.98 , 0.92 , and 0.79 ( P for trend : 0.0089 ) across quintiles of whole-grain intake ; 1.0 , 1.09 , 1.00 , 0.94 , and 0.78 ( P for trend : 0.005 ) across quintiles of total dietary fiber intake ; and 1.0 , 0.81 , 0.82 , 0.81 , and 0.67 ( P for trend : 0.0003 ) across quintiles of dietary magnesium intake . Intakes of total carbohydrates , refined grains , fruit and vegetables , and soluble fiber and the glycemic index were unrelated to diabetes risk . CONCLUSION These data support a protective role for grains ( particularly whole grains ) , cereal fiber , and dietary magnesium in the development of diabetes in older women", "To determine the relations of diet with risk of clinical noninsulin-dependent diabetes , we analyzed data from a prospect i ve cohort of 84360 US women . During 6 y of follow-up we identified 702 definite incident cases . Because body mass index ( BMI ) is a powerful risk factor for diabetes , we examined the relations of fat ( including type ) , fiber , sucrose , and other components of diet to risk of diabetes , among women with BMI s ( in kg/m2 ) less than 29 kg/m2 . After controlling for body mass index , previous weight change , and alcohol intake , we observed no associations between intakes of energy , protein , sucrose , carbohydrate , or fiber and risk of diabetes . Compared with women in the lowest quintile of energy-adjusted intake , and relative risks ( and tests for trend ) for those in the highest quintile were 0.61 ( P trend = 0.03 ) for vegetable fat , 0.62 ( P trend = 0.008 ) for potassium , 0.70 ( P trend = 0.005 ) for calcium , and 0.68 ( P trend = 0.02 ) for magnesium . These inverse associations were attenuated among obese women ( BMI s greater than or equal to 29 )", "BACKGROUND The consumption of sucrose-sweetened soft drinks ( SSSDs ) has been associated with obesity , the metabolic syndrome , and cardiovascular disorders in observational and short-term intervention studies . Too few long-term intervention studies in humans have examined the effects of soft drinks . OBJECTIVE We compared the effects of SSSDs with those of isocaloric milk and a noncaloric soft drink on changes in total fat mass and ectopic fat deposition ( in liver and muscle tissue ) . DESIGN Overweight subjects ( n = 47 ) were r and omly assigned to 4 different test drinks ( 1 L/d for 6 mo ) : SSSD ( regular cola ) , isocaloric semiskim milk , aspartame-sweetened diet cola , and water . The amount of intrahepatic fat and intramyocellular fat was measured with (1)H-magnetic resonance spectroscopy . Other endpoints were fat mass , fat distribution ( dual-energy X-ray absorptiometry and magnetic resonance imaging ) , and metabolic risk factors . RESULTS The relative changes between baseline and the end of 6-mo intervention were significantly higher in the regular cola group than in the 3 other groups for liver fat ( 132 - 143 % , sex-adjusted mean ; P skeletal muscle fat ( 117 - 221 % ; P visceral fat ( 24 - 31 % ; P blood triglycerides ( 32 % ; P total cholesterol ( 11 % ; P Total fat mass was not significantly different between the 4 beverage groups . Milk and diet cola reduced systolic blood pressure by 10 - 15 % compared with regular cola ( P diet cola had effects similar to those of water . CONCLUSION Daily intake of SSSDs for 6 mo increases ectopic fat accumulation and lipids compared with milk , diet cola , and water . Thus , daily intake of SSSDs is likely to enhance the risk of cardiovascular and metabolic diseases . This trial is registered at clinical trials.gov as NCT00777647", "IMPORTANCE Epidemiologic studies have suggested that higher intake of added sugar is associated with cardiovascular disease ( CVD ) risk factors . Few prospect i ve studies have examined the association of added sugar intake with CVD mortality . OBJECTIVE To examine time trends of added sugar consumption as percentage of daily calories in the United States and investigate the association of this consumption with CVD mortality . DESIGN , SETTING , AND PARTICIPANTS National Health and Nutrition Examination Survey ( NHANES , 1988 - 1994 [ III ] , 1999 - 2004 , and 2005 - 2010 [ n = 31,147 ] ) for the time trend analysis and NHANES III Linked Mortality cohort ( 1988 - 2006 [ n = 11 733 ] ) , a prospect i ve cohort of a nationally representative sample of US adults for the association study . MAIN OUTCOMES AND MEASURES Cardiovascular disease mortality . RESULTS Among US adults , the adjusted mean percentage of daily calories from added sugar increased from 15.7 % ( 95 % CI , 15.0%-16.4 % ) in 1988 - 1994 to 16.8 % ( 16.0%-17.7 % ; P = .02 ) in 1999 - 2004 and decreased to 14.9 % ( 14.2%-15.5 % ; P added sugar ( 71.4 % ) and approximately 10 % consumed 25 % or more in 2005 - 2010 . During a median follow-up period of 14.6 years , we documented 831 CVD deaths during 163,039 person-years . Age- , sex- , and race/ethnicity-adjusted hazard ratios ( HRs ) of CVD mortality across quintiles of the percentage of daily calories consumed from added sugar were 1.00 ( reference ) , 1.09 ( 95 % CI , 1.05 - 1.13 ) , 1.23 ( 1.12 - 1.34 ) , 1.49 ( 1.24 - 1.78 ) , and 2.43 ( 1.63 - 3.62 ; P added sugar with those who consumed less than 10.0 % of calories from added sugar . These findings were largely consistent across age group , sex , race/ethnicity ( except among non-Hispanic blacks ) , educational attainment , physical activity , health eating index , and body mass index . CONCLUSIONS AND RELEVANCE Most US adults consume more added sugar than is recommended for a healthy diet . We observed a significant relationship between added sugar consumption and increased risk for CVD mortality", "Background / Objectives : The results of short-term studies in humans suggest that , compared with glucose , acute consumption of fructose leads to increased postpr and ial energy expenditure and carbohydrate oxidation and decreased postpr and ial fat oxidation . The objective of this study was to determine the potential effects of increased fructose consumption compared with isocaloric glucose consumption on substrate utilization and energy expenditure following sustained consumption and under energy-balanced conditions . Subjects/ Methods : As part of a parallel arm study , overweight/obese male and female subjects , 40–72 years , consumed glucose- or fructose-sweetened beverages providing 25 % of energy requirements for 10 weeks . Energy expenditure and substrate utilization were assessed using indirect calorimetry at baseline and during the 10th week of intervention . Results : Consumption of fructose , but not glucose , led to significant decreases of net postpr and ial fat oxidation and significant increases of net postpr and ial carbohydrate oxidation ( P . Resting energy expenditure ( REE ) decreased significantly from baseline values in subjects consuming fructose ( P=0.031 ) but not in those consuming glucose . Conclusions : Increased consumption of fructose for 10 weeks leads to marked changes of postpr and ial substrate utilization including a significant reduction of net fat oxidation . In addition , we report that REE is reduced compared with baseline values in subjects consuming fructose-sweetened beverages for 10 weeks", "OBJECTIVE In normal adults , a small ( catalytic ) dose of fructose administered with glucose decreases the glycemic response to a glucose load , especially in those with the poorest glucose tolerance . We hypothesized that an acute catalytic dose of fructose would also improve glucose tolerance in individuals with type 2 diabetes . RESEARCH DESIGN AND METHODS Five adults with type 2 diabetes underwent an oral glucose tolerance test ( OGTT ) on two separate occasions , at least 1 week apart . Each OGTT consisted of 75 g glucose with or without the addition of 7.5 g fructose ( OGTT + F or OGTT - F ) , in r and om order . Arterialized blood sample s were collected from a heated dorsal h and vein twice before ingestion of the carbohydrate and every 15 min for 3 h afterward . RESULTS The area under the curve ( AUC ) of the plasma glucose response was reduced by fructose administration in all subjects ; the mean AUC during the OGTT + F was 14 % less than that during the OGTT - F ( P insulin AUC was decreased 21 % with fructose administration ( P = 0.2 ) . Plasma glucagon concentrations declined similarly during OGTT - F and OGTT + F. The incremental AUC of the blood lactate response during the OGTT - F was approximately 50 % of that observed during the OGTT + F ( P nonesterified fatty acid nor triglyceride concentrations differed between the two OGTTs . CONCLUSIONS Low-dose fructose improves the glycemic response to an oral glucose load in adults with type 2 diabetes , and this effect is not a result of stimulation of insulin secretion", "Consumption of sugar-sweetened beverages has been shown , largely in American population s , to increase type 2 diabetes incidence . We aim ed to evaluate the association of consumption of sweet beverages ( juices and nectars , sugar-sweetened soft drinks and artificially sweetened soft drinks ) with type 2 diabetes incidence in European adults . We established a case – cohort study including 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants selected from eight European cohorts participating in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study . After exclusions , the final sample size included 11,684 incident cases and a subcohort of 15,374 participants . Cox proportional hazards regression models ( modified for the case – cohort design ) and r and om-effects meta-analyses were used to estimate the association between sweet beverage consumption ( obtained from vali date d dietary question naires ) and type 2 diabetes incidence . In adjusted models , one 336 g ( 12 oz ) daily increment in sugar-sweetened and artificially sweetened soft drink consumption was associated with HRs for type 2 diabetes of 1.22 ( 95 % CI 1.09 , 1.38 ) and 1.52 ( 95 % CI 1.26 , 1.83 ) , respectively . After further adjustment for energy intake and BMI , the association of sugar-sweetened soft drinks with type 2 diabetes persisted ( HR 1.18 , 95 % CI 1.06 , 1.32 ) , but the association of artificially sweetened soft drinks became statistically not significant ( HR 1.11 , 95 % CI 0.95 , 1.31 ) . Juice and nectar consumption was not associated with type 2 diabetes incidence . This study corroborates the association between increased incidence of type 2 diabetes and high consumption of sugar-sweetened soft drinks in European adults", "OBJECTIVE To investigate the long-term effects of changes in dietary carbohydrate/fat ratio and simple vs complex carbohydrates . DESIGN R and omized controlled multicentre trial ( CARMEN ) , in which subjects were allocated for 6 months either to a seasonal control group ( no intervention ) or to one of three experimental groups : a control diet group ( dietary intervention typical of the average national intake ) ; a low-fat high simple carbohydrate group ; or a low-fat high complex carbohydrate group . SUBJECTS Three hundred and ninety eight moderately obese adults . MEASUREMENTS The change in body weight was the primary outcome ; changes in body composition and blood lipids were secondary outcomes . RESULTS Body weight loss in the low-fat high simple carbohydrate and low-fat high complex carbohydrate groups was 0.9 kg ( P control diet and seasonal control groups gained weight ( 0.8 and 0.1 kg , NS ) . Fat mass changed by -1.3 kg ( P Changes in blood lipids did not differ significantly between the dietary treatment groups . CONCLUSION Our findings suggest that reduction of fat intake results in a modest but significant reduction in body weight and body fatness . The concomitant increase in either simple or complex carbohydrates did not indicate significant differences in weight change . No adverse effects on blood lipids were observed . These findings underline the importance of this dietary change and its potential impact on the public health implication s of obesity", "OBJECTIVE To investigate prospect ively whether intake of total or type of sugar is associated with the risk of developing type 2 diabetes . The contribution of sugar intake to the pathogenesis of type 2 diabetes has not been settled in the context of primary prevention because of limited prospect i ve data . RESEARCH DESIGN AND METHODS The Women 's Health Study is a r and omized controlled trial of aspirin and vitamin E in the prevention of cardiovascular disease and cancer . A vali date d semiquantitative food frequency question naire was completed by 39,345 women aged 45 years and older . The main outcome was the incidence of type 2 diabetes . The predictor was sugar intake , including sucrose , glucose , fructose , and lactose . Using Cox proportional hazard models , multivariate RRs of type 2 diabetes for increasing quintiles of sugar intake compared with the lowest quintile were estimated . RESULTS Compared with the lowest quintile of sugar intake , the RRs and 95 % CIs for the highest quintiles were 0.84 ( 0.67 - 1.04 ) for sucrose , 0.96 ( 0.78 - 1.19 ) for fructose , 1.04 ( 0.85 - 1.28 ) for glucose , and 0.99 ( 0.80 - 1.22 ) for lactose , after adjustment for known risk factors for type 2 diabetes . Similar findings of no association were obtained in subgroup analyses stratified by BMI . CONCLUSIONS Intake of sugars does not appear to play a deleterious role in primary prevention of type 2 diabetes . These prospect i ve data support the recent American Diabetes Association 's guideline that a moderate amount of sugar can be incorporated in a healthy diet", "The American Heart Association ( AHA ) has advocated that women and men not consume more than 100 and 150 kcal/day , respectively , from added sugars . These levels are currently exceeded by over 90 % of the adult population in the United States . Few data exist on longer-term metabolic effects when sucrose and High Fructose Corn Syrup ( HFCS ) , the principal sources of added dietary sugars , are consumed at levels typical of the general population . Sixty five overweight and obese individuals were placed on a eucaloric ( weight stable ) diet for 10-weeks , which incorporated sucrose- or HFCS-sweetened , low-fat milk at 10 % or 20 % of calories in a r and omized , double-blinded study . All groups responded similarly ( interaction p > 0.05 ) . There was no change in body weight in any of the groups over the 10-week study , or in systolic or diastolic blood pressure . Likewise , there were no changes in total cholesterol , triglycerides , low-density lipoprotein ( LDL ) , or apolipoprotein B ( Apo B ) . We conclude that ( 1 ) when consumed as part of a eucaloric diet fructose — when given with glucose ( as normally consumed ) does not promote weight gain or an atherogenic lipid profile even when consumed at two to four times the level recently recommended by the AHA . ( 2 ) There were no differences between HFCS and sucrose on these parameters", "Background The replacement of sucrose with HFCS in food products has been suggested as playing a role in the development of obesity as a public health issue . The objective of this study was to examine the effects of four equally hypocaloric diets containing different levels of sucrose or high fructose corn syrup ( HFCS ) . Methods This was a r and omized , prospect i ve , double blind trial , with overweight/obese participants measured for body composition and blood chemistry before and after the completion of 12 weeks following a hypocaloric diet . The average caloric deficit achieved on the hypocaloric diets was 309 kcal . Results Reductions were observed in all measures of adiposity including body mass , BMI , % body fat , waist circumference and fat mass for all four hypocaloric groups , as well as reductions in the exercise only group for body mass , BMI and waist circumference . Conclusions Similar decreases in weight and indices of adiposity are observed when overweight or obese individuals are fed hypocaloric diets containing levels of sucrose or high fructose corn syrup typically consumed by adults in the United States", "OBJECTIVE Many guidelines recommend reduced consumption of salt in patients with type 1 diabetes , but it is unclear whether dietary sodium intake is associated with mortality and end-stage renal disease ( ESRD ) . RESEARCH DESIGN AND METHODS In a nationwide multicenter study ( the FinnDiane Study ) between 1998 and 2002 , 2,807 enrolled adults with type 1 diabetes without ESRD were prospect ively followed . Baseline urinary sodium excretion was estimated on a 24-h urine collection . The predictors of all-cause mortality and ESRD were determined by Cox regression and competing risk modeling , respectively . RESULTS The median follow-up for survival analyses was 10 years , during which 217 deaths were recorded ( 7.7 % ) . Urinary sodium excretion was nonlinearly associated with all-cause mortality , such that individuals with the highest daily urinary sodium excretion , as well as the lowest excretion , had reduced survival . This association was independent age , sex , duration of diabetes , the presence and severity of chronic kidney disease ( CKD ) ( estimated glomerular filtration rate [ eGFR ] and log albumin excretion rate ) , the presence of established cardiovascular disease , and systolic blood pressure . During follow-up , 126 patients developed ESRD ( 4.5 % ) . Urinary sodium excretion was inversely associated with the cumulative incidence of ESRD , such that individuals with the lowest sodium excretion had the highest cumulative incidence of ESRD . CONCLUSIONS In patients with type 1 diabetes , sodium was independently associated with all-cause mortality and ESRD . Although we have not demonstrated causality , these findings support the calls for caution before applying salt restriction universally . Clinical trials must be performed in diabetic patients to formally test the utility/risk of sodium restriction in this setting", "The long-term impact of dietary carbohydrate type , in particular sucrose , on insulin resistance and the development of diabetes and atherosclerosis is not established . Current guidelines for the healthy population advise restriction of sucrose intake . We investigated the effect of high- versus low-sucrose diet ( 25 vs. 10 % , respectively , of total energy intake ) in 13 healthy subjects aged 33 ± 3 years ( mean ± SE ) , BMI 26.6 ± 0.9 kg/m2 , in a r and omized crossover design with sequential 6-week dietary interventions separated by a 4-week washout . Weight maintenance , eucaloric diets with identical macronutrient profiles and fiber content were design ed . All food was weighed and distributed . Insulin action was assessed using a two-step euglycemic clamp ; glycemic profiles were assessed by the continuous glucose monitoring system and vascular compliance by pulse-wave analysis . There was no change in weight across the study . Peripheral glucose uptake and suppression of endogenous glucose production were similar after each diet . Glycemic profiles and measures of vascular compliance did not change . A rise in total and LDL cholesterol was observed . In this study , a high-sucrose intake as part of an eucaloric , weight-maintaining diet had no detrimental effect on insulin sensitivity , glycemic profiles , or measures of vascular compliance in healthy nondiabetic subjects", "CONTEXT Consumption of high-fructose diets promotes hepatic fatty acid synthesis ( de novo lipogenesis [ DNL ] ) and an atherogenic lipid profile . It is unclear whether these effects occur independent of positive energy balance and weight gain . OBJECTIVES We compared the effects of a high-fructose , ( 25 % of energy content ) weight-maintaining diet to those of an isocaloric diet with the same macronutrient distribution but in which complex carbohydrate ( CCHO ) was substituted for fructose . DESIGN , SETTING , AND PARTICIPANTS Eight healthy men were studied as in patients for consecutive 9-day periods . Stable isotope tracers were used to measure fractional hepatic DNL and endogenous glucose production ( EGP ) and its suppression during a euglycemic-hyperinsulinemic clamp . Liver fat was measured by magnetic resonance spectroscopy . RESULTS Weight remained stable . Regardless of the order in which the diets were fed , the high-fructose diet was associated with both higher DNL ( average , 18.6 ± 1.4 % vs 11.0 ± 1.4 % for CCHO ; P = .001 ) and higher liver fat ( median , + 137 % of CCHO ; P = .016 ) in all participants . Fasting EGP and insulin-mediated glucose disposal did not differ significantly , but EGP during hyperinsulinemia was greater ( 0.60 ± 0.07 vs 0.46 ± 0.06 mg/kg/min ; P = .013 ) with the high-fructose diet , suggesting blunted suppression of EGP . CONCLUSION Short-term high-fructose intake was associated with increased DNL and liver fat in healthy men fed weight-maintaining diets", "People are advised to reduce their intake of saturated fat and replace it by carbohydrate to avoid coronary heart disease . It is unknown whether sucrose and starchy foods , two major sources of carbohydrates , have similar effects on cardiovascular risk markers if incorporated as a replacement for saturated fat into diets eaten ad libitum . We served 20 healthy , normal-weight women aged 21 to 52 years three strictly controlled diets ad libitum : FAT , high in total fat ( 46 % of total energy [ E% ] ) and saturated fat ( 21 E% ) ; STARCH , high in total carbohydrates ( 59 E% ) and low in sucrose ( 2.5 E% ) ; and SUCROSE , high in total carbohydrates ( 59 E% ) and sucrose ( 23.2 E% ) . The diets were eaten in r and omized order for a period of 2 weeks . Blood lipids , factor VII coagulant activity ( FVIIc ) , and fibrinogen concentrations were measured with subjects in the fasted state ( 9:45 AM ) and the postabsorptive state ( 6:00 PM ) . STARCH was associated with lower total cholesterol ( mean difference , 0.34 mmol/L ; 95 % confidence interval [ CI ] , 0.18 to 0.50 ) , low-density lipoprotein ( LDL ) cholesterol ( 0.25 mmol/L ; 95 % CI , 0.13 to 0.37 ) , fasting triglycerides ( 0.15 mmol/L ; 95 % CI , 0.07 to 0.23 ) , nonfasting triglycerides ( 0.44 mmol/L ; 95 % CI , 0.30 to 0.58 ) , and nonfasting FVIIc ( 9.8 % ; 95 % CI , 3.8 to 15.8 ) than SUCROSE . Compared with FAT , STARCH result ed in a desirable decrease of LDL cholesterol and nonfasting FVIIc . STARCH was also associated with a minor weight loss ( 0.7 kg ) that was not found on the other 2 diets . We conclude that starchy foods with a natural content of dietary fiber can be recommended as substitutes for saturated fat in the dietary prevention of coronary heart disease . According to the present short-term findings in healthy females , substitution with sucrose is not advisable", "BACKGROUND Although dietary recommendations have focused on restricting saturated fat ( SF ) consumption to reduce cardiovascular disease ( CVD ) risk , evidence from prospect i ve studies has not supported a strong link between total SF intake and CVD events . An underst and ing of whether food sources of SF influence these relations may provide new insights . OBJECTIVE We investigated the association of SF consumption from different food sources and the incidence of CVD events in a multiethnic population . DESIGN Participants who were 45 - 84 y old at baseline ( n = 5209 ) were followed from 2000 to 2010 . Diet was assessed by using a 120-item food-frequency question naire . CVD incidence ( 316 cases ) was assessed during follow-up visits . RESULTS After adjustment for demographics , lifestyle , and dietary confounders , a higher intake of dairy SF was associated with lower CVD risk [ HR ( 95 % CI ) for + 5 g/d and + 5 % of energy from dairy SF : 0.79 ( 0.68 , 0.92 ) and 0.62 ( 0.47 , 0.82 ) , respectively ] . In contrast , a higher intake of meat SF was associated with greater CVD risk [ HR ( 95 % CI ) for + 5 g/d and a + 5 % of energy from meat SF : 1.26 ( 1.02 , 1.54 ) and 1.48 ( 0.98 , 2.23 ) , respectively ] . The substitution of 2 % of energy from meat SF with energy from dairy SF was associated with a 25 % lower CVD risk [ HR ( 95 % CI ) : 0.75 ( 0.63 , 0.91 ) ] . No associations were observed between plant or butter SF and CVD risk , but ranges of intakes were narrow . CONCLUSION Associations of SF with health may depend on food-specific fatty acids or other nutrient constituents in foods that contain SF , in addition to SF", "BACKGROUND National Health and Nutrition Examination Survey data show an increased risk of cardiovascular disease ( CVD ) mortality with an increased intake of added sugar . OBJECTIVE We determined the dose-response effects of consuming beverages sweetened with high-fructose corn syrup ( HFCS ) at zero , low , medium , and high proportions of energy requirements ( Ereq ) on circulating lipid/lipoprotein risk factors for CVD and uric acid in adults [ age : 18 - 40 y ; body mass index ( in kg/m(2 ) ) : 18 - 35 ] . DESIGN We conducted a parallel-arm , nonr and omized , double-blinded intervention study in which adults participated in 3.5 inpatient days of baseline testing at the University of California Davis Clinical and Translational Science Center 's Clinical Research Center . Participants then consumed beverages sweetened with HFCS at 0 % ( aspartame sweetened , n = 23 ) , 10 % ( n = 18 ) , 17.5 % ( n = 16 ) , or 25 % ( n = 28 ) of Ereq during 13 outpatient days and during 3.5 inpatient days of intervention testing at the research center . We conducted 24-h serial blood collection s during the baseline and intervention testing periods . RESULTS Consuming beverages containing 10 % , 17.5 % , or 25 % Ereq from HFCS produced significant linear dose-response increases of lipid/lipoprotein risk factors for CVD and uric acid : postpr and ial triglyceride ( 0 % : 0 ± 4 ; 10 % : 22 ± 8 ; 17.5 % : 25 ± 5 : 25 % : 37 ± 5 mg/dL , mean of Δ ± SE , P effect of HFCS-dose ) , fasting LDL cholesterol ( 0 % : -1.0 ± 3.1 ; 10 % : 7.4 ± 3.2 ; 17.5 % : 8.2 ± 3.1 ; 25 % : 15.9 ± 3.1 mg/dL , P ( 0 % : -0.13 ± 0.07 ; 10 % : 0.15 ± 0.06 ; 17.5 % : 0.30 ± 0.07 ; 25 % : 0.59 ± 0.09 mg/dL , P 0.0001 ) . Compared with beverages containing 0 % HFCS , all 3 doses of HFCS-containing beverages increased concentrations of postpr and ial triglyceride , and the 2 higher doses increased fasting and /or postpr and ial concentrations of non-HDL cholesterol , LDL cholesterol , apolipoprotein B , apolipoprotein CIII , and uric acid . CONCLUSIONS Consuming beverages containing 10 % , 17.5 % , or 25 % Ereq from HFCS produced dose-dependent increases in circulating lipid/lipoprotein risk factors for CVD and uric acid within 2 wk . These results provide mechanistic support for the epidemiologic evidence that the risk of cardiovascular mortality is positively associated with consumption of increasing amounts of added sugars . This trial was registered at clinical trials.gov as NCT01103921", "AIMS In animals , intracerebroventricular glucose and fructose have opposing effects on appetite and weight regulation . In humans , functional brain magnetic resonance imaging ( fMRI ) studies during glucose ingestion or infusion have demonstrated suppression of hypothalamic signalling , but no studies have compared the effects of glucose and fructose . We therefore sought to determine if the brain response differed to glucose vs. fructose in humans independently of the ingestive process . METHODS Nine healthy , normal weight subjects underwent blood oxygenation level dependent ( BOLD ) fMRI measurements during either intravenous ( IV ) glucose ( 0.3 mg/kg ) , fructose ( 0.3 mg/kg ) or saline , administered over 2 min in a r and omized , double-blind , crossover study . Blood was sample d every 5 min during a baseline period and following infusion for 60 min in total for glucose , fructose , lactate and insulin levels . RESULTS No significant brain BOLD signal changes were detected in response to IV saline . BOLD signal in the cortical control areas increased during glucose infusion ( p = 0.002 ) , corresponding with increased plasma glucose and insulin levels . In contrast , BOLD signal decreased in the cortical control areas during fructose infusion ( p = 0.006 ) , corresponding with increases of plasma fructose and lactate . Neither glucose nor fructose infusions significantly altered BOLD signal in the hypothalamus . CONCLUSION In normal weight humans , cortical responses as assessed by BOLD fMRI to infused glucose are opposite to those of fructose . Differential brain responses to these sugars and their metabolites may provide insight into the neurologic basis for dysregulation of food intake during high dietary fructose intake" ]	411892da-06ff-11f0-808a-c43d1ab1c353
Probiotics have been suggested to play an important role in the management of diabetes . We conducted a systematic review on the role of probiotics in modulating parameters related to diabetes in animal and human experiments . We search ed Pubmed , Scopus and Cochrane central until June 2014 , concerning the effects of probiotics on hyperglycemia , hyperinsulinemia and their anti-diabetic efficacies by modulating the activities of proinflammatory and antioxidant factors . Our initial search retrieved 1120 reports . After screening titles and abstract s , 72 full-text articles were review ed for eligibility . Ultimately , 33 articles met our inclusion criteria consisting of five human and twenty eight animal reports . Lactobacillus strains were , in particular , used in all studies with or without other strains . We found that probiotics have beneficial effects on glycemic controls , as all human studies showed significant reductions in at least one of the primary outcome endpoints which were the levels of fasting plasma glucose , postpr and ial blood glucose , glycated haemoglobin , insulin , insulin resistance and onset of diabetes ; similarly , all the animal reports , except for two , documented significant changes in these parameters . Regarding secondary outcome measures , that is , lipid profiles , pro-inflammatory and anti-oxidant factors , only one human and one animal study failed to show any significant changes in any of these parameters . This systematic review generally demonstrated beneficial effects of the probiotic administration , especially Lactobacillus sub-strains , on the management of diabetes-related blood parameters , although , more evidence , especially from human trials , is needed to confirm these effects and also to conduct a meta- analysis . Copyright © 2015 John Wiley & Sons ,	[ "Epidemiological studies have shown an inverse association between dietary intake of whole grains and the risk of chronic disease . This may be related to the ability to mediate a prebiotic modulation of gut microbiota . However , no studies have been conducted on the microbiota modulatory capability of whole-grain ( WG ) cereals . In the present study , the impact of WG wheat on the human intestinal microbiota compared to wheat bran ( WB ) was determined . A double-blind , r and omised , crossover study was carried out in thirty-one volunteers who were r and omised into two groups and consumed daily 48 g breakfast cereals , either WG or WB , in two 3-week study periods , separated by a 2-week washout period . Numbers of faecal bifidobacteria and lactobacilli ( the target genera for prebiotic intake ) , were significantly higher upon WG ingestion compared with WB . Ingestion of both breakfast cereals result ed in a significant increase in ferulic acid concentrations in blood but no discernible difference in faeces or urine . No significant differences in faecal SCFA , fasting blood glucose , insulin , total cholesterol ( TC ) , TAG or HDL-cholesterol were observed upon ingestion of WG compared with WB . However , a significant reduction in TC was observed in volunteers in the top quartile of TC concentrations upon ingestion of either cereal . No adverse intestinal symptoms were reported and WB ingestion increased stool frequency . Daily consumption of WG wheat exerted a pronounced prebiotic effect on the human gut microbiota composition . This prebiotic activity may contribute towards the beneficial physiological effects of WG wheat", "Background : The dramatic increase in the incidence of diabetes and its associated complications require a natural and safe solution to control and delay such complications . The present study tested the hypothesis that probiotics may affect biochemical indices of diabetic patients Methods : Thirty four types 2 diabetic patients aged between 25 to 65 years , and diagnosed with diabetes for less than 15 years were selected for this single- blinded clinical trial . Using balanced block r and om sampling , the patients were divided into two groups of intervention ( probiotics ) and placebo . Blood sample s tested for baseline glucose , insulin , TG , total cholesterol , LDL-C , HDL-C , malondialdehyde , high sensitive CRP ( hs-CRP ) and IL-6 . After six weeks of experiment , fasting blood sample s were re-tested and the data obtained were analyzed using SPSS software . Results : There were no significant differences between anthropometric data including body mass index and waist to hip ratio in placebo and treatment groups . There was no significant difference in FBS , Serum TG concentration total cholesterol and LDL-C levels between placebo and treatment groups . HDL-C levels were slightly elevated after probiotic treatment , which were not statistically significant . Insulin , MDA and IL-6 levels were reduced and high sensitive CRP hs . CRP levels were elevated , although , not statistically significant . Conclusion : The result of this study indicates a non- significant declining trend in the level of TG , MDA and IL-6 and insulin resistance after consumption of probiotics", "According to animal studies , intake of probiotic bacteria may improve glucose homeostasis . We hypothesised that probiotic bacteria improve insulin sensitivity by attenuating systemic inflammation . Therefore , the effects of oral supplementation with the probiotic bacterium Lactobacillus acidophilus NCFM on insulin sensitivity and the inflammatory response were investigated in subjects with normal or impaired insulin sensitivity . In a double-blinded , r and omised fashion , forty-five males with type 2 diabetes , impaired or normal glucose tolerance were enrolled and allocated to a 4-week treatment course with either L. acidophilus NCFM or placebo . L. acidophilus was detected in stool sample s by denaturating gradient gel electrophoresis and real-time PCR . Separated by the 4-week intervention period , two hyperinsulinaemic-euglycaemic clamps were performed to estimate insulin sensitivity . Furthermore , the systemic inflammatory response was evaluated by subjecting the participants to Escherichia coli lipopolysaccharide injection ( 0·3 ng/kg ) before and after the treatment course . L. acidophilus NCFM was detected in 75 % of the faecal sample s after treatment with the probiotic bacterium . Insulin sensitivity was preserved among volunteers in the L. acidophilus NCFM group , whereas it decreased in the placebo group . Both baseline inflammatory markers and the systemic inflammatory response were , however , unaffected by the intervention . In conclusion , intake of L. acidophilus NCFM for 4 weeks preserved insulin sensitivity compared with placebo , but did not affect the systemic inflammatory response ", "OBJECTIVE —Vitamin K has a potentially beneficial role in insulin resistance , but evidence is limited in humans . We tested the hypothesis that vitamin K supplementation for 36 months will improve insulin resistance in older men and women . RESEARCH DESIGN AND METHODS —This was an ancillary study of a 36-month , r and omized , double-blind , controlled trial design ed to assess the impact of supplementation with 500 μg/day phylloquinone on bone loss . Study participants were older nondiabetic men and women ( n = 355 ; aged 60–80 years ; 60 % women ) . The primary outcome of this study was insulin resistance as measured by homeostasis model assessment ( HOMA-IR ) at 36 months . Fasting plasma insulin and glucose were examined as the secondary outcomes . RESULTS —The effect of 36-month vitamin K supplementation on HOMA-IR differed by sex ( sex × treatment interaction P = 0.02 ) . HOMA-IR was statistically significantly lower at the 36-month visit among men in the supplement group versus the men in the control group ( P = 0.01 ) after adjustment for baseline HOMA-IR , BMI , and body weight change . There were no statistically significant differences in outcome measures between intervention groups in women . CONCLUSIONS —Vitamin K supplementation for 36 months at doses attainable in the diet may reduce progression of insulin resistance in older men", "Background The consumption of foods containing probiotic and prebiotic ingredients is growing consistently every year , and in view of the limited number of studies investigating their effect in the elderly . Objective The objective of this study was to evaluate the effect of the consumption of a symbiotic shake containing Lactobacillus acidophilus , Bifidobacterium bifidum and fructooligosaccharides on glycemia and cholesterol levels in elderly people . Methods A r and omized , double-blind , placebo-controlled study was conducted on twenty volunteers ( ten for placebo group and ten for symbiotic group ) , aged 50 to 60 years . The criteria for inclusion in the study were : total cholesterol > 200 mg/dL ; triglycerides > 200 mg/dL and glycemia > 110 mg/dL. Over a total test period of 30 days , 10 individuals ( the symbiotic group ) consumed a daily dose of 200 mL of a symbiotic shake containing 108 UFC/mL Lactobacillus acidophilus , 108 UFC/mL Bifidobacterium bifidum and 2 g oligofructose , while 10 other volunteers ( the placebo group ) drank daily the same amount of a shake that did not contain any symbiotic bacteria . Blood sample s were collected 15 days prior to the start of the experiment and at 10-day intervals after the beginning of the shake intake . The st and ard lipid profile ( total cholesterol , triglycerides and HDL cholesterol ) and glycemia , or blood sugar levels , were evaluated by an enzyme colorimetric assay . Results The results of the symbiotic group showed a non-significant reduction ( P > 0.05 ) in total cholesterol and triglycerides , a significant increase ( P HDL cholesterol and a significant reduction ( P fasting glycemia . No significant changes were observed in the placebo group . Conclusion The consumption of symbiotic shake result ed in a significant increase in HDL and a significant decrease of glycemia . Trial Registration Clinical Trials.gov :", "Introduction : The role of inflammatory cytokines in diabetes and its complications has been shown in some studies . The purpose of this study was to compare the effect of probiotic and conventional yogurt on inflammatory markers in patients with type 2 diabetes . Methods : Forty-four patients with type 2 diabetes were participated in this r and omized , double-blind controlled clinical trial and assigned to two intervention and control groups . The subjects in the intervention group consumed 300 g/d probiotic yogurt and subjects in the control group consumed 300 g/d conventional yogurt for 8 weeks . Anthropometric indices , dietary intakes , and serum levels of glucose , HbA1c , IL-6 , TNF-α and hs-CRP were evaluated at the beginning and end of the intervention . Results : For anthropometric indices and dietary intakes , no significant differences were seen within and between groups post intervention ( p > 0.05 ) . The consumption of probiotic yogurt caused significant decrease in HbA1c and TNF-α levels ( p= 0.032 and p= 0.040 , respectively ) in the intervention group . Conclusion : It is suggested that probiotic yogurt may be used as an alternative prevention approach and treatment method to control diabetic complications ", "Background Obesity is increasing in the child-bearing population as are the rates of gestational diabetes . Gestational diabetes is associated with higher rates of Cesarean Section for the mother and increased risks of macrosomia , higher body fat mass , respiratory distress and hypoglycemia for the infant . Prevention of gestational diabetes through life style intervention has proven to be difficult . A Finnish study showed that ingestion of specific probiotics altered the composition of the gut microbiome and thereby metabolism from early gestation and decreased rates of gestational diabetes in normal weight women . In SPRING ( the Study of Probiotics IN the prevention of Gestational diabetes ) , the effectiveness of probiotics ingestion for the prevention of gestational diabetes will be assessed in overweight and obese women . Methods / design SPRING is a multi-center , prospect i ve , double-blind r and omized controlled trial run at two tertiary maternity hospitals in Brisbane , Australia . Five hundred and forty ( 540 ) women with a BMI > 25.0 kg/m2 will be recruited over 2 years and receive either probiotics or placebo capsules from 16 weeks gestation until delivery . The probiotics capsules contain > 1x109 cfu each of Lactobacillus rhamnosus GG and Bifidobacterium lactis BB-12 per capsule . The primary outcome is diagnosis of gestational diabetes at 28 weeks gestation . Secondary outcomes include rates of other pregnancy complications , gestational weight gain , mode of delivery , change in gut microbiome , preterm birth , macrosomia , and infant body composition . The trial has 80 % power at a 5 % 2-sided significance level to detect a > 50 % change in the rates of gestational diabetes in this high-risk group of pregnant women . Discussion SPRING will show if probiotics can be used as an easily implementable method of preventing gestational diabetes in the high-risk group of overweight and obese pregnant women", "The perinatal nutritional environment impacts upon the health and well-being of mother and child also in the long term . The aim of the present study was to determine the safety and efficacy of perinatal probiotic-supplemented dietary counselling by evaluating pregnancy outcome and fetal and infant growth during the 24 months ' follow-up . Altogether , 256 women were r and omised at their first trimester of pregnancy into a control and a dietary intervention group . The intervention group received intensive dietary counselling provided by a nutritionist and were further r and omised , double-blind to receive probiotics ( Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 ; diet/probiotics ) or placebo ( diet/placebo ) . Firstly , probiotic intervention reduced the frequency of gestational diabetes mellitus ( GDM ) ; 13 % ( diet/probiotics ) v. 36 % ( diet/placebo ) and 34 % ( control ) ; P = 0.003 . Secondly , the safety of this approach was attested by normal duration of pregnancies with no adverse events in mothers or children . No significant differences in prenatal or postnatal growth rates among the study groups were detected . Thirdly , distinctive effects of the two interventions were detected ; probiotic intervention reduced the risk of GDM and dietary intervention diminished the risk of larger birth size in affected cases ; P = 0.035 for birth weight and P = 0.028 for birth length . The results of the present study show that probiotic-supplemented perinatal dietary counselling could be a safe and cost-effective tool in addressing the metabolic epidemic . In view of the fact that birth size is a risk marker for later obesity , the present results are of significance for public health in demonstrating that this risk is modifiable", "Background / objectives : Owing to excess body weight and increased secretion of inflammatory cytokines primarily during the third trimester , pregnancy is associated with elevated insulin resistance . To our knowledge , no report is available indicating the effects of probiotic yoghurt consumption on serum insulin levels in pregnant women . This study was design ed to determine the effects of daily consumption of probiotic yoghurt on insulin resistance and serum insulin levels of Iranian pregnant women . Subjects/ methods : In this r and omized controlled clinical trial , 70 primigravida pregnant women with singleton pregnancy at their third trimester were participated . We r and omly assigned participants to consume 200 g per day of conventional ( n=33 ) or the probiotic group ( n=37 ) for 9 weeks . The probiotic yoghurt was a commercially available product prepared with the starter cultures of Streptococcus thermophilus and Lactobacillus bulgaricus , enriched with probiotic culture of two strains of lactobacilli ( Lactobacillus acidophilus LA5 ) and bifidobacteria ( Bifidobacterium animalis BB12 ) with a total of min 1 × 107 colony-forming units . Fasting blood sample s were taken at baseline and after 9-week intervention to measure fasting plasma glucose and serum insulin levels . Homeostatic model assessment of insulin resistance ( HOMA-IR ) was used to calculate insulin resistance score . Results : Although consumption of probiotic yogurt for 9 weeks did not affect serum insulin levels and HOMA-IR score , significant differences were found comparing changes in these variables between probiotic and conventional yogurts ( changes from baseline in serum insulin levels : + 1.2±1.2 vs + 5.0±1.1 μIU/ml , respectively , P=0.02 ; and in HOMA-IR score : −0.2±0.3 vs 0.7±0.2 , respectively , P=0.01 ) . Conclusions : It is concluded that in contrast to conventional yogurt , daily consumption of probiotic yogurt for 9 weeks maintains serum insulin levels and might help pregnant women prevent developing insulin resistance", "OBJECTIVE Oxidative stress plays a major role in the pathogenesis and progression of diabetes . Among various functional foods with an antioxidant effect , probiotic foods have been reported to repress oxidative stress . The objective of this clinical trial was to assess the effects of probiotic and conventional yogurt on blood glucose and antioxidant status in type 2 diabetic patients . METHODS Sixty-four patients with type 2 diabetes mellitus , 30 to 60 y old , were assigned to two groups in this r and omized , double-blind , controlled clinical trial . The patients in the intervention group consumed 300 g/d of probiotic yogurt containing Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 and those in the control group consumed 300 g/d of conventional yogurt for 6 wk . Fasting blood sample s , 24-h dietary recalls , and anthropometric measurements were collected at the baseline and at the end of the trial . RESULTS Probiotic yogurt significantly decreased fasting blood glucose ( P hemoglobin A1c ( P erythrocyte superoxide dismutase and glutathione peroxidase activities and total antioxidant status ( P serum malondialdehyde concentration significantly decreased compared with the baseline value in both groups ( P insulin concentration and erythrocyte catalase activity within either group ( P > 0.05 ) . CONCLUSION The consumption of probiotic yogurt improved fasting blood glucose and antioxidant status in type 2 diabetic patients . These results suggest that probiotic yogurt is a promising agent for diabetes management", "We examined 72 patients with T2D and NAFLD . All patients divided by us on the way of therapy into 2 groups . The main group ( n = 45 ) received oral antidiabetic therapy and multiprobiotic \" Symbiter \" within 30 days . Patients of comparison group ( n = 27 ) received only hypoglycemic drugs . Also in each group we identified patients with normal and elevated level of transaminases . We observed 1.5 - 2 times increasing of cytokines in patients with NAFLD and elevated transaminase levels compared to patients with normal transaminase levels . We noted statistically significant reduction of proinflammatory cytokines in plasma , after 30 days of therapy , in patients with elevated levels of transaminases . In particular , the level of IL-6 decreased on 30.9 % ( P IL-8 - 19.9 % ( P = 0.001 ) , TNF-alpha - 13.4 % ( P IL-1beta - 17.9 % ( P IFN-gamma on 18.7 % ( P levels transaminases and NAFLD were significantly decreased only TNF-alpha on 15.1 % ( P = 0.003 ) and IL-8 on 15.2 % ( P = 0.017 ) . Significant changes in cytokines levels in patients of comparative group we do n't observed . Probiotics can be recommended for use in patients with different stages of NAFLD and T2D as an adjunct to st and ard treatment regimens because it decreases manifestations of low- grade systemic inflammatory response", "A naturally occurring gastrointestinal disease , primarily of ruminants ( Johne disease ) , is a chronic debilitating disease that is caused by Mycobacterium avium subspecies paratuberculosis ( MAP ) . MAP infection occurs primarily in utero and in newborns . Outside our Dietzia probiotic treatment , there are no preventive/curative therapies for bovine paratuberculosis . Interestingly , MAP is at the center of controversy as to its role in ( cause of ) Crohn disease ( CD ) and more recently , its role in diabetes , ulcerative colitis , and irritable bowel syndrome ( IBS ) ; the latter two , like CD , are considered to be a result of chronic intestinal inflammation . Treatments , both conventional and biologic agents , which induce and maintain remission are directed at curtailing processes that are an intricate part of inflammation . Most possess side effects of varying severity , lose therapeutic value , and more importantly , none routinely result in prevention and /or cures . Based on ( a ) similarities of Johne disease and Crohn disease , ( b ) a report that Dietzia inhibited growth of MAP under specific culture conditions , and ( c ) findings that Dietzia when used as a probiotic , ( i ) was therapeutic for adult bovine paratuberculosis , and ( ii ) prevented development of disease in MAP-infected calves , the goal of the present investigations was to design protocol s that have applicability for IBD patients . Dietzia was found safe for cattle of all ages and for normal and immunodeficient mice . The results strongly warrant clinical evaluation as a probiotic , in combination with/without dexamethasone", "Sourdough bread has been reported to improve glucose metabolism in healthy subjects . In this study postpr and ial glycaemic and insulinaemic responses were evaluated in subjects with impaired glucose tolerance ( IGT ) who had a meal containing sourdough bread leavened with lactobacilli , in comparison to a reference meal containing bread leavened with baker yeast . Sixteen IGT subjects ( age range 52–75 , average BMI 29.9 ± 4.2 kg/m² ) were r and omly given a meal containing sourdough bread ( A ) and a meal containing the reference bread ( B ) in two separate occasions at the beginning of the study and after 7 days . Sourdough bread was leavened for 8 h using a starter containing autochthonous Saccharomyces cerevisiae and several bacilli able to produce a significant amount of d- and l-lactic acid , whereas the reference bread was leavened for 2 h with commercial baker yeast containing Saccharomyces cerevisiae . Plasma glucose and insulin levels were measured at time 0 , 30 , 60 , 120 , and 180 min . In IGT subjects sourdough bread induced a significantly lower plasma glucose response at 30 minutes ( p = 0.048 ) and a smaller incremental area under curve ( AUC ) Δ 0–30 and Δ 0–60 min ( p = 0.020 and 0.018 respectively ) in comparison to the bread leavened with baker yeast . Plasma insulin response to this type of bread showed lower values at 30 min ( p = 0.045 ) and a smaller AUC Δ 0–30 min ( p = 0.018 ) . This study shows that in subjects with IGT glycaemic and insulinaemic responses after the consumption of sourdough bread are lower than after the bread leavened with baker yeast . This effect is likely due to the lactic acid produced during dough leavening as well as the reduced availability of simple carbohydrates . Thus , sourdough bread may potentially be of benefit in subjects with impaired glucose metabolism", "BACKGROUND Recent studies have reported beneficial effects of probiotics on maternal glycemia in healthy pregnant women . Obesity significantly increases risk of impaired glucose tolerance in pregnancy , but glycemic effects of probiotics in this specific obstetric group require additional investigation . OBJECTIVE The aim of the Probiotics in Pregnancy Study was to investigate the effect of a probiotic capsule on maternal fasting glucose in obese pregnant women . DESIGN In this placebo-controlled , double-blind , r and omized trial , 175 pregnant women with an early pregnancy body mass index ( BMI ; in kg/m² ) from 30.0 to 39.9 were recruited from antenatal clinics at the National Maternity Hospital , Dublin , Irel and . Exclusion criteria were BMI 39.9 , prepregnancy or gestational diabetes , age Women were r and omly assigned to receive either a daily probiotic or a placebo capsule from 24 to 28 wk of gestation in addition to routine antenatal care . The primary outcome was the change in fasting glucose between groups from preintervention to postintervention . Secondary outcomes were the incidence of gestational diabetes and neonatal anthropometric measures . RESULTS In 138 women who completed the study ( 63 women in the probiotic group ; 75 women in the placebo group ) , mean ( ±SD ) early pregnancy BMI was 33.6 ± 2.6 , which differed significantly between probiotic ( 32.9 ± 2.4 ) and placebo ( 34.1 ± 2.7 ) groups . With adjustment for BMI , the change in maternal fasting glucose did not differ significantly between treated and control groups [ -0.09 ± 0.27 compared with -0.07 ± 0.39 mmol/L ; P = 0.391 ; B = -0.05 ( 95 % CI : -0.17 , 0.07 ) ] . There were also no differences in the incidence of impaired glycemia ( 16 % in the probiotic group compared with 15 % in the placebo group ; P = 0.561 ) , birth weight ( 3.70 kg in the probiotic group compared with 3.68 kg in the placebo group ; P = 0.723 ) , or other metabolic variables or pregnancy outcomes . A secondary analysis of 110 women , excluding antibiotic users and poor compliers , also revealed no differences in maternal glucose or other outcomes between groups . CONCLUSION Probiotic treatment of 4 wk during pregnancy did not influence maternal fasting glucose , the metabolic profile , or pregnancy outcomes in obese women", "OBJECTIVE To observe the influences of bifidobacterium on glucose and lipid metabolism and intestinal flora in type 2 diabetes mellitus rats . METHODS Rats were r and omly divided into 4 groups , the blank control group was fed with basic forage , the other 3 groups were fed with high fat diet . Meanwhile the high-dose and low-dose groups were gavage administrated with 12 and 4 ml/(kg x d ) probiotic bifidobacterium for 6 weeks , then , injected with low dose of streptozotocin ( 20 mg/kg ) . All rats were sacrificed 2 weeks later , blood and feces sample s were collected to analyse . RESULTS Compared with rats of type 2 diabetes model , glucose concentrations and serum concentrations of FFA , TG , LDL-C of 2 experimental groups were significantly lower , serum concentrations of HDL-C were higher , insulin sensitivity index was higher , content of bifidobacterium was higher , but there were no significant differences in other 5 bacteria . CONCLUSION The probiotic bifidobacterium could significantly ameliorate the disorder of glucose and lipid metabolism , increase the amount of bifidobacterium of type 2 diabetes rats", "Summary The action of gliclazide , a sulphonylurea with beneficial extrapancreatic effects in diabetes , may be enhanced by administering probiotics . The aim of this study was to investigate the influence of probiotics on gliclazide pharmacokinetics and the effect of both probiotics and gliclazide on blood glucose levels in healthy and diabetic rats . Male Wistar rats ( 2 to 3 months , weight 350 ± 50 g ) were r and omly allocated to 4 groups ( n = 10 ) , two of which were treated with alloxan i.v . 30 mg/kg to induce diabetes . One group of healthy and one group of diabetic rats were then gavaged with probiotics ( 75 mg/kg ) for three days after which a gliclazide suspension ( 20 mg/kg ) was administered by gavage to all groups . Blood sample s were collected from the tail vein at various time points for 10 hours post-administration for the determination of blood glucose and gliclazide serum concentrations . It was found that probiotic treatment had no effect on blood glucose levels in healthy rats , but it reduced them ( up to 2-fold;p reduced gliclazide bioavailability in healthy rats ( 3-fold ) whereas it increased gliclazide bioavailability in diabetic rats ( 2-fold;p ) . Gliclazide had no effect on blood glucose levels in either healthy or diabetic rats despite the changes in its bioavailability . In conclusion , the probiotic treatment of diabetic rats increases gliclazide bioavailability and lowers blood glucose levels by insulin-independent mechanisms , suggesting that the administration of probiotics may be beneficial as adjunct therapy in the treatment of diabetes", " At 25 children with insulin dependent diabetes mellitus ( IDDM , Type I ) in a decompensation stage was estimated efficiency of correction secondary hyperlipidemia . The basic group ( n = 11 ) along with insulinotherapy and a lipotrophic preparation ( methionine ) accepted probiotic Bifiform Baby in a dose 0.5 g once a day within 10 days ; the comparison group ( n = 14 ) received insulin therapy and a lipotrophic preparation . Efficiency of treatment was estimated on dynamics of lipids in serum of blood : triglycerides ( TG ) , the total cholesterol ( TH ) , betalipoproteides ( BLP ) . At patients of the basic group authentic decrease TG , TH , BLP was established ; at patients of group of comparison -- decrease TH and BLP . Advantage of therapy secondary hyperlipidemia at children with diabetic ketoacidosis with use of Bifiform Baby consists in the elimination of the main infringement of a metabolismus of lipids in the given disease -- hypertriglyceridemia", "The purpose of this study was to investigate the effects of probiotic and conventional yogurt on the lipid profile in type 2 diabetic people . In a r and omized double-blind controlled trial , 60 people ( 23 males and 37 females ) with type 2 diabetes and low-density lipoprotein cholesterol ( LDL-C ) greater than 2.6 mmol/L were assigned to 2 groups . Participants consumed daily 300 g of probiotic yogurt containing Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 or 300 g of conventional yogurt for 6 wk . Fasting blood sample s , anthropometric measurements and 3-d , 24-h dietary recalls were collected at the baseline and at the end of the trial . Probiotic yogurt consumption caused a 4.54 % decrease in total cholesterol and a 7.45 % decrease in LDL-C compared with the control group . No significant changes from baseline were shown in triglyceride and high-density lipoprotein cholesterol ( HDL-C ) in the probiotic group . The total cholesterol : HDL-C ratio and LDL-C : HDL-C ratio as atherogenic indices significantly decreased in the probiotic group compared with the control group . Probiotic yogurt improved total cholesterol and LDL-C concentrations in type 2 diabetic people and may contribute to the improvement of cardiovascular disease risk factors" ]	41189316-06ff-11f0-808a-c43d1ab1c353
Purpose of Review We performed a systematic review to eluci date the current guidelines on weaning patients from opioids in the post-operative ambulatory surgery setting , and how pain management intraoperatively can impact this process . Design The review highlights the most up-to- date research from clinical trials , patient reports , and retrospective studies regarding both the current guidelines and weaning of opioid analgesia in ambulatory surgery setting .Recent Findings A striking paucity of convincing evidence exists on ambulatory postoperative pain management discontinuation or weaning of pain medications . However , retrospective and patient-reported studies suggest our approach should be similar to acute pain management strategies . The first steps include identifying high-risk patients and devising an appropriate pain plan . This may be accomplished by implementing multimodal analgesia , anticipating opioid needs , and the proper use of regional anesthesia . The increasing roles for Transitional Pain Service ( TPS ) , Perioperative Surgical Home ( PSH ) , and Enhanced Recovery After Surgery ( ERAS ) may also guide us in this process . Summary Patients discharged from same-day surgery may lack the additional infrastructure of a hospital or medical establishment to monitor postoperative recovery . As such , weaning of pain medications in ambulatory surgery setting s requires teams that are adept at treating varied patient population s through a tailored , novel means that invoke multimodal analgesia . Given the growth of surgeries moving toward the ambulatory sector , more data and practice guidelines are needed to direct postoperative pain regimen titration for the patients	[ "Background and Objectives An increasing percentage of all surgery is performed in an ambulatory surgery setting . Concurrently , arthroscopy of the shoulder joint has allowed definitive repair of shoulder pathology to occur in this environment . This study was design ed to ascertain whether interscalene block is reliable and efficient for use in same-day surgery compared with general anesthesia for shoulder arthroscopy . Methods The authors retrospectively review ed patients treated at the University of Connecticut over a 42-month period in the same-day surgery unit . Of 263 patients , 160 had a general anesthetic and 103 had an interscalene block . All times recorded for the study were contemporaneously logged into the operating room computer data base from which they were extracted . Data on complications were retrieved from individual patient charts and hospital quality assurance files . Results Compared to general anesthesia , regional anesthesia required significantly less total nonsurgical intraoperative time use ( 53 ± 12 vs. 62 ± 13 minutes , P = .0001 ) and also decreased postanesthesia care unit stay ( 72 ± 24 vs. 102 ± 40 , P = .0001 ) . Interscalene block anesthesia result ed in significantly fewer unplanned admissions for therapy of severe pain , sedation , or nausea/vomiting than general anesthesia ( 0 vs. 13 , P = .004 ) and an acceptable failure rate ( 8.7 % ) . Conclusions Interscalene block should be considered as a viable alternative to general anesthesia for shoulder arthroscopy in ambulatory surgery patients", "OBJECTIVE Preoperative determinants of pain duration following surgery are poorly understood . We identified preoperative predictors of prolonged pain after surgery in a mixed surgical cohort . METHODS We conducted a prospect i ve longitudinal study of patients undergoing mastectomy , lumpectomy , thoracotomy , total knee replacement , or total hip replacement . We measured preoperative psychological distress and substance use , and then measured pain and opioid use after surgery until patients reported the cessation of both opioid consumption and pain . The primary endpoint was time to opioid cessation , and those results have been previously reported . Here , we report preoperative determinants of time to pain resolution following surgery in Cox proportional hazards regression . RESULTS Between January 2007 and April 2009 , we enrolled 107 of 134 consecutively approached patients undergoing the aforementioned surgical procedures . In the final multivariate model , preoperative self-perceived risk of addiction predicted more prolonged pain . Unexpectedly , anxiety sensitivity predicted more rapid pain resolution after surgery . Each one-point increase ( on a four point scale ) of self-perceived risk of addiction was associated with a 38 % ( 95 % CI 3 - 61 ) reduction in the rate of pain resolution ( P = 0.04 ) . Furthermore , higher anxiety sensitivity was associated with an 89 % ( 95 % CI 23 - 190 ) increased rate of pain resolution ( P = 0.004 ) . CONCLUSIONS Greater preoperative self-perceived risk of addiction , and lower anxiety sensitivity predicted a slower rate of pain resolution following surgery . Each of these factors was a better predictor of pain duration than preoperative depressive symptoms , post-traumatic stress disorder symptoms , past substance use , fear of pain , gender , age , preoperative pain , or preoperative opioid use", "Postoperative pain is a common reason for the delayed discharge and unanticipated hospital admission of out patients .In this study , we examined the pattern of pain in ambulatory surgical patients and determined those factors that predict postoperative pain . Ten thous and eight consecutive ambulatory surgical patients were prospect ively studied . Preoperative patient characteristics , intraoperative variables , and pain in the postanesthesia care unit ( PACU ) and the ambulatory surgical unit ( ASU ) and 24 h postoperatively were documented . The incidence of severe pain was 5.3 % in the PACU , 1.7 % in the ASU , and 5.3 % 24 h postoperatively . In the PACU , younger male adults ( 36 + /- 13 vs 47 + /- 22 yr ) , ASA physical status I patients , and patients with a higher body mass index ( 26 + /- 5 vs 25 + /- 5 kg ) had a higher incidence of severe pain . In the group with severe pain , the duration of anesthesia , the duration of stay in the PACU and the ASU , and the time to discharge was longer than in the group without severe pain . In the PACU , orthopedic patients had the highest incidence of pain ( 16.1 % ) , followed by urologic ( 13.4 % ) , general surgery ( 11.5 % ) , and plastic surgery ( 10.0 % ) patients . In patients who had general anesthesia , the intraoperative dose of fentanyl was significantly smaller in the group with severe pain than in the group without severe pain when body mass index and duration of anesthesia were taken into consideration . Body mass index , duration of anesthesia , and certain types of surgery were significant predictors of severe pain in the PACU . This knowledge will allow us to identify those patients at risk of severe postoperative pain and manage them prophylactically . Implication s : The pattern of pain was examined in 10,008 consecutive ambulatory surgical patients . The incidence of severe pain was 5.3 % in the postanesthesia care unit , 1.7 % in the ambulatory surgical unit , and 5.3 % 24 h postoperatively . Body mass , duration of anesthesia , and certain types of surgery were significant predictors of pain in the postanesthesia care unit . These data will allow us to better predict those patients who need intense prophylactic analgesic therapy . ( Anesth Analg 1997;85:808 - 16", "Background Laparoscopic cholecystectomy has been performed as a day-case procedure for over a decade . This procedure can be associated with a high incidence of pain and post-operative nausea and vomiting ( PONV ) . There is a paucity of information regarding the post-discharge care of these patients . Aims To determine the effectiveness and adequacy of take-home analgesic packs given to patients undergoing ambulatory surgery . Methods A prospect i ve study of 40 patients undergoing laparoscopic cholecystectomy to evaluate post-operative pain , analgesia requirements and PONV following discharge . Data regarding unplanned admissions , patient satisfaction and GP attendance rates were also recorded . Results At 24 h , 65 % of patients reported moderate pain , 23 % severe pain and 25 % of patients reported PONV . The rate of GP attendance for further analgesia or antiemetics was 12.5 % . Unexpected admission rate was 10 % . Conclusion The incidence of PONV post-discharge suggests that adding an antiemetic to our take-home analgesic packs may improve patient comfort . The 2-day supply of diclofenac and co-codamol could also be extended as 65 % of patients had moderate to severe pain . The information gathered shows the importance of post-discharge follow-up of ambulatory surgery patients", "BACKGROUND : Determinants of the duration of opioid use after surgery have not been reported . We hypothesized that both preoperative psychological distress and substance abuse would predict more prolonged opioid use after surgery . METHODS : Between January 2007 and April 2009 , a prospect i ve , longitudinal inception cohort study enrolled 109 of 134 consecutively approached patients undergoing mastectomy , lumpectomy , thoracotomy , total knee replacement , or total hip replacement . We measured preoperative psychological distress and substance use , and then measured the daily use of opioids until patients reported the cessation of both opioid consumption and pain . The primary end point was time to opioid cessation . All analyses were controlled for the type of surgery done . RESULTS : Overall , 6 % of patients continued on new opioids 150 days after surgery . Preoperative prescribed opioid use , depressive symptoms , and increased self-perceived risk of addiction were each independently associated with more prolonged opioid use . Preoperative prescribed opioid use was associated with a 73 % ( 95 % confidence interval [ CI ] 0.51%–87 % ) reduction in the rate of opioid cessation after surgery ( P = 0.0009 ) . Additionally , each 1-point increase ( on a 4-point scale ) of self-perceived risk of addiction was associated with a 53 % ( 95 % CI 23%–71 % ) reduction in the rate of opioid cessation ( P = 0.003 ) . Independent of preoperative opioid use and self-perceived risk of addiction , each 10-point increase on a preoperative Beck Depression Inventory II was associated with a 42 % ( 95 % CI 18%–58 % ) reduction in the rate of opioid cessation ( P = 0.002 ) . The variance in the duration of postoperative opioid use was better predicted by preoperative prescribed opioid use , self-perceived risk of addiction , and depressive symptoms than postoperative pain duration or severity . CONCLUSIONS : Preoperative factors , including legitimate prescribed opioid use , self-perceived risk of addiction , and depressive symptoms each independently predicted more prolonged opioid use after surgery . Each of these factors was a better predictor of prolonged opioid use than postoperative pain duration or severity", "We assessed the effect of small clonidine doses on anxiolysis , analgesia , and hemodynamic stability in patients undergoing abdominal hysterectomy . A total of 61 patients , ASA status I – II , were r and omly assigned to receive either oral clonidine 100 & mgr;g ( n = 29 ) or placebo ( n = 32 ) before surgery and 24 h after surgery . The use of clonidine result ed in anxiolysis and analgesia throughout the 72 h after surgery , although the subjects who received clonidine were sleepier than the control group for the first 6 h after surgery . The number needed to treat was 3 ( 95 % confidence interval [ CI ] , 1.72–9.42 ) to prevent intense anxiety in patients with moderate to intense postoperative pain , compared with 40 ( 95 % CI , 18.79–99.68 ) in the absence of pain or with mild pain . In the treated patients , 68 % had an average heart rate less than 70 bpm during surgery , compared with 21.40 % in the placebo group ( number needed to treat , 2 ; 95 % CI , 1.29–2.80 ) . The clonidine patients required small ropivacaine doses during the surgery but not less morphine by patient-controlled analgesia . A clinical ly relevant anxiolytic effect was found in patients who received oral clonidine in the perioperative period , and this suggests that clonidine might be a useful therapeutic alternative to other preoperative sedatives", "Background Rapid development of acute opioid tolerance is well established in animals and is more likely to occur with large doses of short-acting drugs . The authors therefore tested the hypothesis that intraoperative remifentanil administration results in acute opioid tolerance that is manifested by increased postoperative pain and opioid requirement . Methods Fifty adult patients undergoing major abdominal surgery were r and omly assigned to two anesthetic regimens : ( 1 ) desflurane was kept constant at 0.5 minimum alveolar concentrations and a remifentanil infusion was titrated to autonomic responses ( remifentanil group ) ; or ( 2 ) remifentanil at 0.1 & mgr;g · kg−1 · min−1 and desflurane titrated to autonomic responses ( desflurane group ) . All patients were given a bolus of 0.15 mg/kg morphine 40 min before the end of surgery . Morphine was initially titrated to need by postanesthesia care nurses blinded to group assignment . Subsequently , patients —who were also blinded to group assignment — controlled their own morphine administration . Pain scores and morphine consumption were recorded for 24 postoperative h. Results The mean remifentanil infusion rate was 0.3 ± 0.2 & mgr;g · kg−1 · min−1 in the remifentanil group , which was significantly greater than in the desflurane group . Intraoperative hemodynamic responses were similar in each group . Postoperative pain scores were significantly greater in the remifentanil group . These patients required morphine significantly earlier than those in the desflurane group and needed nearly twice as much morphine in the first 24 postoperative h : 59 mg ( 25–75 % interquartile range , 43–71 ) versus 32 mg ( 25–75 % interquartile range , 19–59;P increased postoperative pain and morphine consumption . These data suggest that remifentanil causes acute opioid tolerance and hyperalgesia ", "OBJECTIVE To determine patient satisfaction with postoperative pain control after ambulatory gynaecologic laparoscopic surgery . METHODS A prospect i ve cohort study in a major tertiary care centre was performed to assess patient satisfaction with postoperative analgesia on the day of surgery and on postoperative days one and two . Data were collected either by telephone or mail-in question naire on each postoperative day . Each patient rated her level of satisfaction according to a 5-point scale at the end of each postoperative day as an average for that day . The final outcome was recorded as either satisfied , with all days classified as \" very satisfied \" or \" perfectly satisfied , \" or unsatisfied , if any single day was rated as \" not satisfied at all , \" \" only slightly satisfied , \" or \" somewhat or partly satisfied . \" RESULTS Forty-nine patients completed the question naire . Surgical procedures included tubal ligation with cautery ( 20 ) , ovarian cystectomy ( 5 ) , oophorectomy ( 2 ) , diagnostic laparoscopy ( 14 ) , and Burch procedure ( 8) . Sixty percent of patients ( 30/49 ) were classified as satisfied with their level of postoperative analgesia . CONCLUSION Only 60 % of patients undergoing gynaecologic laparoscopy as day surgery were satisfied with postoperative pain control . This is suboptimal , particularly in light of the ongoing trend towards more complex procedures being performed as day surgery via minimally invasive techniques", "Background : The purpose of this prospect i ve , r and omized study was to evaluate the time required to perform anaesthesia , achieve surgical block and fulfil st and ardized discharge criteria in out patients receiving knee arthroscopy with either spinal anaesthesia or combined sciatic‐femoral nerve block ", "he combination of oral codeine and acetamino-phen is often used for postdischarge pain controlafter ambulatory surgery . However , frequentlyreported side effects include sedation , constipation , and nausea ( 1 ) . Furthermore , drugs containing co-deine may be abused ( 2 ) and may result in serious sideeffects when combined with alcohol or benzodiaz-epines . Nonsteroidal antiinflammatory drugs are anonprescription alternative to these drugs . The aim of this study was to compare ibuprofenwith codeine/acetaminophen for pain control duringthe first 72 h after ambulatory surgery", "BACKGROUND Postoperative pain is a major problem in day-case surgery in children . Nonsteroidal antiinflammatory drugs have gained popularity in management of pediatric surgical patients to reduce the need for opioids . The aim of this study was to evaluate the efficacy of different doses of rectal acetaminophen in day-case surgery in children . METHODS A r and omized , double-blinded , placebo-controlled study design was used . Patients ( n = 120 ) were r and omized to receive a single dose of 0 , 20 , 40 , or 60 mg/kg of rectal acetaminophen after induction of anesthesia . General anesthesia was induced by mask ventilation with sevoflurane ( 7 % ) in nitrous oxide and oxygen and maintained with 2.5 - 4.0 % end-tidal sevoflurane . Opioids or local anesthetics were not used . Postoperative pain was evaluated by behavioral assessment and physiologic measurements every 10 min after arrival at the postanesthesia care unit . The pain intensity was scored using a 0 - 100 visual analog scale used in the authors ' clinic . The need for rescue medication , intravenous morphine 0.1 mg/kg , was decided by the nurse , who was unaware of the rectal acetaminophen dose . The parents were interviewed by phone after 24 h regarding pain and its treatment , nausea , and vomiting . Rescue analgesia at home was rectal ibuprofen , 10 mg/kg . RESULTS In the postanesthesia care unit pain scores were significantly lower in the 40- and 60-mg/kg groups compared with placebo and 20-mg/kg groups . Acetaminophen result ed in a dose-related reduction in the number of children who required postoperative rescue opioid , with significance reached with 40 or 60 mg/kg doses . Calculated dose of acetaminophen at which 50 % of the children not requiring a rescue opioid was 35 mg/kg . The need for rescue analgesia at home during the first 24 h after surgery was also significantly less in patients in the 40- or 60-mg/kg groups than in the 0- or 20-mg/kg groups ( 20 - 17 vs. 80 - 63 % ) . Thirty-three percent of patients receiving placebo had postoperative nausea and vomiting , compared with 0 - 3 % in groups receiving 40 or 60 mg/kg acetaminophen . CONCLUSIONS A single dose of 40 or 60 mg/kg of rectal acetaminophen has a clear morphine-sparing effect in day-case surgery in children if administered at the induction of anesthesia . Moreover , children with adequate analgesia with acetaminophen have less postoperative nausea and vomiting", "STUDY OBJECTIVE To evaluate the comparative efficacy and side effect profile of ketorolac 60 mg , dezocine 6 mg , and fentanyl 100 micrograms when used as analgesic supplements to a propofol infusion during monitored anesthesia care ( MAC ) . DESIGN R and omized , double-blind , placebo-controlled study . SETTING Ambulatory surgery facility at a university medical center . PATIENTS 80 out patients undergoing breast biopsy or inguinal herniorraphy procedures under MAC . INTERVENTIONS All patients received midazolam 2 mg intravenously ( IV ) followed by 1 ml of the study medication containing either dezocine 3 mg IV , ketorolac 30 mg IV , fentanyl 50 micrograms IV , or normal saline . A propofol infusion was initiated at 75 micrograms/kg/min and then varied to maintain a stable level of sedation ( i.e. , Observer Assessment of Alertness/Sedation scale score of 3 ) . An additional 1 ml of the same study medication was administered IV 2 to 3 minutes prior to infiltration of the local anesthetic solution . During the operation , supplemental ( rescue ) medication consisted of fentanyl 25 micrograms IV , bolus injections in all four treatment groups . MEASUREMENTS AND MAIN RESULTS Propofol infusion and supplemental fentanyl dosage requirements , oxygen saturation values , respiratory rates , recovery times , and postoperative side effects were recorded . Visual analog scales were used to assess sedation , anxiety , pain , and nausea preoperatively ( baseline ) , upon entry into the postanesthesia care unit , and at 30-minute intervals until discharge . The fentanyl and dezocine groups required lower average infusion rates of propofol to maintain a stable level of sedation than the control ( saline ) group . The saline and ketorolac groups required rescue analgesic medication more frequently and /or larger supplemental dosages of fentanyl than the two opioid analgesic treatment groups . Compared with the three analgesic treatment groups , postoperative pain scores were only marginally higher in the control group . Ketorolac-treated patients had consistently ( but not significantly ) shorter recovery times to oral intake , ambulation , and discharge than those in the dezocine or fentanyl groups . No postoperative nausea , vomiting , or pruritus was reported in the ketorolac group . CONCLUSION Compared with ketorolac 60 mg , fentanyl 100 micrograms and dezocine 6 mg produced a greater decrease in the propofol sedation requirement during MAC . However , the use of ketorolac in combination with propofol for MAC was associated with an improved recovery profile", "BACKGROUND AND AIM Pain after surgery continues to be undermanaged . Studies and initiatives aim ing to improve the management of postoperative pain are growing ; however , most studies focus on in patients and pain on the first day after surgery . The management of postoperative pain after ambulatory surgery and for several days thereafter is not yet a major focus . One reason is the low return rate of the question naires in the ambulatory sector . This article reports the development and feasibility of a web-based electronic data collection system to examine pain and pain-related outcome on predefined postoperative days after ambulatory surgery . MATERIAL AND METHODS In this prospect i ve pilot study 127 patients scheduled for ambulatory surgery were asked to participate in a survey to evaluate aspects related to pain after ambulatory surgery . The data survey was divided in ( 1 ) a preoperative , intraoperative and postoperative part and ( 2 ) a postoperative internet-based electronic question naire which was sent via e-mail link to the patient on days 1 , 3 and 7 after surgery . A software was developed using a PHP-based platform to send e-mails and retrieve the data after web-based entries via a local browser . Feasibility , internet-based hitches and compliance were assessed by an additional telephone call after day 7 . RESULTS A total of 100 patients ( 50 female ) between 18 and 71 years ( mean 39.1 ± 12.7 years ) were included in the pilot study . Return rates of the electronic question naires were 86 % ( days 3 and 7 ) and 91 % ( day 1 after surgery ) . All 3 electronic question naires were answered by 82 % of patients . Aspects influencing the return rate of question naires were work status but not age , gender , education level and preoperative pain . Telephone interviews were performed with 81 patients and revealed high operability of the internet-based survey without any major problems . CONCLUSION The user-friendly feasibility and operability of this internet-based electronic data survey system explain the high compliance and return rate of electronic question naires by patients at home after ambulatory surgery . This survey tool therefore provides unique opportunities to evaluate and improve postoperative pain management after ambulatory surgery" ]	4118935c-06ff-11f0-808a-c43d1ab1c353
Background Muscular fitness ( MF ) is considered a powerful marker of health , but the extent to which common health behaviors are associated with MF during childhood and adolescence is currently unclear . Objective We conducted a systematic review of studies investigating associations between MF ( i.e. , strength/power , local muscular endurance ) and physical activity , sedentary behaviors , and sleep in children and adolescents . Methods A systematic search of six electronic data bases was performed on 8 March , 2017 . Search results were screened for relevance and studies conducted with children and adolescents ( 3–18 years ) that explored associations between MF and physical activity , sedentary behavior , or sleep were considered eligible . Data were extracted and checked by a second author . The proportion of studies reporting a statistically significant association between each MF component and behavioral variables was calculated , and additional coding was conducted to account for risk of bias . Results There was consistent evidence for a positive association between MF and physical activity . For both MF components , there was support for objective ly measured physical activity , particularly for activity of vigorous intensity . Sports participation was also consistently linked with both MF components , whereas the association with active transport was inconsistent . For both MF components , associations with sedentary behaviors were inconsistent irrespective of measurement method , and the association between MF and sleep was considered uncertain . Conclusions The available evidence supports a link between MF and physical activity , particularly for vigorous intensity activity and organized sports participation . Conversely , there is limited support for an association with sedentary behaviors , and more research exploring MF and sleep is required	[ "OBJECTIVE To analyze socioeconomic indicators , physical activity ( PA ) opportunities , and behavioral correlates of cardiorespiratory and muscular fitness among Brazilian boys and girls . METHODS A sample of 1555 adolescents was r and omly selected . Age- and sex-specific st and ard scores were calculated for each fitness component . RESULTS Among boys , head of household 's schooling , involvement in organized PA , meeting the PA recommendations , and computer/games use were associated with cardiorespiratory fitness . Involvement in organized PA and active time in Physical Education ( PE ) classes were predictors of muscular fitness . Among girls , active time in PE classes and TV watching were predictors of cardiorespiratory fitness . Meeting the PA recommendations was associated with muscular fitness . CONCLUSION PA variables and sedentary behaviors should be independently considered for physical fitness promotion in youth", "Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials", "Aims : To investigate how physical activity , physical performance and sociodemographic characteristics at the age of 16 are related to adult health habits ( physical activity , dietary intake , smoking ) and biological risk factors for cardiovascular diseases ( being overweight , low aerobic fitness , unfavorable levels of serum lipids , high blood pressure ) . Methods : A r and omly selected group of 220 male and 205 female students at 16 years of age was tested in 1974 , and reinvestigated 18 years later . Results : The predictive health profiles for adult lifestyle and biological risk factors were different in men and women . Leisure sports activity along with high performance in the nine-minute run among the boys and in the two-h and lift test among the girls were significant predictors of adult physical activity . A positive attitude to aerobic exercise and high performance in the nine-minute run test among the boys and high marks in physical education among the girls decreased the risk of smoking . Leisure sports activities together with body mass index at young ages were the most powerful predictors of adult biological risk factors , but attitudes to sports and educational level were also significant determinants . Conclusion : These results contribute to the knowledge of which factors at young ages may promote adult healthy habits in particular physical activities ", "BACKGROUND Rural children are at a particular high risk for obesity . Given the importance of exercise in obesity and chronic disease prevention , this study evaluated the level and relationship between physical activity and fitness in a sample of rural third grade rs . The second purpose of the study was to determine potential differences in physical activity and fitness level by weight status in this sample . METHODS Twelve schools participating in a multidisciplinary research project were r and omly selected for the study . Body mass index-for-age percentile , the modified Self-administered Physical Activity Checklist , and the FITNESSGRAM battery tests were utilized to determine children 's weight status , physical activity , and fitness level , respectively . RESULTS Thirty-eight percent of the 237 participating children ( 9.2 ± 0.4 years ) were overweight or obese . Nearly 15 % were extremely obese . Children spent 91.8 ± 83.8 and 32.2 ± 47.7 minutes in moderate- and vigorous-intensity activities . Obese children spent less time in moderate-intensity activity ( p combined moderate- and vigorous-intensity activity more than other children ( p the fitness st and ard for muscular strength and 36 % failed to meet it for flexibility . CONCLUSIONS Rural children in this sample had higher rates of obesity compared to the national average ; they had poor fitness and 30 % failed to meet the minimum physical activity recommendations on the previous day . Future interventions should focus on increasing physical activity , especially of moderate-intensity , and improving physical fitness in order to reduce obesity and decrease the risk of future chronic diseases in this high-risk population", "BACKGROUND Childhood obesity has been inconsistently associated with decreased levels of physical activity and fitness . Moreover , little is known about this relationship among Filipino preteens . METHODS This cross sectional study reports the association between childhood obesity , measures of physical activity , and fitness . Children aged 11 to 12 from r and omly selected schools from San Juan , Metromanila were included . Outcome measures were body mass index , Filipino modified Physical Activity Question naire for Older children ( F_PAQ-C ) , st and ing broad jump , 50 m sprint and 20 m multistage shuttle run . RESULTS 380 children participated in the study . Obese children had significantly lower median scores in the F_PAQ-C compared with overweight children . Overweight children had lower scores in the st and ing broad jump , 50 m sprints and predicted VO2max as compared with children with normal BMI . There were modest associations between the 50 m sprint , predicted VO2max , and F_PAQ-C. CONCLUSION Our study has showed that physical activity and fitness scores were strongly correlated with childhood obesity . If childhood physical fitness is a predictor of physical fitness in adulthood which is a risk factor in cardiovascular diseases , there is a strong possibility that the prevalence of cardiovascular disease in the Philippines will increase dramatically in the future", "The aims of this study were to investigate whether physical activity ( PA ) and sedentary time ( ST ) in 9- and 15-year-olds differed between 2005 - 2006 and 2011 - 2012 ( secular change ) , and to investigate changes in PA and ST from age 9 to 15 ( longitudinal change ) . In 2005 - 2006 , we invited nationally representative sample s of Norwegian 9- ( n=1470 ) and 15-year-olds ( n=1348 ) to participate . In 2011 - 2012 , we invited a new nationally representative sample of 9-year-olds ( n=1945 ) , whereas 15-year-olds ( n=1759 ) were invited to participate either based on previous participation in 2005 - 2006 or from a r and om sample of schools . We assessed PA and ST objective ly using accelerometers . In 2011 - 2012 , both 9- and 15-year-olds spent more time sedentary ( ≥35.7 min/d , P in light PA ( ≥35.2 min/d , P in moderate-to-vigorous PA ( MVPA ) ( 4.2 min/d , P=.041 ) . In both age groups , the proportion accumulating an average of 60 min/d of MVPA did not differ between the two cohorts . From age 9 to 15 , girls and boys decreased their time spent in LPA ( ≥106.7 min/d , P and in MVPA ( ≥20.8 min/d , P period , ST increased by a mean of > 2 h/d ( P in PA from 2005 - 2006 to 2011 - 2012 among 9- and 15-year-olds , and a large decline in PA in the participants followed longitudinally from age 9 to 15 years", "Objective To investigate the associations between body composition , cardiorespiratory and muscular fitness in relation to travel mode to school in children and adolescents . Method Children and adolescents from 40 elementary schools and 23 high schools representing all regions in Norway were invited to participate in the study . Anthropometry , cardiorespiratory and muscular fitness were tested at the school location . Question naires were used in order to register mode of transport to school , age , gender and levels of leisure time physical activity . Results A total of 1694 ( i.e. 60 % of all invited participants ) children and adolescents at a mean age of 9.6 and 15.6 respectively ( SD = 0.4 for both groups ) were analyzed for associations with physical fitness variables . Males cycling to school had lower sum of skin folds than adolescents walking to school . Higher cardiorespiratory fitness in adolescents and male cyclists compared to walkers and passive commuters were observed . Among children , cycling and walking to school , higher isometric muscle endurance in the back extensors compared to passive commuters was observed . Conclusion Based on this national representative cross-sectional examination of r and omly selected children and adolescents there is evidence that active commuting , especially cycling , is associated with a favourable body composition and better cardiorespiratory and muscular fitness as compared to passive commuting ", "OBJECTIVE To test the hypothesis that resistance training may increase spontaneous physical activity in children . STUDY DESIGN Two junior ice hockey teams were r and omly assigned to unchanged training schedules ( team ZSC , 21 boys ; mean age , 13.2 years ) or to participate twice weekly in guided resistance training for 4 months ( team GCK , 25 boys ; mean age , 13.4 years ) . Spontaneous physical activity energy expenditure ( SpAEE ; 3-axial accelerometry for 7 days ) , muscle strength , and body composition ( dual energy x-ray absorptiometry ) were measured at 0 , 4 , and 12 months . RESULTS Baseline measures did not differ in the groups , except for higher leg and trunk strength in team ZSC . In the intervention group compared with the control group , SpAEE significantly ( P Leg and arm strength increased because of training intervention ; all other variables were unchanged . None of these variables correlated with changes in SpAEE . CONCLUSION In boys who play ice hockey , spontaneous physical activity is inducible with resistance training ; this effect seems to be independent of changes in body composition and strength . If this was confirmed in unselected children , resistance training might be a new strategy for childhood obesity prevention programs", "OBJECTIVE : To study the effect of physical activity on whole body fat ( BF ) , its regional deposition and the influence of body fatness on physical performance in prepubertal children . DESSIGN : Cross-sectional study .SUBJECTS : A total of 114 boys ( 9.4±1.5 y , Tanner I – II ) , r and omly sample d from the population of Gran Canaria ( Spain ) , 63 of them physically active ( PA , at least 3 h per week during the previous year ) and 51 nonphysically active ( non-PA ) . MEASUREMENTS : Body composition ( DXA ) , anthropometric variables ( body circumferences and skinfolds ) and physical fitness were determined in all subjects . RESULTS : The PA obtained better results in maximal oxygen uptake , isometric leg extension force , vertical jump ( muscular power ) , and 300 m ( anaerobic capacity ) and 30 m running tests ( speed ) than the non-PA . A lower percentage of body fat ( % BF ) ( 4 U less , P whole BF mass ( 36 % less , P and regional fat mass ( 28 , 25 , and 30 % less in the trunk , legs and arms , respectively , all P the PA compared to the non-PA . The waist and hip circumferences correlated more closely with both the fat mass accumulated in the trunk region and the % BF ( r=0.81–0.95 , P the waist-to-hip ratio ( WHR ) . The WHR correlated with the percentage of the whole fat mass accumulated in the trunk ( PFT ) ( r=0.52–0.53 , P the PFT increased curvilinearly with the % BF , regardless of the level of physical activity . ANCOVA analysis revealed that total and regional fat masses explained less than 40 % of the difference in performance between the PA and non-PA group . The mean speed in the 30 m running test ( V30 ) , combined with the height and whole body mass , has predictive value for the BF mass ( R=0.98 , P The % BF may be estimated from the body mass index ( BMI ) and V30 ( % BF=8.09 + 2.44 · BMI ( kg m−2)–5.8·V30 ( m s−1 ) , R=0.94 , P sports activities and competitions on top of the compulsory physical education program is associated with increased physical fitness , lower whole body and trunkal fat mass in prepubertal boys", "Relationships between birthweight and grip strength throughout the life course suggest that early influences on the growth and development of muscle are important for long-term muscle function . However , little is known about parental influences on children 's grip strength . We have explored this in the Southampton Women 's Survey , a prospect i ve general population cohort study from before conception through childhood . Grip strength was measured using a Jamar h and grip dynamometer in the mother at 19 weeks ' gestation and her partner , and in the child at age 4 years . Pre-pregnancy heights and weights were measured in the mothers ; reported weights and measured heights were available for the fathers . Complete data on parents and children were available for 444 trios . In univariable analyses , both parents ' grip strengths were significantly associated with that of the child ( r = 0.17 , P grip strength of the mothers and the fathers ( r = 0.17 , P grip strength were attenuated , being 0.10 ( P = 0.02 ) and 0.11 ( P = 0.01 ) for mothers ' and fathers ' grip strength respectively . The findings show that grip strength of each parent is associated with that of the child , indicating that heritable influences and the shared family environment influence the development of muscle strength . This contributes to our underst and ing of the role of heritable and environmental factors on early muscle growth and development , which are important for muscle function across the life course", "This 12-month prospect i ve controlled intervention evaluated the effect of a general school based physical activity program on muscle strength , physical performance and body composition in prepubertal girls . Fifty-three girls aged 7–9 years involved in a school based exercise program [ 40 min/day of general physical activity per school day ( 200 min/week ) ] were compared with 50 age-matched girls who participated in the general Swedish physical education curriculum ( mean 60 min/week ) . Body composition ( DXA ) , isokinetic peak torque ( PT ) of the knee extensors and flexors at 60 and 180 ° /s , and vertical jump height ( VJH ) were assessed at baseline and 12 months . The annual gain in weight was similar between the groups , but there was a greater increase in total body and regional lean mass ( P and fat mass ( P . Mean gains in knee extensor PT at 60 and 180 ° /s were 7.0–7.6 % greater in the exercise group ( P ranging No significant differences were detected in VJH . In conclusion , increasing school based physical education to at least 3 h/week provides a feasible strategy to enhance the development of muscle strength and lean mass in prepubertal girls", "Abstract The purpose of the present study was to assess different aspects of physical activity and fitness in order to develop a basis for sport programmes for overweight and obese children . Eighty-eight prepubertal children ( 49 boys , 39 girls , 4.8–11.4 years old , 61 % obese , 14 % overweight and 25 % normal weight ) were examined . Body composition was assessed by combined use of anthropometrics and bioelectrical impedance analysis . Resting energy expenditure ( REE ) and total energy expenditure ( TEE ) were measured by indirect calorimetry ( IC ) and individually calibrated 24-h heart rate ( HR ) monitoring , respectively . Activity-related energy expenditure ( AEE ) and physical activity level ( PAL ) were calculated from TEE and REE . Fitness [ assessed by O2-pulse , respiratory exchange ratio ( RER ) at submaximal work intensities ] was determined by ergometry . The maximal isometric muscle strength of the legs ( m. quadriceps , Fa max , m. ischiocruralis , Fb max ) was measured by computer tensiometry . Children were grouped according to their nutritional state , AEE , O2-pulse and muscle strength . When compared with normal weight children , obese and overweight children had increased fat mass ( FM ) , fat-free mass ( FFM ) , waist-to-hip ratio and REE , but no group differences were observed for TEE , AEE , and PAL . Obese and overweight children spent more hours per day watching TV . After correction for body weight and FFM , no group differences in REE were observed , but normal weight children had a higher O2-pulse than overweight and obese children . By contrast , RER was increased in the latter group . The fittest group had the lowest body weight , BMI , FM and FFM . Children with a low O2-pulse spent more hours per day watching TV . Grouping children according to their degree of muscle strength , younger children ( 4–7.5 years ) did not show group differences in nutritional state , energy expenditure , physical activity and fitness . However , in the group of 7.6- to 11-year-old children , those with the greatest muscle strength and FFM had reduced BMI , skin folds , FM and FFM . FM correlated inversely with O2-pulse , but was not associated with TEE , AEE , PAL or muscle strength . By contrast TV consumption was positively associated with FM . To summarize , overweight and obese children were less fit and watched more TV than their normal weight counterparts . FM did not correspond to TEE , AEE or PAL . Muscle strength was not associated with FM in young children , but was inversely associated with FM in older children . Our cross-sectional data are consistent with the idea that increased fitness and reduced physical inactivity may prevent children from being overweight", "The study describe changes over 2 years in different physical fitness measures and the relationship between these changes and changes in physical activity . Maximal aerobic work capacity ( Wattmax ) , functional strength , muscle endurance , agility and flexibility were measured in 259 r and omly selected high school boys and girls 16.5 years of age and followed-up 2 years later , while they still attended school . Most physical fitness measures increased over time in boys , and in girls an increase was found in arm extensor strength and trunk extensor endurance , but Wattmax per kg body mass decreased . Changes in physical performance between 16 and 18 years of age seem to be very similar in different countries , despite differences in physical activity patterns and absolute level of performance . No change was found in time of participation in physical activity or sports activity in either gender , but fewer girls participated in leisure-time sports at the 2nd test ( p physical activity or sports activity did not relate to change in physical fitness level . The relationships between level of sports participation ( competition , for health or none ) and physical fitness measures at baseline and at the 2nd test were weak or non-significant . Three explanations for the weak relationship between physical activity and fitness are suggested : ( A ) part of the variability in fitness is explained by genetics , ( B ) growth and hormonal changes , especially in boys , override the stimulus of training , and ( C ) the physical fitness level in adolescents is so high that only physical activity at high relative intensity is supposed to have an effect on the fitness level", "UNLABELLED Decreased fitness and increased fatness are relevant factors for decreased cardiovascular and bone health in children . One way to increase physical activity and hence fitness and to reduce the risk for overweight might be sports club participation ( SCP ) . PURPOSE To investigate the association of SCP with fatness and fitness in children in general and in those with increased risk for overweight and /or low fitness . METHODS A cross-sectional study was conducted in a r and om sample of 502 first- and fifth- grade primary school children . Fitness components were determined by 10 motor tests and body fatness by the sum of four skinfolds . SCP was defined as participation of at least once a week . RESULTS Two thirds of all children were participating in a sports club . Girls ' and boys ' participation rate as well as those of overweight children and of children with overweight parents were comparable to their respective normal weight peers . In contrast , children from migrant families ( odds ratio = 0.31 ; 95 % confidence interval = 0.20 - 0.48 ) and from inactive parents ( odds ratio = 0.16 ; 95 % confidence interval = 0.05 - 0.45 ) participated significantly less ( all P endurance ( 0.53 > beta > 0.37 , all P speed , strength , and coordination ( 0.41 > beta > 0.18 , all P overweight children and in children from overweight parents and migrant families , this association was not found . There was no association between SCP and fatness in any of the groups . CONCLUSIONS SCP rates were high and were associated with higher levels of most fitness components in children . Participation rates were lower for children of migrant families and children from inactive parents . In addition , the association between SCP and fitness components was not found in overweight children and in children from overweight parents and migrant families", "Background The aim of this study was to investigate how sleep , screen time , active school travel and sport and /or exercise participation associates with moderate-to-vigorous physical activity ( MVPA ) in nationally representative sample s of Norwegian 9- and 15-y-olds , and whether these four behaviors at age nine predict change in MVPA from age nine to 15 years . Method We pooled cross-sectional accelerometer and question naire data from 9- ( n = 2366 ) and 15-y-olds ( n = 1554 ) that participated in the first ( 2005/06 ) and second ( 2011/12 ) wave of the Physical Activity among Norwegian Children Study to investigate cross-sectional associations . To investigate prospect i ve associations , we used data from a sub- sample that participated in both waves ( at age nine and 15 years , n = 517 ) . Results Cross-sectional analyses indicated a modest , inverse association between screen time and MVPA among 9- ( − 2.2 min/d ( 95 % CI : -3.1 , − 1.3 ) ) and 15-y-olds ( − 1.7 min/d ( 95 % CI : -2.7 , − 0.8 ) ) . Compared to their peers with 0–5 min/d of active travel to school , 9- and 15-y-olds with ≥16 min/d accumulated 7.2 ( 95 % CI : 4.0 , 10.4 ) and 9.0 ( 95 % CI : 3.8 , 14.1 ) more min/d of MVPA , respectively . Nine-y-old boys and 15-y-olds reporting ≥8 h/week of sports and /or exercise participation accumulated 14.7 ( 95 % CI : 8.2 , 21.3 ) and 17.9 ( 95 % CI : 14.0 , 21.8 ) more min/d of MVPA , respectively , than those reporting ≤2 h/week . We found no cross-sectional association between sleep duration and MVPA in either age group . None of the four behaviors predicted change in MVPA from age nine to 15 years ( p ≥ 0.102 ) . Conclusion Active travel to school and sport/exercise participation may be important targets for future interventions aim ed at increasing MVPA in children and adolescents . However , future studies are needed to determine causality" ]	41189398-06ff-11f0-808a-c43d1ab1c353
Enhanced recovery after surgery ( ERAS ) pathways are now implemented worldwide with strong evidence that adhesion to such protocol reduces medical complications , costs and hospital stay . This concept has been applied for pancreatic surgery since the first published guidelines in 2012 . This study presents the up date d ERAS recommendations for pancreatoduodenectomy ( PD ) based on the best available evidence and on expert consensus . A systematic literature search was conducted in three data bases ( Embase , Medline Ovid and Cochrane Library Wiley ) for the 27 developed ERAS items . Quality of r and omized trials was assessed using the Consoli date d St and ards of Reporting Trials statement checklist . The level of evidence for each item was determined using the Grading of Recommendations Assessment Development and Evaluation system . The Delphi method was used to vali date the final recommendations . A total of 314 articles were included in the systematic review . Consensus among experts was reached after three rounds . A well-implemented ERAS protocol with good compliance is associated with a reduction in medical complications and length of hospital stay . The highest level of evidence was available for five items : avoiding hypothermia , use of wound catheters as an alternative to epidural analgesia , antimicrobial and thromboprophylaxis protocol s and preoperative nutritional interventions for patients with severe weight loss ( > 15 % ) . The current up date d ERAS recommendations for PD are based on the best available evidence and processed by the Delphi method . Prospect i ve studies of high quality are encouraged to confirm the benefit of current up date d recommendations	[ "BACKGROUND The benefits of preoperative biliary drainage , which was introduced to improve the postoperative outcome in patients with obstructive jaundice caused by a tumor of the pancreatic head , are unclear . METHODS In this multicenter , r and omized trial , we compared preoperative biliary drainage with surgery alone for patients with cancer of the pancreatic head . Patients with obstructive jaundice and a bilirubin level of 40 to 250 micromol per liter ( 2.3 to 14.6 mg per deciliter ) were r and omly assigned to undergo either preoperative biliary drainage for 4 to 6 weeks , followed by surgery , or surgery alone within 1 week after diagnosis . Preoperative biliary drainage was attempted primarily with the placement of an endoprosthesis by means of endoscopic retro grade cholangiopancreatography . The primary outcome was the rate of serious complications within 120 days after r and omization . RESULTS We enrolled 202 patients ; 96 were assigned to undergo early surgery and 106 to undergo preoperative biliary drainage ; 6 patients were excluded from the analysis . The rates of serious complications were 39 % ( 37 patients ) in the early-surgery group and 74 % ( 75 patients ) in the biliary-drainage group ( relative risk in the early-surgery group , 0.54 ; 95 % confidence interval [ CI ] , 0.41 to 0.71 ; P Preoperative biliary drainage was successful in 96 patients ( 94 % ) after one or more attempts , with complications in 47 patients ( 46 % ) . Surgery-related complications occurred in 35 patients ( 37 % ) in the early-surgery group and in 48 patients ( 47 % ) in the biliary-drainage group ( relative risk , 0.79 ; 95 % CI , 0.57 to 1.11 ; P=0.14 ) . Mortality and the length of hospital stay did not differ significantly between the two groups . CONCLUSIONS Routine preoperative biliary drainage in patients undergoing surgery for cancer of the pancreatic head increases the rate of complications . ( Current Controlled Trials number , IS RCT N31939699 .", "Background Whether octreotide prevents pancreatic fistula following pancreatoduodenectomy is controversial and it is believed to be beneficial in soft gl and s and normal-sized ducts . The aim of this study is to assess the potential value of octreotide in reducing the incidence of pancreatic fistula , postoperative complications , morbidity and hospital stay in patients with soft pancreas and non-dilated ducts . Methods A total of 109 patients undergoing elective pancreatoduodenectomy with soft pancreas and non-dilated duct were r and omized to octreotide group versus no octreotide — the control group . Surgical steps were st and ardized and incidences of pancreatic fistula , complications , death and hospital stay were assessed . Results There were 55 patients in octreotide group and 54 in the control group . Demographic features and pancreatic duct diameter of the groups were comparable . The rates of clinical ly significant pancreatic fistulae ( grade s B and C ) were 10.9 and 18.5 % ( p = ns ) , and morbidity was 18 and 29.6 % ( p = ns ) , respectively . Patients who received octreotide resumed oral diet early and had a shorter hospital stay . Conclusion This study demonstrated no statistical difference in pancreatic fistulae with the use of octreotide , though there was a trend towards fewer incidences of pancreatic fistulae , morbidity and shorter hospital stay . Clinical Trials.gov Identifier :", "BACKGROUND Mild perioperative hypothermia , which is common during major surgery , may promote surgical-wound infection by triggering thermoregulatory vasoconstriction , which decreases subcutaneous oxygen tension . Reduced levels of oxygen in tissue impair oxidative killing by neutrophils and decrease the strength of the healing wound by reducing the deposition of collagen . Hypothermia also directly impairs immune function . We tested the hypothesis that hypothermia both increases susceptibility to surgical-wound infection and lengthens hospitalization . METHODS Two hundred patients undergoing colorectal surgery were r and omly assigned to routine intraoperative thermal care ( the hypothermia group ) or additional warming ( the normothermia group ) . The patient 's anesthetic care was st and ardized , and they were all given cefam and ole and metronidazole . In a double-blind protocol , their wounds were evaluated daily until discharge from the hospital and in the clinic after two weeks ; wounds containing culture-positive pus were considered infected . The patients ' surgeons remained unaware of the patients ' group assignments . RESULTS The mean ( + /- SD ) final intraoperative core temperature was 34.7 + /- 0.6 degrees C in the hypothermia group and 36.6 + /- 0.5 degrees C in the normothermia group ( P Surgical-wound infections were found in 18 of 96 patients assigned to hypothermia ( 19 percent ) but in only 6 of 104 patients assigned to normothermia ( 6 percent , P = 0.009 ) . The sutures were removed one day later in the patients assigned to hypothermia than in those assigned to normothermia ( P = 0.002 ) , and the duration of hospitalization was prolonged by 2.6 days ( approximately 20 percent ) in hypothermia group ( P = 0.01 ) . CONCLUSIONS Hypothermia itself may delay healing and predispose patients to wound infections . Maintaining normothermia intraoperatively is likely to decrease the incidence of infectious complications in patients undergoing colorectal resection and to shorten their hospitalizations", "Background Postoperative ileus is common after surgery . One non-pharmacological intervention that has shown promising results in reducing the duration of postoperative ileus is chewing gum after surgery . However , this has not been investigated in upper gastrointestinal surgery such as pancreatic surgery . Hence the aim of this study was to investigate the effects of chewing gum treatment on patients undergoing pancreaticoduodenectomy ad modum whipple due to pancreatic or periampullary cancer . Methods This study was conducted as a phase III trial that was terminated early . Patients diagnosed with pancreatic tumours scheduled for pancreaticoduodenectomy ad modum whipple were included . The treatment group received chewing gum postoperatively and st and ard care . Controls received glucose solution and st and ard care . Chewing gum and glucose were used four times a day during the whole hospital stay . Time to first flatus and stool was defined as the primary outcome . The secondary outcome was start with clear liquids , start with liquid diet and length of hospital stay . Results No statistically significant differences could be observed between the chewing gum intervention group and the control group . However , a numerical difference in mean time was observed in first flatus , first stool , start of clear fluids , and start of liquid diet and length of hospital stay in favour of the intervention group . Conclusions Although this study did not find statistically significant differences favouring the use of chewing gum for postoperative ileus , a positive trend was observed of a reduction of the impact of postoperative ileus among patients after pancreatic surgery . It also contributes valuable method ological experience that is important for future studies of chewing gum interventions during recovery after pancreatic surgery . Trial registration Clinical Trials.gov identifier : NCT02319512 , publication date 2014 - 12 - 17", "Summary Background Data : The epidemiology of venous thromboembolism ( VTE ) after cancer surgery is based on clinical trials on VTE prophylaxis that used venography to screen deep vein thrombosis ( DVT ) . However , the clinical relevance of asymptomatic venography-detected DVT is unclear , and the population of these clinical trials is not necessarily representative of the overall cancer surgery population . Objective : The aim of this study was to evaluate the incidence of clinical ly overt VTE in a wide spectrum of consecutive patients undergoing surgery for cancer and to identify risk factors for VTE . Methods : @RISTOS was a prospect i ve observational study in patients undergoing general , urologic , or gynecologic surgery . Patients were assessed for clinical ly overt VTE occurring up to 30 ± 5 days after surgery or more if the hospital stay was longer than 35 days . All outcome events were evaluated by an independent Adjudication Committee . Results : A total of 2373 patients were included in the study : 1238 ( 52 % ) undergoing general , 685 ( 29 % ) urologic , and 450 ( 19 % ) gynecologic surgery . In-hospital prophylaxis was given in 81.6 % and postdischarge prophylaxis in 30.7 % of the patients . Fifty patients ( 2.1 % ) were adjudicated as affected by clinical ly overt VTE ( DVT , 0.42 % ; nonfatal pulmonary embolism , 0.88 % ; death 0.80 % ) . The incidence of VTE was 2.83 % in general surgery , 2.0 % in gynecologic surgery , and 0.87 % in urologic surgery . Forty percent of the events occurred later than 21 days from surgery . The overall death rate was 1.72 % ; in 46.3 % of the cases , death was caused by VTE . In a multivariable analysis , 5 risk factors were identified : age above 60 years ( 2.63 , 95 % confidence interval , 1.21–5.71 ) , previous VTE ( 5.98 , 2.13–16.80 ) , advanced cancer ( 2.68 , 1.37–5.24 ) , anesthesia lasting more than 2 hours ( 4.50 , 1.06–19.04 ) , and bed rest longer than 3 days ( 4.37 , 2.45–7.78 ) . Conclusions : VTE remains a common complication of cancer surgery , with a remarkable proportion of events occurring late after surgery . In patients undergoing cancer surgery , VTE is the most common cause of death at 30 days after surgery", "Objective To evaluate the endpoints of complications ( specifically pancreatic fistula and total complications ) and death in patients undergoing pancreaticoduodenectomy . Summary Background Data Four r and omized , placebo-controlled , multicenter trials from Europe have evaluated prophylactic octreotide ( the long-acting synthetic analog of native somatostatin ) in patients undergoing pancreatic resection . Each trial reported significant decreases in overall complication rates , and two of the four reported significantly lowered rates of pancreatic fistula in patients receiving prophylactic octreotide . However , none of these four trials studied only pancreaticoduodenal resections , and all trials had high pancreatic fistula rates ( > 19 % ) in the placebo group . A fifth r and omized trial from the United States evaluated the use of prophylactic octreotide in patients undergoing pancreaticoduodenectomy and found no benefit to the use of octreotide . Prophylactic use of octreotide adds more than $ 75 to the daily hospital charge in the United States . In calendar year 1996 , 288 patients received octreotide on the surgical service at the authors ’ institution , for total billed charges of $ 74,652 . Methods Between February 1998 and February 2000 , 383 patients were recruited into this study on the basis of preoperative anticipation of pancreaticoduodenal resection . Patients who gave consent were r and omized to saline control versus octreotide 250 & mgr;g subcutaneously every 8 hours for 7 days , to start 1 to 2 hours before surgery . The primary postoperative endpoints were pancreatic fistula , total complications , death , and length of hospital stay . Results Two hundred eleven patients underwent pancreaticoduodenectomy with pancreatic-enteric anastomosis , received appropriate saline/octreotide doses , and were available for endpoint analysis . The two groups were comparable with respect to demographics ( 54 % male , median age 66 years ) , type of pancreaticoduodenal resection ( 60 % pylorus-preserving ) , type of pancreatic-enteric anastomosis ( 87 % end-to-side pancreaticojejunostomy ) , and pathologic diagnosis . The pancreatic fistula rates were 9 % in the control group and 11 % in the octreotide group . The overall complication rates were 34 % in the control group and 40 % in the octreotide group ; the in-hospital death rates were 0 % versus 1 % , respectively . The median postoperative length of hospital stay was 9 days in both groups . Conclusions These data demonstrate that the prophylactic use of perioperative octreotide does not reduce the incidence of pancreatic fistula or total complications after pancreaticoduodenectomy . Prophylactic octreotide use in this setting should be eliminated , at a considerable cost savings", "Laparoscopic resection as an alternative to open pancreatoduodenectomy may yield short‐term benefits , but has not been investigated in a r and omized trial . The aim of this study was to compare laparoscopic and open pancreatoduodenectomy for short‐term outcomes in a r and omized trial", "Background : Forced-air warming is sometimes unable to maintain perioperative normothermia . Therefore , the authors compared heat transfer , regional heat distribution , and core rewarming of forced-air warming with a novel circulating-water garment . Methods : Nine volunteers were each evaluated on two r and omly ordered study days . They were anesthetized and cooled to a core temperature near 34 ° C . The volunteers were subsequently warmed for 2.5 h with either a circulating-water garment or a forced-air cover . Overall , heat balance was determined from the difference between cutaneous heat loss ( thermal flux transducers ) and metabolic heat production ( oxygen consumption ) . Average arm and leg ( peripheral ) tissue temperatures were determined from 18 intramuscular needle thermocouples , 15 skin thermal flux transducers , and “ deep ” h and and foot thermometers . Results : Heat production ( approximately 60 kcal/h ) and loss ( approximately 45 kcal/h ) were similar with each treatment before warming . The increases in heat transfer across anterior portions of the skin surface were similar with each warming system ( approximately 65 kcal/h ) . Forced-air warming had no effect on posterior heat transfer , whereas circulating-water transferred 21 ± 9 kcal/h through the posterior skin surface after a half hour of warming . Over 2.5 h , circulating water thus increased body heat content 56 % more than forced air . Core temperatures thus increased faster than with circulating water than forced air , especially during the first hour , with the result that core temperature was 1.1 ° ± 0.7 ° C greater after 2.5 h ( P increased twice as much as core heat content with each device , but the core-to-peripheral tissue temperature gradient remained positive throughout the study . Conclusions : The circulating-water system transferred more heat than forced air , with the difference result ing largely from posterior heating . Circulating water rewarmed patients 0.4 ° C/h faster than forced air . A substantial peripheral-to-core tissue temperature gradient with each device indicated that peripheral tissues insulated the core , thus slowing heat transfer", "Background Postoperative nausea and vomiting ( PONV ) is a common complication after surgery , which increases physical and psychological discomfort and delays recovery . The aim of this study was to test the hypothesis that ramosetron is comparable to ondansetron for the treatment of established PONV after laparoscopic surgery using a prospect i ve , r and omized , double-blinded , noninferiority study . Methods Patients who had at least two risk factors of PONV and underwent laparoscopic surgery under general anesthesia were assessed for eligibility . Patients who developed PONV within the first 2 h after anesthesia received ondansetron ( 4 mg ) or ramosetron ( 0.3 mg ) intravenously in a r and omized double-blind manner . Patients were then observed for 24 h after drug administration . The incidence of nausea and vomiting , severity of nausea , rescue antiemetic necessity , and adverse effects at 0–2 or 2–24 h after drug administration was evaluated . The primary endpoint was the rate of patients exhibiting a complete response , defined as no emesis and no further rescue antiemetic medication for 24 h after drug administration . Results Among the 583 patients , 210 ( 36.0 % ) developed PONV and were r and omized to either the ondansetron ( n=105 ) or ramosetron ( n=105 ) group . Patient ’s characteristics were similar between the groups . The complete response rate was 44.1 % in the ondansetron group and 52.9 % in the ramosetron group after 24 h of initial antiemetic administration . The incidence of adverse events was not different between the groups . Conclusion We found evidence to support the noninferiority of ramosetron ( 0.3 mg ) compared to ondansetron ( 4 mg ) for the treatment of established PONV in moderate to high-risk patients undergoing laparoscopic surgery", "Background Although bile contamination caused by preoperative biliary drainage ( PBD ) is a risk factor for infectious complications after pancreatoduodenectomy , the appropriate perioperative antibiotic regimen remains unclear . We evaluated a perioperative antibiotic strategy targeting bile contamination associated with PBD procedures for preventing abdominal infectious complications after pancreatoduodenectomy . Methods Consecutive patients ( n = 254 ) underwent pancreatoduodenectomy at a single center . Perioperative antibiotics were mainly cefazolin in non-PBD cases ( n = 116 ) and cefozopran in internal-PBD cases ( n = 87 ) . They were based on preoperative bile cultures in 51 of the external-PBD cases . Intraoperative bile cultures were examined prospect ively . Morbidity and abdominal infectious complication rates were evaluated . Results The incidence of positive intraoperative bile cultures was significantly higher in the internal-PBD ( 85 % ) and external-PBD ( 90 % ) cases than in the non-PBD cases ( 26 % ) ( p susceptibility to cefazolin for non-PBD was significantly higher than the 61 % for internal-PBD or 45 % for external-PBD ( p Overall morbidity rates ( 23 , 23 , and 25 % ) and abdominal infectious complications ( 13 , 17 , and 14 % ) did not differ among the non-PBD , internal-PBD , and external-PBD cases , respectively . Only susceptibility to perioperative antibiotics of biliary microorganisms classified as resistant was a significant independent risk factor for abdominal infectious complications ( p = 0.003 ) . Conclusions A perioperative antibiotic strategy particular to PBD procedures is valid for covering biliary microorganisms during pancreatoduodenectomy . Perioperative antibiotics covering bile contamination may prevent abdominal infectious complications after pancreatoduodenectomy in patients with and without PBD", "Background Preoperative weight loss and abnormal serum-albumin have traditionally been associated with reduced survival . More recently , a correlation between postoperative complications and reduced long-term survival has been reported and the significance of the relative proportion of skeletal muscle , visceral and subcutaneous adipose tissue has been examined with conflicting results . We investigated how preoperative body composition and major non-fatal complications related to overall survival and compared this to established predictors in a large cohort undergoing upper abdominal surgery . Methods From 2001 to 2006 , 447 patients were included in a Norwegian multicenter r and omized controlled trial in major upper abdominal surgery . Patients were now , six years later , analyzed as a single prospect i ve cohort and overall survival was retrieved from the National Population Registry . Body composition indices were calculated from CT images taken within three months preoperatively . Results Preoperative serum-albumin weight loss > 5 % ( HR = 1.38 , p = 0.023 ) were independently associated with reduced survival . There was no association between any of the preoperative body composition indices and reduced survival . Major postoperative complications were independently associated with reduced survival but only as long as patients who died within 90 days were included in the analysis . Conclusions Our study has confirmed the robust significance of the traditional indicators , preoperative serum-albumin and weight loss . The body composition indices did not prove beneficial as global indicators of poor prognosis in upper abdominal surgery . We found no association between non-fatal postoperative complications and long-term survival ", "BACKGROUND Clinical ly relevant postoperative pancreatic fistulas ( CR-POPF ) are serious inherent risks of pancreatic resection . Preoperative CR-POPF risk assessment is currently inadequate and rarely disqualifies patients who need resection . The best evaluation of risk occurs intraoperatively , and should guide fistula prevention and response measures thereafter . We sought to develop a risk prediction tool for CR-POPF that features intraoperative assessment and reveals associated clinical and economic significance . STUDY DESIGN Based on International Study Group of Pancreatic Fistula classification , recognized risk factors for CR-POPF ( small duct , soft pancreas , high-risk pathology , excessive blood loss ) were evaluated during pancreaticoduodenectomy . An optimal risk score range model , selected from 3 different constructs , was first derived ( n = 233 ) and then vali date d prospect ively ( n = 212 ) . Clinical and economic outcomes were evaluated across 4 ranges of scores ( negligible risk , 0 points ; low risk , 1 to 2 ; intermediate risk , 3 to 6 ; high risk , 7 to 10 ) . RESULTS Clinical ly relevant postoperative pancreatic fistulas occurred in 13 % of patients . The incidence was greatest with excessive blood loss . Duct size fistula rates that rose with even smaller ducts . These factors , together with soft pancreatic parenchyma and certain disease pathologies , afforded a highly predictive 10-point Fistula Risk Score . Risk scores strongly correlated with fistula development ( p CR-POPF , while fistulas occurred in all patients with scores of 9 or 10 . Other clinical and economic outcomes segregated by risk profile across the 4 risk strata . CONCLUSIONS A simple 10-point Fistula Risk Score derived during pancreaticoduodenectomy accurately predicts subsequent CR-POPF . It can be readily learned and broadly deployed . This prediction tool can help surgeons anticipate , identify , and manage this ominous complication from the outset", "Aim Surgical site infection ( SSI ) remains a common postoperative morbidity , particularly in colorectal resections , and poses a significant financial burden to the healthcare system . The omission of mechanical bowel preparation , as is performed in enhanced recovery after surgery programmes , appears to further increase the incidence . Various wound protection methods have been devised to reduce the incidence of SSIs . However , there are few r and omized controlled trials assessing their efficacy . The aim of this study is to investigate whether ALEXIS wound retractors with reinforced O‐rings are superior to conventional wound protection methods in preventing SSIs in colorectal resections", "OBJECTIVE The aim of this study was to evaluate whether a change in the routine feeding strategy applied after pancreatoduodenectomy ( PD ) from nasojejunal tube ( NJT ) feeding to early oral feeding improved clinical outcomes . METHODS An observational cohort study was performed in 102 consecutive patients undergoing PD . In period 1 ( n = 51 , historical controls ) , the routine postoperative feeding strategy was NJT feeding . This was changed to a protocol of early oral feeding with on-dem and NJT feeding in period 2 ( n = 51 , consecutive prospect i ve cohort ) . The primary outcome was time to resumption of adequate oral intake . RESULTS The baseline characteristics of study subjects in both periods were comparable . In period 1 , 98 % ( n = 50 ) of patients received NJT feeding , whereas in period 2 , 53 % ( n = 27 ) of patients did so [ for delayed gastric empting ( DGE ) ( n = 20 ) or preoperative malnutrition ( n = 7 ) ] . The time to resumption of adequate oral intake significantly decreased from 12 days in period 1 to 9 days in period 2 ( P = 0.015 ) , and the length of hospital stay shortened from 18 days in period 1 to 13 days in period 2 ( P = 0.015 ) . Overall , there were no differences in the incidences of complications of Clavien-Dindo Grade III or higher , DGE , pancreatic fistula , postoperative haemorrhage and mortality between the two periods . CONCLUSIONS The introduction of an early oral feeding strategy after PD reduced the time to resumption of adequate oral intake and length of hospital stay without negatively impacting postoperative morbidity", "BACKGROUND Falls are a common adverse event during hospitalization of older adults , and few interventions have been shown to prevent them . METHODS This study was a 3-group r and omized trial to evaluate the efficacy of 2 forms of multimedia patient education compared with usual care for the prevention of in-hospital falls . Older hospital patients ( n = 1206 ) admitted to a mixture of acute ( orthopedic , respiratory , and medical ) and subacute ( geriatric and neurorehabilitation ) hospital wards at 2 Australian hospitals were recruited between January 2008 and April 2009 . The interventions were a multimedia patient education program based on the health-belief model combined with trained health professional follow-up ( complete program ) , multi-media patient education material s alone ( material s only ) , and usual care ( control ) . Falls data were collected by blinded research assistants by review ing hospital incident reports , h and search ing medical records , and conducting weekly patient interviews . RESULTS Rates of falls per 1000 patient-days did not differ significantly between groups ( control , 9.27 ; material s only , 8.61 ; and complete program , 7.63 ) . However , there was a significant interaction between the intervention and presence of cognitive impairment . Falls were less frequent among cognitively intact patients in the complete program group ( 4.01 per 1000 patient-days ) than among cognitively intact patients in the material s-only group ( 8.18 per 1000 patient-days ) ( adjusted hazard ratio , 0.51 ; 95 % confidence interval , 0.28 - 0.93 ] ) and control group ( 8.72 per 1000 patient-days ) ( adjusted hazard ratio , 0.43 ; 95 % confidence interval , 0.24 - 0.78 ) . CONCLUSION Multimedia patient education with trained health professional follow-up reduced falls among patients with intact cognitive function admitted to a range of hospital wards . Trial Registration anzctr.org.au Identifier : ACTRN12608000015347", "We aim ed to evaluate perioperative outcomes in patients undergoing pancreaticoduodenectomy with or without a cardiac output goal directed therapy ( GDT ) algorithm . We conducted a multicentre r and omised controlled trial in four high volume hepatobiliary-pancreatic surgery centres . We evaluated whether the additional impact of a intraoperative fluid optimisation algorithm would influence the amount of fluid delivered , reduce fluid related complications , and improve length of hospital stay . Fifty-two consecutive adult patients were recruited . The median ( IQR ) duration of surgery was 8.6 hours ( 7.1:9.6 ) in the GDT group vs. 7.8 hours ( 6.8:9.0 ) in the usual care group ( p = 0.2 ) . Intraoperative fluid balance was 1005mL ( 475:1873 ) in the GDT group vs. 3300mL ( 2474:3874 ) in the usual care group ( p Total volume of fluid administered intraoperatively was also lower in the GDT group : 2050mL ( 1313:2700 ) vs. 4088mL ( 3400:4525 ) , p vasoactive medications were used more frequently . There were no significant differences in proportions of patients experiencing overall complications ( p = 0.179 ) ; however , fewer complications occurred in the GDT group : 44 vs. 92 ( Incidence Rate Ratio : 0.41 ; 95%CI 0.24 to 0.69 , p = 0.001 ) . Median ( IQR ) length of hospital stay was 9.5 days ( IQR : 7.0 , 14.3 ) in the GDT vs. 12.5 days in the usual care group ( IQR : 9.0 , 22.3 ) for an Incidence Rate Ratio 0.64 ( 95 % CI 0.48 to 0.85 , p = 0.002 ) . In conclusion , using a surgery-specific , patient-specific goal directed restrictive fluid therapy algorithm in this cohort of patients , can justify using enough fluid without causing oedema , yet as little fluid as possible without causing hypovolaemia i.e. “ precision ” fluid therapy . Our findings support the use of a perioperative haemodynamic optimization plan that prioritizes preservation of cardiac output and organ perfusion pressure by judicious use of fluid therapy , rational use of vasoactive drugs and timely application of inotropic drugs . They also suggest the need for further larger studies to confirm its findings", "BACKGROUND The high frequency of surgical site infections ( SSIs ) after hepato-pancreato-biliary ( HPB ) surgery is a problem that needs to be addressed . This prospect i ve , r and omized , controlled study examined whether perioperative prophylactic use of antibiotics based on preoperative bile culture results in HPB surgery could decrease SSI . METHODS Participants comprised 126 patients who underwent HPB ( bile duct , gallbladder , ampullary , or pancreatic ) cancer surgery with biliary reconstruction at Hokkaido University Hospital between August 2008 and March 2013 ( UMIN Clinical Trial Registry # 00001278 ) . Before surgery , subjects were r and omly allocated to a targeted group administered antibiotics based on bile culture results or a st and ard group administered cefmetazole . The primary endpoint was SSI rates within 30 days after surgery . Secondary endpoint was SSI rates for each operative procedure . RESULTS Of the 126 patients , 124 were r and omly allocated ( targeted group , n = 62 ; st and ard group , n = 62 ) . Frequency of SSI after surgery was significantly lower in the targeted group ( 27 patients , 43.5 % ) than in the st and ard group ( 44 patients , 71.0 % ; P = 0.002 ) . Among patients who underwent pancreaticoduodenectomy and hepatectomy , SSI occurred significantly less frequently in the targeted group ( P = 0.001 and P = 0.025 , respectively ) . CONCLUSIONS This study demonstrated that preoperative bile culture-targeted administration of prophylactic antibiotics decreased SSIs following HBP surgery with biliary reconstruction", "Background Perioperative fluid restriction in a variety of operations has shown improvement of : complications , recovery of gastrointestinal function and length of stay ( LOS ) . We investigated effects of crystalloid fluid restriction in pancreatic surgery . Our hypothesis : enhanced recovery of gastrointestinal function . Methods In this double-blinded r and omized trial , patients scheduled to undergo pancreatoduodenectomy ( PD ) were r and omized : st and ard ( S:10ml/kg/hr ) or restricted ( R:5ml/kg/hr ) fluid protocol s. Primary endpoint : gastric emptying scintigraphically assessed on postoperative day 7 . Results In 66 r and omized patients , complications and 6-year survival were analyzed . 54 patients were analyzed in intention to treat : 24 S-group and 30 R-group . 32 patients actually underwent a PD and 16 patients had a palliative gastrojejunostomy bypass operation in the full protocol analysis . The median gastric emptying time ( T½ ) was 104 minutes ( S-group , 95 % confidence interval : 74–369 ) versus 159 minutes ( R-group , 95 % confidence interval : 61–204 ) ( P = 0.893 , NS ) . Delayed gastric emptying occurred in 10 patients in the S-group and in 13 patients in the R-group ( 45 % and 50 % , P = 0.779 , NS ) . The primary outcome parameter , gastric emptying time , did not show a statistically significant difference between groups . Conclusion A fluid regimen of 10ml/kg/hr or 5ml/kg/hr during pancreatic surgery did not lead to statistically significant differences in gastric emptying . A larger study would be needed to draw definite conclusions about fluid restriction in pancreatic surgery . Trial registration IS RCT", "Objective : To determine whether an intervention with smoking cessation starting 4 weeks before general and orthopedic surgery would reduce the frequency of postoperative complications . Summary Background Data : Complications are a major concern after elective surgery and smokers have an increased risk . There is insufficient evidence concerning how the duration of preoperative smoking intervention affects postoperative complications . Methods : A r and omized controlled trial , conducted between February 2004 and December 2006 at 4 university-affiliated hospitals in the Stockholm region , Sweden . The outcome assessment was blinded . The follow-up period for the primary outcome was 30 days . Eligibility criteria were active daily smokers , aged 18 to 79 years . Of the 238 patients assessed , 76 refused participating , and 117 men and women undergoing surgery for primary hernia repair , laparoscopic cholecystectomy , or a hip or knee prosthesis were enrolled . Intervention : Smoking cessation therapy with individual counseling and nicotine substitution started 4 weeks before surgery and continued 4 weeks postoperatively . The control group received st and ard care . The main outcome measure was frequency of any postoperative complication . Results : An intention-to-treat analysis showed that the overall complication rate in the control group was 41 % , and in the intervention group , it was 21 % ( P = 0.03 ) . Relative risk reduction for the primary outcome of any postoperative complication was 49 % and number needed to treat was 5 ( 95 % CI , 3–40 ) . An analysis per protocol showed that abstainers had fewer complications ( 15 % ) than those who continued to smoke or only reduced smoking ( 35 % ) , although this difference was not statistically significant . Conclusion : Perioperative smoking cessation seems to be an effective tool to reduce postoperative complications even if it is introduced as late as 4 weeks before surgery", "Objective : A prospect i ve consecutive study was planned to evaluate the postpancreaticoduodenectomy ( PD ) oral intake tolerance . The occurrence of delayed gastric emptying ( DGE ) , as defined by the International Study Group of Pancreatic Surgery ( ISGPS ) , and the amount of dietary intake were analyzed . The risk factors for low oral intake tolerance were additionally determined . Summary Background Data : The causation of DGE after PD is still unclear . Several possible factors have been discussed , such as reconstruction methods and other complications . However , none of them has followed the definition of ISGPS . Methods : Between 2003 and 2007 , 101 consecutive patients underwent PD-related surgery , and st and ard operative procedure was performed on 85 patients . Perioperative data were prospect ively collected in all patients , and the patient 's postoperative dietary intake was recorded for all meals until discharge . As an indicator of early postoperative oral intake tolerance , we added up the dietary intake from postoperative day 1 to 21 and called this value the total amount of dietary intake ( TDI ) . The postoperative outcomes were compared between non-DGE and DGE . The high-low of TDI values was also analyzed . Multivariate analysis for factors associated with the occurrence of DGE and TDI was performed . Results : The occurrence of DGE as defined by ISGPS was 42 % . The postoperative outcomes of DGE patients were significantly poor compared with those of non-DGE patients . TDI values were significantly low in DGE patients , and non-DGE patients with low TDI values showed a significantly extended duration of parenteral nutrition and postoperative hospitalization . Operative bleeding ( > 1,000 mL ) and pancreatic fistulas were likely to be associated with DGE occurrence . Gender ( women ) , BMI ( > 25 kg/m2 ) , postoperative intraabdominal infection , and DGE were significantly associated with low TDI values . Conclusions : The ISGPS definition of DGE seemed feasible for patient management . TDI values provided additional information for analyzing postoperative oral intake tolerance , especially when describing the differences among non-DGE patients . Substantial risk factors for low oral intake tolerance were high BMI , postoperative intraabdominal infection , and DGE", "Objective : This study was design ed to determine whether the volume and type of fluid administered for pancreaticoduodenectomy impacts postoperative outcomes . Background : Three percent hypertonic saline ( HYS ) has been suggested as a means of reducing the volume of fluid required to sustain tissue perfusion in the perioperative period . Methods : Between May 2011 and November 2013 , patients undergoing pancreaticoduodenectomy were enrolled in an institutional review board – approved , single-center , prospect i ve , parallel , r and omized controlled trial ( NCT 01428050 ) , comparing lactated Ringers ( LAR ) ( 15 mL/kg/hr LAR intraoperation , 2 mL/kg/hr LAR postoperation ) with HYS ( 9 mL/kg/hr LAR and 1 mL/kg/hr HYS intraoperation , 1 mL/kg/hr HYS postoperation ) . Results : A total of 264 patients were r and omized . Demographic variables between groups were similar . The HYS patients had a significantly reduced net fluid balance ( 65 vs 91 mL/kg , P = 0.02 ) . The overall complication rate was reduced in the HYS group ( 43 % vs 54 % ) , with a relative risk of 0.79 [ 95 % confidence interval ( CI ) , 0.62–1.02 ; P = 0.073 ] , factoring stratification for pancreas texture . After adjustment for age and weight , the relative risk was 0.75 [ 95 % CI ( 0.58–0.96 ) ; P = 0.023 ] . The total number of complications was significantly reduced in the HYS group ( 93 vs 123 ) , with an incidence rate ratio of 0.74 [ 95 % CI ( 0.56–0.97 ) ; P = 0.027 ] . After adjustment for age and weight , the incidence rate ratio was 0.69 [ 95 % CI ( 0.52–0.90 ) ; P = 0.0068 ] . Reoperations , length of stay , readmissions , and 90-day mortality were similar between groups . Conclusions : A moderately restrictive fluid regimen with HYS result ed in a statistically significant 25 % reduction in complications when adjusted for age , weight , and pancreatic texture", "Background Surgical site infections ( SSI ) following pancreatoduodenectomy ( PD ) contribute to adverse perioperative and long-term outcomes . Hence , the need to determine the modifiable factors related to their causation . Aim To identify demographic , nutritional , surgical and histopathological factors significantly associated with incisional SSIs . Methods A retrospective analysis of a prospect ively maintained data base of consecutive patients who underwent PD for pancreatic and periampullary lesions at a tertiary care referral centre , between April 2010 and June 2014 was carried out . Patients were divided into two groups based on the SSIs ( Group 1—With SSI ; Group 2—No SSI ) . All patients were administered three , once daily doses of Ertapenem ( 1 g ) as follows : within 1 h prior to induction , and on day 1 and day 2 following surgery . No further antibiotics were given prior to discharge unless clinical ly indicated . Results 35 out of 277 patients ( 12.6 % ) developed SSIs . No demographic ( age , sex , BMI ) , nutritional ( serum albumin ) , surgical ( pancreatic duct size and texture , surgical duration and intraoperative blood transfusions ) and histopathological factors ( malignancy vs. benign ) were noted between the two groups . However , SSIs were significantly higher in patients with endocrine co-morbidities ( other than diabetes mellitus ) , in those patients who had undergone prior ERCP and stenting , as well as an end-to-side pancreaticojejunostomy . Patients with diabetes mellitus had a significantly lower incidence of wound infections ( P = .014 ) . Conclusion Preoperative ERCP and stenting , end-to-side PJ and the presence of non-diabetic endocrine co-morbidity may result in a significantly higher risk of SSIs . Further studies targeting these patient sub population s are warranted to enable a better underst and ing of how these factors contribute to the incidence of SSIs following PD", "Objective : To estimate the extent to which the addition of staff-directed facilitation of early mobilization to an Enhanced Recovery Program ( ERP ) impacts recovery after colorectal surgery , compared with usual care . Summary Background Data : Early mobilization is considered an important component of ERPs but , despite guidelines recommendations , adherence remains quite low . The value of dedicating specific re sources ( eg , staff time ) to increase early mobilization is unknown . Methods : This r and omized trial involved 99 colorectal surgery patients in an established ERP ( median age 63 , 57 % male , 80 % laparoscopic ) r and omized 1:1 to usual care ( including preoperative education about early mobilization with postoperative daily targets ) or facilitated mobilization [ staff dedicated to assist transfers and walking from postoperative days ( PODs ) 0–3 ] . Primary outcome was the proportion of patients returning to preoperative functional walking capacity ( 6-min walk test ) at 4 weeks after surgery . We also explored the association of the intervention with in-hospital mobilization , time to achieve discharge criteria , time to recover gastrointestinal function , 30-day comprehensive complication index , and patient-reported outcome measures . Results : In the facilitated mobilization group , adherence to mobilization targets was greater on POD0 [ OR 4.7 ( 95 % CI 1.8–11.9 ) ] , POD1 [ OR 6.5 ( 95 % CI 2.3–18.3 ) ] , and POD2 [ OR 3.7 ( 95 % CI 1.2–11.3 ) ] . Step count was at least 2-fold greater on POD1 [ mean difference 843.3 steps ( 95 % CI 219.5–1467.1 ) ] and POD2 [ mean difference 1099.4 steps ( 95 % CI 282.7–1916.1 ) ] There was no between-group difference in recovery of walking capacity at 4 weeks after surgery [ OR 0.77 ( 95 % CI 0.30–1.97 ) ] . Other outcome measures were also not different between groups . Conclusions : In an ERP for colorectal surgery , staff-directed facilitation of early mobilization increased out-of-bed activities during hospital stay but did not improve outcomes . This study does not support the value of allocating additional re sources to ensure early mobilization in ERPs . Trial Registration : Clinical Trials.gov Identifier :", "Postoperative insulin resistance is a well-characterized metabolic state that has been shown to correlate with the length of postoperative stay in hospital . Preoperative intravenous or oral carbohydrate treatment has been shown to attenuate the development of postoperative insulin resistance measured 1 day after surgery . To study the effects of preoperative oral carbohydrate treatment on postoperative changes in insulin resistance and substrate utilization , in the absence of postoperative confounding factors , 15 patients were double-blindly treated with either a carbohydrate-rich beverage ( 12.5 % ) ( n = 8) or placebo ( n = 7 ) before undergoing total hip replacement surgery . Insulin sensitivity , endogenous glucose release , and substrate oxidation rates were measured before and immediately after surgery . Whole body insulin sensitivity decreased by 18 % in the treatment group vs. 43 % in the placebo group ( P insulin-induced nonoxidative glucose disposal after surgery . The better preservation of insulin sensitivity in the treatment group was attributable to a less reduced glucose disposal in peripheral tissues and increased glucose oxidation rates", "The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience .", "Background Preoperative biliary drainage ( PBD ) is associated with bacterial contamination of bile , but the effects of PBD on morbidity after pancreatoduodenectomy remain controversial . The aim of this study was to characterize bile contamination to develop successful specific antibiotic prophylactic strategies for pancreatoduodenectomy . Methods Ninety-one consecutive patients who underwent pancreatoduodenectomy for periampullary tumor were prospect ively evaluated . Prophylactic antibiotics were selected based on preoperative bile cultures . Bile cultures and postoperative complications were compared in 46 patients who underwent PBD ( drainage group ) versus 45 patients who did not ( nondrainage group ) . Results The incidence of positive bile cultures was higher in the drainage group ( 78 % ) than in the nondrainage group ( 36 % ) ( P positive bile cultures were frequently polymicrobial ( 61 % ) and demonstrated resistance to several antibiotics , including cefazolin ( 83 % ) , cefmetazole ( 72 % ) , and cefpirome ( 64 % ) . Overall morbidity ( 30 % and 22 % ) and infectious morbidity ( 13 % and 11 % ) did not differ significantly between the drainage and nondrainage groups , respectively . Conclusions PBD had a notable influence on bile microbial contamination , including a higher rate of antibiotic resistance . Therefore , specific antibiotic prophylaxis based on bile culture is required for preventing infectious complications in pancreatoduodenectomy patients who undergo PBD ", "Purpose It has been reported that recently developed circulating-water garments transfer more heat than a forced-air warming system . The authors evaluated the hypothesis that circulating-water leg wraps combined with a water mattress better maintain intraoperative core temperature ≥36 ° C than either forced-air warming or carbon-fiber resistive heating during major abdominal surgery . Methods Thirty-six patients undergoing open abdominal surgery were r and omly assigned to warming with : ( 1 ) circulating-water leg wraps combined with a full-length circulating-water mattress set at 42 ° C , ( 2 ) a lower-body forced-air cover set on high ( ≈43 ° C ) , and ( 3 ) a carbon-fiber resistive-heating cover set at 42 ° C . Patients were anesthetized with general anesthesia combined with continuous epidural analgesia . The primary outcome was intraoperative tympanic-membrane temperature ≥36 ° C . Results In the 2 h after anesthesia induction , core temperature decreased 1.0 ± 0.5 ° C in the forced-air group , 0.9 ± 0.2 ° C in the carbon-fiber group , and 0.4 ± 0.4 ° C in the circulating-water leg wraps and mattress group ( P surgery , core temperature was 0.2 ± 0.7 ° C above preoperative values in the circulating-water group but remained 0.6 ± 0.9 ° C less in the forced-air and 0.6 ± 0.4 ° C less in the carbon-fiber groups ( P maintain intraoperative core temperature than did forced-air and carbon-fiber warming systems", "Background : Epidural anesthesia with local anesthetics is associated with postoperative attenuation of nitrogen loss . The protein‐sparing effect could be the result of either a decreased protein breakdown or increased protein synthesis . Although the role of epidural local anesthetics in effectively limiting the increase in postoperative protein breakdown is established at the whole‐body level , it is necessary to determine whether the muscle protein fractional synthetic rate is directly modulated when nociceptive stimuli are blocked . Methods : Twelve otherwise healthy patients scheduled for elective colorectal surgery , who were receiving a constant intake of nitrogen ( 0.1 g [ center dot ] kg sup ‐1 [ center dot ] day sup ‐1 ) and calories ( 20 kcal [ center dot ] kg sup ‐1 [ center dot ] day sup ‐1 ) before and after surgery , were r and omly assigned to receive either general anesthesia ( with thiopentone , vecuronium , fentanyl , or enflurane ; control group , n = 6 ) or epidural anesthesia ( T3‐S5 sensory block with 0.75 % bupivacaine ) and general anesthesia ( epidural group , n = 6 ) . In the control group , postoperative analgesia was achieved with papaveretum given subcutaneously , whereas a continuous epidural bupivacaine infusion ( T8‐L5 sensory block ) was maintained for 48 h in the epidural group . The postabsorptive muscle protein fractional synthetic rate was determined using a 6‐h continuous infusion of13 C‐labeled leucine ( 1 mg [ center dot ] kg sup ‐1 [ center dot ] h sup ‐1 ) , and the13 C enrichment in muscle biopsy specimens before surgery and 48 h after surgery was measured . Results : Plateau13 C enrichment of plasma alpha‐ketoisocaproate ( taken to represent the intracellular leucine precursor pool enrichment for protein synthesis ) was achieved during the 6‐h infusion ( mean coefficient of variation was 2.8 % ) . Muscle protein synthesis at 48 h after operation compared with preoperative levels decreased significantly in the control group ( P = 0.03 ) . In contrast , it increased by 25 % in the epidural group . Although this was not significantly ( P = 0.15 ) different from preoperative levels , it was significantly greater than in the control patients . Conclusions : Epidural infusion of local anesthetics begun before surgery and continued during the first 48 h after operation significantly attenuates the decrease in the postabsorptive muscle protein synthesis rate associated with surgical injury . Effective block of nociceptive stimuli thus preserves tissue protein synthesis", "Objective : To assess the impact of postoperative complications on the receipt of adjuvant chemotherapy . Background : R and omized trials have demonstrated that adjuvant chemotherapy is associated with improved long-term survival . However , pancreatic surgery is associated with significant morbidity and the degree to which complications limit subsequent treatment options is unknown . Methods : Patients from the American College of Surgeons National Surgical Quality Improvement Program and the National Cancer Data Base who underwent pancreatic resection for cancer were linked ( 2006–2009 ) . The associations between complications and adjuvant chemotherapy use or treatment delay ( ≥70 days from surgery ) were assessed using multivariable regression methods . Results : From 149 hospitals , 2047 patients underwent resection for stage I-III pancreatic adenocarcinoma of which 23.2 % had at least 1 serious complication . Overall adjuvant chemotherapy receipt was 57.7 % : 61.8 % among patients not experiencing any complication and 43.6 % among those who had a serious complication . Serious complications increased the likelihood of not receiving adjuvant therapy over twofold [ odds ratio ( OR ) = 2.20 , 95 % confidence interval ( CI ) : 1.73–2.80 ] . Specific complications associated with adjuvant chemotherapy omission were reintubation ( OR = 7.79 , 95 % CI : 3.59–16.87 ) , prolonged ventilation ( OR = 5.92 , 95 % CI : 3.23–10.86 ) , pneumonia ( OR = 2.83 , 95 % CI : 1.63–4.90 ) , sepsis/shock ( OR = 2.76 , 95 % CI : 2.02–3.76 ) , organ space/deep surgical site infection ( OR = 2.19 , 95 % CI : 1.53–3.13 ) , venous thromboembolism ( OR = 1.92 , 95 % CI : 1.08–3.43 ) , and urinary tract infection ( OR = 1.61 , 95 % CI : 1.02–2.54 ) . Serious complications also doubled the likelihood of delaying adjuvant treatment administration ( OR = 2.08 , 95 % CI : 1.42–3.05 ) . Sensitivity analysis in a younger , healthier patient cohort demonstrated similar associations . Conclusions : Postoperative complications are common following pancreatic surgery and are associated with adjuvant chemotherapy omission and treatment delays", "Objective : The aim of this study is to examine , by a prospect i ve r and omized controlled trial , the influence of liberal ( LIB ) vs restricted ( RES ) perioperative fluid administration on morbidity following pancreatectomy . Summary of Background Data : R and omized controlled trials in patients undergoing major intra-abdominal surgery have challenged the historical use of LIB fluid administration , suggesting that a more restricted regimen may be associated with fewer postoperative complications . Methods : Patients scheduled to undergo pancreatic resection were consented for r and omization to a LIB ( n = 164 ) or RES ( n = 166 ) perioperative fluid regimen . Sample size was design ed with 80 % power to decrease Grade 3 complications from 35 % to 21 % . Results : Between July 2009 and July 2015 , we r and omized 330 patients undergoing pancreaticoduodenectomy ( PD , n = 218 ) , central ( n = 16 ) , or distal pancreatectomy ( DP , n = 96 ) . Patients were equally distributed for all demographic and intraoperative characteristics . Intraoperatively , LIB patients received crystalloid 12 mL/kg/h and RES patients 6 mL/kg/h . Cumulative crystalloid given ( median , range , mL ) days 0 to 3 was LIB : 12,252 ( 6600 to 21,365 ) , RES 7808 ( 2700 to 16,274 ) P Sixty-day mortality was 2 of 330 ( 0.6 % ) . Median operative time for PD was 227 minutes ( 105 to 462 ) and DP 150 ( 44 to 323 ) . Grade 3 complications occurred in 20 % of LIB and 27 % of RES patients ( P = 0.6 ) . Median length of stay was 7 and 5 days for PD and DP , respectively , in both arms . Conclusions : In a high volume institution , major perioperative complications from pancreatic resection were not significantly influenced by fluid regimens that differed approximately 1.6-fold", "Objective To test the hypothesis that routine intraperitoneal drainage is not required after pancreatic resection . Summary Background Data The use of surgically placed intraperitoneal drains has been considered routine after pancreatic resection . Recent studies have suggested that for other major upper abdominal resections , routine postoperative drainage is not required and may be associated with an increased complication rate . Methods After informed consent , eligible patients with peripancreatic tumors were r and omized during surgery either to have no drains placed or to have closed suction drainage placed in a st and ardized fashion after pancreatic resection . Clinical , pathologic , and surgical details were recorded . Results One hundred seventy-nine patients were enrolled in the study , 90 women and 89 men . Mean age was 65.4 years ( range 23–87 ) . The pancreas was the tumor site in 142 ( 79 % ) patients , with the ampulla ( n = 24 ) , duodenum ( n = 10 ) , and distal common bile duct ( n = 3 ) accounting for the remainder . A pancreaticoduodenectomy was performed in 139 patients and a distal pancreatectomy in 40 cases . Eighty-eight patients were r and omized to have drains placed . Demographic , surgical , and pathologic details were similar between both groups . The overall 30-day death rate was 2 % ( n = 4 ) . A postoperative complication occurred during the initial admission in 107 patients ( 59 % ) . There was no significant difference in the number or type of complications between groups . In the drained group , 11 patients ( 12.5 % ) developed a pancreatic fistula . Patients with a drain were more likely to develop a significant intraabdominal abscess , collection , or fistula . Conclusion This r and omized prospect i ve clinical trial failed to show a reduction in the number of deaths or complications with the addition of surgical intraperitoneal closed suction drainage after pancreatic resection . The data suggest that the presence of drains failed to reduce either the need for interventional radiologic drainage or surgical exploration for intraabdominal sepsis . Based on these results , closed suction drainage should not be considered m and atory or st and ard after pancreatic resection", "Background Introduced more than 20 years ago , laparoscopic pancreatic surgery ( LAPS ) has not reached a uniform acceptance among HPB surgeons . As a result , there is no consensus regarding its use in patients with pancreatic neoplasms . This study , organized by the European Association for Endoscopic Surgery ( EAES ) , aim ed to develop consensus statements and clinical recommendations on the application of LAPS in these patients . Methods An international panel of experts was selected based on their clinical and scientific expertise in laparoscopic and open pancreatic surgery . Each panelist performed a critical appraisal of the literature and prepared evidence -based statements assessed by other panelists during Delphi process . The statements were further discussed during a one-day face-to-face meeting followed by the second round of Delphi . Modified statements were presented at the plenary session of the 24th International Congress of the EAES in Amsterdam and in a web-based survey . Results LAPS included laparoscopic distal pancreatectomy ( LDP ) , pancreatoduodenectomy ( LPD ) , enucleation , central pancreatectomy , and ultrasound . In general , LAPS was found to be safe , especially in experienced h and s , and also advantageous over an open approach in terms of intraoperative blood loss , postoperative recovery , and quality of life . Eighty-five percent or higher proportion of responders agreed with the majority ( 69.5 % ) of statements . However , the evidence is predominantly based on retrospective case – control studies and systematic review s of these studies , clearly affected by selection bias . Furthermore , no r and omized controlled trials ( RCTs ) have been published to date , although four RCTs are currently underway in Europe . Conclusions LAPS is currently in its development and exploration stages , as defined by the international IDEAL framework for surgical innovation . LDP is feasible and safe , performed in many centers , while LPD is limited to few centers . RCTs and registry studies are essential to proceed with the assessment of LAPS", "OBJECTIVE The optimal perioperative blood glucose range to improve surgical site infection ( SSI ) in surgical intensive care unit ( ICU ) patients remains unclear . We sought to determine whether the incidence of SSI is reduced by perioperative intensive insulin therapy ( IT ) . RESEARCH DESIGN AND METHODS Patients were r and omly assigned to receive perioperative intensive IT , with a target blood glucose range of 4.4–6.1 mmol/L , or intermediate IT , with a target blood glucose range of 7.7–10.0 mmol/L in the surgical ICU . We defined the primary end point as the incidence of SSI . RESULTS Study participants were r and omly assigned to glucose control with one of two target ranges : for 225 patients in the intermediate IT group or for 222 patients in the intensive IT group , respectively . No patients in either group became hypoglycemic ( rate of SSI after hepato-biliary-pancreatic surgery was 6.7 % . Patients in the intensive IT group , compared with the intermediate IT group , had fewer postoperative SSIs ( 9.8 % vs. 4.1 % , P = 0.028 ) and a lower incidence of postoperative pancreatic fistula after pancreatic resection ( P = 0.040 ) . The length of hospitalization required for patients in the intensive IT group was significantly shorter than that in the intermediate IT group ( P = 0.017 ) . CONCLUSIONS We found that intensive IT decreased the incidence of SSI among patients who underwent hepato-biliary-pancreatic surgery : a blood glucose target of 4.4 to 6.1 mmol/L result ed in lower rate of SSI than did a target of 7.7–10.0", "BACKGROUND Postoperative pancreatic fistula is a major contributor to complications and death associated with pancreatic resection . Pasireotide , a somatostatin analogue that has a longer half-life than octreotide and a broader binding profile , decreases pancreatic exocrine secretions and may prevent postoperative pancreatic fistula . METHODS We conducted a single-center , r and omized , double-blind trial of perioperative subcutaneous pasireotide in patients undergoing either pancreaticoduodenectomy or distal pancreatectomy . We r and omly assigned 300 patients to receive 900 μg of subcutaneous pasireotide ( 152 patients ) or placebo ( 148 patients ) twice daily beginning preoperatively on the morning of the operation and continuing for 7 days ( 14 doses ) . R and omization was stratified according to the type of resection and whether the pancreatic duct was dilated at the site of transection . The primary end point was the development of pancreatic fistula , leak , or abscess of grade 3 or higher ( i.e. , requiring drainage ) . RESULTS The primary end point occurred in 45 of the 300 patients ( 15 % ) . The rate of grade 3 or higher postoperative pancreatic fistula , leak , or abscess was significantly lower among patients who received pasireotide than among patients who received placebo ( 9 % vs. 21 % ; relative risk , 0.44 ; 95 % confidence interval [ CI ] , 0.24 to 0.78 ; P=0.006 ) . This finding was consistent among 220 patients who underwent pancreaticoduodenectomy ( 10 % vs. 21 % ; relative risk , 0.49 ; 95 % CI , 0.25 to 0.95 ) and 80 patients who underwent distal pancreatectomy ( 7 % vs. 23 % ; relative risk , 0.32 ; 95 % CI , 0.10 to 0.99 ) , as well as among 136 patients with a dilated pancreatic duct ( 2 % vs. 15 % ; relative risk , 0.11 ; 95 % CI , 0.02 to 0.60 ) and 164 patients with a nondilated pancreatic duct ( 15 % vs. 27 % ; relative risk , 0.55 ; 95 % CI , 0.29 to 1.01 ) . CONCLUSIONS Perioperative treatment with pasireotide decreased the rate of clinical ly significant postoperative pancreatic fistula , leak , or abscess . ( Funded by Novartis Pharmaceuticals ; Clinical Trials.gov number , NCT00994110 . )", "BACKGROUND A recent heat-balance study in volunteers suggested that greater efficacy of circulating-water garments ( CWGs ) results largely from increased heat transfer across the posterior skin surface since heat transfer across the anterior skin surface was similar with circulating-water and forced-air . We thus tested the hypothesis that the combination of a circulating-water mattress ( CWM ) and forced-air warming prevents core temperature reduction during major abdominal surgery no worse than a CWG does . METHODS Fifty adult patients aged between 18 and 85 yr old , undergoing major abdominal surgery , were r and omly assigned to intraoperative warming with a combination of forced-air and a CWM or with a CWG ( Allon ThermoWrap ) . Core temperature was measured in the distal oesophagus . Non-inferiority of the CWM to the CWG on change from baseline to median intraoperative temperature was assessed using a one-tailed Student 's t-test with an equivalency buffer of -0.5 ° C . RESULTS Data analysis was restricted to 16 CWG and 20 CWM patients who completed the protocol . Core temperature increased in both groups during the initial hours of surgery . We had sufficient evidence ( P=0.001 ) , to conclude that the combination of a CWM and forced-air warming was non-inferior to a CWG in preventing temperature reduction , with mean ( 95 % CI ) difference in the temperature change between the CWM and the CWG groups ( CWM-CWG ) of 0.46 ° C ( -0.09 ° C , 1.00 ° C ) . CONCLUSIONS The combination of a CWM and forced-air warming is significantly non-inferior in maintaining intraoperative core temperature than a CWG . TRIAL REGISTRY This trial has been registered at clinical trials.gov , identifier : NCT 00651898", "BACKGROUND The preoperative visit is an appropriate time to educate the patient on anaesthesia . The aim of this study was to determine if a website , as an information source for anaesthesia before the visit to the preoperative assessment clinic ( PAC ) , increases patients ' knowledge on anaesthesia . METHODS A multimedia website was developed containing specific information about anaesthesia relevant to the patient . A question naire was developed to measure knowledge gain . Patients were divided into three groups : ( i ) those who read the existing brochure ; ( ii ) those who looked at the new website ; and ( iii ) a cluster of non-brochure and non-website users : those who did not read the brochure or website but had completed the question naire . An anaesthesiologist also informed all three groups during the preoperative visit at the PAC . RESULTS Patients visiting the website had a higher educational level than others . A significant increase in knowledge was observed after using the website information compared with the other two groups ( P knowledge gains , and the website independently contributed to the knowledge gain . CONCLUSIONS A patient-tailored multimedia website is an effective way to support the information provided by the anaesthesiologist in order to inform patients about their upcoming anaesthetic procedure . The use of such a website gives a significant increase in knowledge compared with only spoken information , or spoken information combined with a brochure", "AIM To characterize incidence and risk factors for delayed gastric emptying ( DGE ) following pancreaticoduodenectomy and examine its implication s on healthcare utilization . METHODS A prospect ively-maintained data base was review ed . DGE was classified using International Study Group of Pancreatic Surgery criteria . Patients who developed DGE and those who did not were compared . RESULTS Two hundred and seventy-six patients underwent pancreaticoduodenectomy ( PD ) ( > 80 % pylorus-preserving , antecolic-reconstruction ) . DGE developed in 49 patients ( 17.8 % ) : 5.1 % grade B , 3.6 % grade C. Demographic , clinical , and operative variables were similar between patients with DGE and those without . DGE patients were more likely to present multiple complications ( 32.6 % vs 4.4 % , ≥ 3 complications , P including postoperative pancreatic fistula ( POPF ) ( 42.9 % vs 18.9 % , P = 0.001 ) and intra-abdominal abscess ( IAA ) ( 16.3 % vs 4.0 % , P = 0.012 ) . Patients with DGE had longer hospital stay ( median , 12 d vs 7 d , P transitional care upon discharge ( 24.5 % vs 6.6 % , P after PD , it was associated with increased healthcare utilization . Patients with POPF and IAA were at risk for DGE . Anticipating DGE can help individualize care and allocate re sources to high-risk patients", "Background s/ Aims Major hepato-pancreato-biliary ( HPB ) surgery is usually performed via an open method rather than a laparoscopic method . Postoperative ileus ( POI ) is a classic complication after open surgery . The purpose of this study was to determine whether polylactic film is useful in the prevention of POI . Methods A total of 179 patients who underwent major HPB surgery between 2005 and 2014 , were retrospectively review ed . A diagnosis of POI was made by a physical examination , laboratory , and radiological findings . Surgi-Wrap ® polylactic film was preferentially used intraperitoneally by surgeons , just before wound closure . Results Major HPB surgery included pancreatoduodenectomy ( n=48 ) , distal or subtotal pancreatectomy ( n=24 ) , hepatectomy ( n=67 ) , other bile duct or gallbladder operations ( n=35 ) , and others ( n=5 ) . Although patients with polylactic film showed a significantly lower incidence of POI ( n=3 , 4.1 % vs. n=14 , 13.3 % , p=0.041 ) , they showed a significantly higher complication rate ( n=20 , 27.0 % vs. n=19 , 18.1 % , p=0.004 ) , particularly intra-abdominal fluid collection ( n=7 , 9.4 % vs. n=2 , 1.9 % ) , and wound infections ( n=6 , 8.1 % vs. n=3 , 2.9 % ) , than those who did not receive the film , respectively . Conclusions Although the polylactic film prevented POI , more complications other than POI were observed . Well- design ed r and omized controlled trials , using this anti-adhesive product , are needed to evaluate its effect on POI after major HPB surgery", "Although opioid-induced nausea and vomiting ( OINV ) is common and debilitating , its mechanism is still unclear . Recently , we suggested that opioids affect semicircular canal function and that this leads to a mismatch between canal input and other sensory information during head motion , which triggers OINV . Here , we assess if visual input is relevant for this mismatch . In a r and omized-controlled crossover study 14 healthy men ( 26.9±3.4 years , mean±SD ) were tested twice , once blindfolded and once with eyes open , with at least one-day washout . The opioid remifentanil was administered intravenously ( 0.15 μg/kg/min ) for 60 minutes . After a thirty-minutes resting period , subjects ’ head and trunk were passively moved . Nausea was rated before remifentanil start ( T0 ) , before the movement intervention ( T30 ) and after 60 minutes ( T60 ) of administration . At rest ( T0 , T30 ) , median nausea ratings were zero whether subjects were blindfolded or not . Movement triggered nausea independently of visual input ( nausea rating 1.5/3.0 ( median/interquartile range ) in the blindfolded , 2.5/6 in the eyes-open condition , χ2(1 ) = 1.3 , p = 0.25 ) . As movement exacerbates OINV independently of visual input , a clash between visual and semicircular canal information is not the relevant trigger for OINV . To prevent OINV , emphasis should be put on head-rest , eye-closure is less important", "HYPOTHESIS Use of prophylactic antibiotics in elective colorectal surgery is essential . Although single-dose prophylactic antibiotics are recommended , the efficacy of single-dose cephalosporin without metronidazole and oral antibiotics is not fully proven . We conducted a multicenter , r and omized trial of a single dose vs 3 doses of the second-generation cephalosporin cefmetazole . DESIGN A prospect i ve , r and omized , multicenter trial in patients undergoing elective colorectal surgery . SETTING Seven major hospitals in Japan that offer cancer treatment . PATIENTS Patients with colorectal cancer treated from May 6 , 2004 , to April 25 , 2005 . INTERVENTIONS Patients were r and omized to 1 of 2 groups : a single-dose group given a single dose of cefmetazole just before skin incision and a 3-dose group given 2 additional doses of cefmetazole every 8 hours after the first dose just before skin incision . MAIN OUTCOME MEASURES Incidences of incisional surgical site infection ( SSI ) , organ or space SSI , and all other infectious complications within 30 days after surgery . RESULTS A total of 384 patients were enrolled . Seven patients were excluded because of additional surgery or the inability to tolerate mechanical preparation . The incidence of incisional SSI was higher in the single-dose group ( 27/190 or 14.2 % ) than in the 3-dose group ( 8/187 or 4.3 % ) ( P = .009 ) . Incidences of organ or space SSI and other postoperative infectious diseases did not differ significantly between the 2 groups . In multivariate analysis , antibiotic dose was the only significant factor related to the incidence of incisional SSI . CONCLUSION Three-dose cefmetazole administration is significantly more effective for prevention of incisional SSI than single-dose antibiotic administration . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00292708", "Background Despite substantial improvements in surgical and anesthesiological practice s leading to decreased mortality of less than 5 % at high-volume centers , pancreatic surgery is still associated with high morbidity rates of up to 50 % . Attention is increasingly directed toward the optimization of perioperative management to reduce complications and enhance postoperative recovery . Currently , two different strategies for postoperative pain management after pancreatoduodenectomy are being routinely used : patient-controlled intravenous analgesia and thoracic epidural analgesia . Evidence is lacking to assess which strategy entails fewer postoperative complications . Methods / design The PAKMAN trial is design ed as an adaptive , pragmatic , r and omized , controlled , multicenter , open-label , superiority trial with two parallel study groups . A total of 370 patients scheduled for elective pancreatoduodenectomy will be r and omized after giving written informed consent , and 278 patients are needed for analysis . Patients with chronic pancreatitis , severe chronic obstructive pulmonary disease ( COPD ) , American Society of Anesthesiologists ( ASA ) physical status classification ≥ IV , or chronic pain syndrome will be excluded . The group A intervention includes intraoperative general anesthesia and postoperative patient-controlled intravenous analgesia ; the group B intervention comprises combined intraoperative general anesthesia and epidural analgesia with postoperative epidural analgesia . The primary endpoint of this trial is a composite of the gastrointestinal complications ( delayed gastric emptying , pancreatic fistula , biliary leak , gastrointestinal bleeding , and postoperative ileus ) up to postoperative day 30 . The aim is to investigate whether the frequency of gastrointestinal complications following pancreatoduodenectomy can be reduced by 15 % using postoperative , patient-controlled intravenous analgesia compared with epidural analgesia . Discussion Several previous studies investigating the two different strategies for postoperative pain management have mainly focused on their effectiveness in pain control . However , the PAKMAN trial is the first to compare them with regard to their impact on the surgical endpoint “ postoperative gastrointestinal complications ” after pancreatoduodenectomy . Trial registration German Clinical Trials Register ,", "BACKGROUND Epidural analgesia is the international st and ard for pain treatment in abdominal surgery . Although some studies have advocated continuous wound infiltration with local anaesthetics , robust evidence is lacking , especially on patient-reported outcome measures . We aim ed to determine the effectiveness of continuous wound infiltration in hepato-pancreato-biliary surgery . METHODS In this r and omised controlled , open label , non-inferiority trial ( POP-UP ) , we enrolled adult patients undergoing hepato-pancreato-biliary surgery by subcostal or midline laparotomy in two Dutch hospitals . Patients were central ly r and omised ( 1:1 ) to receive either pain treatment with continuous wound infiltration using bupivacaine plus patient-controlled analgesia with morphine or to receive ( patient-controlled ) epidural analgesia with bupivacaine and sufentanil . All patients were treated within an enhanced recovery setting . R and omisation was stratified by centre and type of incision . The primary outcome was the mean Overall Benefit of Analgesic Score ( OBAS ) from day 1 - 5 , a vali date d composite endpoint of pain scores , opioid side-effects , and patient satisfaction ( range 0 [ best ] to 28 [ worst ] ) . Analysis was per- protocol . The non-inferiority limit of the mean difference was + 3·0 . This trial is registered with the Netherl and s Trial Registry , number NTR4948 . FINDINGS Between Jan 20 , 2015 , and Sept 16 , 2015 , we r and omly assigned 105 eligible patients : 53 to receive continuous wound infiltration and 52 to receive epidural analgesia . One patient in the continuous wound infiltration group discontinued treatment , as did five in the epidural analgesia group ; of these five patients , preoperative placement failed in three ( these patients were treated with continuous wound infiltration instead ) , one patient refused an epidural , and data for the primary endpoint was lost for one . Thus , 55 patients were included in the continuous wound infiltration group and 47 in the epidural analgesia group for the per- protocol analyses . Mean OBAS was 3·8 ( SD 2·4 ) in the continuous wound infiltration group versus 4·4 ( 2·2 ) in the epidural group ( mean difference -0·62 , 95 % CI -1·54 to 0·30 ) . Because the upper bound of the one-sided 95 % CI did not exceed + 3·0 , non-inferiority was shown . Four ( 7 % ) patients in the continuous wound infiltration group and five ( 11 % ) of those in the epidural group had an adverse event . One patient in the continuous wound infiltration group had a serious adverse event ( temporary hypotension and arrhythmia after bolus injection ) ; no serious adverse events were noted in the epidural group . INTERPRETATION These data suggest that continuous wound infiltration is non-inferior to epidural analgesia in hepato-pancreato-biliary surgery within an enhanced recovery setting . Further large-scale trials are required to make a definitive assessment of non-inferiority . FUNDING Academic Medical Centre , Amsterdam , Netherl and", "ATIENTS undergoing major surgery encounter stereotypical alterations in carbohydrate and protein metabolism often referred to as the catabolic response . Characteristic features of impaired carbohydrate homeostasis are increased production of glucose combined with decreased glucose utilization result ing in hyperglycemia . The magnitude of hyperglycemia depends on the severity of surgical tissue trauma . In fasting non-diabetic patients undergoing elective intra-abdominal operations , blood glucose levels increase to 7–10 mmol·L –1 . During cardiac surgery , blood glucose values frequently exceed 15 mmol·L –1 in non-diabetic patients and 20 mmol·L –1 in diabetic subjects . Protein catabolism is characterized by a net loss of body protein . In metabolically healthy patients cumulative nitrogen losses , after elective abdominal operations , range between 40 and 80 g , equivalent to 1.2 to 2.4 kg lean tissue . Postoperative protein loss in patients with type 2 diabetes is 50 % greater than in their non-diabetic counterparts . 1 Much of the catabolic profile can be explained by specific neuroendocrine changes , including increased circulating concentrations of cortisol , glucagon , and catecholamines . These hormones exert catabolic effects , either directly or indirectly , by inhibiting insulin secretion and /or counteracting its peripheral action leading to the impairment of tissue insulin sensitivity . The extent of insulin resistance depends on the intensity of trauma , suggesting that insulin resistance is a marker of surgical stress . Clinical significance of the catabolic response to surgery Evidence is mounting that even moderate increases in blood glucose are associated with adverse outcomes . Patients with fasting glucose levels > 7 mmol·L –1 or r and om blood glucose levels > 11.1 mmol·L –1 on general surgical wards showed an 18-fold increase in in-hospital mortality , a longer length of stay , and a greater risk of infection . 2 In critically ill patients , mortality was directly correlated with increasing glucose levels above 5 mmol·L –1 . 3 In patients undergoing cardiovascular procedures , hyperglycemia was associated with increased mortality and organ dysfunction . 4 Furthermore , detrimental effects of acute hyperglycemia were documented in patients with cerebrovascular disease , myocardial ischemia , and trauma . Erosion of lean tissue protein delays wound healing , compromises immune function , and diminishes muscle strength after surgery . The result ing muscle weakness prolongs mechanical ventilation , inhibits effective coughing , and impedes mobilization . The length of time for return of normal physiologic function after discharge from the hospital is related to the extent of loss of lean body mass during hospitalization .", "BACKGROUND Smokers are at higher risk of cardiopulmonary and wound-related postoperative complications than non-smokers . Our aim was to investigate the effect of preoperative smoking intervention on the frequency of postoperative complications in patients undergoing hip and knee replacement . METHODS We did a r and omised trial in three hospitals in Denmark . 120 patients were r and omly assigned 6 - 8 weeks before scheduled surgery to either the control ( n=60 ) or smoking intervention ( 60 ) group . Smoking intervention was counselling and nicotine replacement therapy , and either smoking cessation or at least 50 % smoking reduction . An assessor , who was masked to the intervention , registered the occurrence of cardiopulmonary , renal , neurological , or surgical complications and duration of hospital admittance . The main analysis was by intention to treat . FINDINGS Eight controls and four patients from the intervention group were excluded from the final analysis because their operations were either postponed or cancelled . Thus , 52 and 56 patients , respectively , were analysed for outcome . The overall complication rate was 18 % in the smoking intervention group and 52 % in controls ( p=0.0003 ) . The most significant effects of intervention were seen for wound-related complications ( 5 % vs 31 % , p=0.001 ) , cardiovascular complications ( 0 % vs 10 % , p=0.08 ) , and secondary surgery ( 4 % vs 15 % , p=0.07 ) . The median length of stay was 11 days ( range 7 - 55 ) in the intervention group and 13 days ( 8 - 65 ) in the control group . INTERPRETATION An effective smoking intervention programme 6 - 8 weeks before surgery reduces postoperative morbidity , and we recommend , on the basis of our results , this programme be adopted", "Background Enteral immunodiet has been gaining increasing attention , but experimental data of its clinical effects in patients with gastric cancer are inconsistent , contradictory , and poorly investigated . The aim of this study was to assess the impact of early postoperative enteral immunonutrition on clinical and immunological outcomes in a homogeneous group of gastric cancer patients su bmi tted to total gastrectomy . Methods A total of 109 patients with gastric cancer were r and omized to receive early postoperative enteral immunonutrition ( formula supplemented with arginine , omega-3 fatty acids and ribonucleic acid [ RNA ] ) , or an isocaloric – isonitrogenous control . The postoperative outcome was evaluated based on clinical variables , including postoperative infectious complications , anastomotic leak rate , and length of hospitalization . In addition , state of cellular immunity was evaluated and compared between the 2 groups . Results The incidence of postoperative infectious complications in the immunodiet group ( 7.4 % ) was significantly ( p the anastomotic leak rate ( 3.7 % in immunodiet group vs 7.3 % in st and ard nutrition group , p did not show any significant differences ; patients of the immunodiet group were found to have a significantly reduced length of hospitalization ( 12.7 ± 2.3 days ) when compared with st and ard diet group ( 15.9 ± 3.4 days , p = .029 ) . The data on cellular immunity showed that the postoperative CD4 + T-cell counts decreased in both groups , but the reduction in the IED group was significantly higher ( p = .032 ) compared with the SND group . Conclusions Early postoperative enteral immunonutrition significantly improves clinical and immunological outcomes in patients undergoing gastrectomy for gastric cancer", "OBJECTIVE To evaluate the effect of intraoperative combined forced-air warming and fluid warming system on patient 's core temperature , blood loss , transfusion dem and , extubation time , and incidence of postoperative shivering . METHODS Forty patients with American Society of Anesthesiologists physical status I and II , aged 18 - 70 years , scheduled for elective abdominal surgery were r and omly assigned to receive intraoperative warming from a forced-air blanket and fluid warming system or conventional cotton blanket , 20 in each group . The core temperature was recorded every 20 minutes during the operation , as well as the blood loss , blood transfusion , extubation time , and incidence of postoperative shivering . RESULTS The core temperature at the end of the surgery in the warming group was significantly different from that in the control group ( 36.4 + /- 0.4 degrees C vs. 35.3 + /- 0.5 degrees C , P time between the end of the surgery and extubation ( P Postoperative shivering occurred in 30 % of the patients in the control group compared to no patient in the warming group ( P warming with air-forced blanket and fluid warming system provides sufficient heat to prevent hypothermia during abdominal surgery", "PURPOSE Adjuvant chemotherapy improves patient survival rates after resection for pancreatic adenocarcinoma , but the optimal duration and time to initiate chemotherapy is unknown . PATIENTS AND METHODS Patients with pancreatic ductal adenocarcinoma treated within the international , phase III , European Study Group for Pancreatic Cancer-3 ( version 2 ) study were included if they had been r and omly assigned to chemotherapy . Overall survival analysis was performed on an intention-to-treat basis , retaining patients in their r and omized groups , and adjusting the overall treatment effect by known prognostic variables as well as the start time of chemotherapy . RESULTS There were 985 patients , of whom 486 ( 49 % ) received gemcitabine and 499 ( 51 % ) received fluorouracil ; 675 patients ( 68 % ) completed all six cycles of chemotherapy ( full course ) and 293 patients ( 30 % ) completed one to five cycles . Lymph node involvement , resection margins status , tumor differentiation , and completion of therapy were all shown by multivariable Cox regression to be independent survival factors . Overall survival favored patients who completed the full six courses of treatment versus those who did not ( hazard ratio [ HR ] , 0.516 ; 95 % CI , 0.443 to 0.601 ; P Time to starting chemotherapy did not influence overall survival rates for the full study population ( HR , 0.985 ; 95 % CI , 0.956 to 1.015 ) . Chemotherapy start time was an important survival factor only for the subgroup of patients who did not complete therapy , in favor of later treatment ( P adjuvant chemotherapy rather than early initiation was an independent prognostic factor after resection for pancreatic adenocarcinoma . There seems to be no difference in outcome if chemotherapy is delayed up to 12 weeks , thus allowing adequate time for postoperative recovery", "BACKGROUND Pancreaticoduodenectomy remains a major undertaking with substantial perioperative morbidity and mortality . Previous studies in the colorectal population have noted a correlation between excessive postoperative fluid resuscitation and anastomotic complications . This study sought to assess the relationship between perioperative fluid management and clinical outcomes in patients undergoing pancreaticoduodenectomy . METHODS Data from a single institution , prospect i ve data base over a 10-year period ( 2002 to 2012 ) were review ed . Patients were compared for perioperative fluid balance and postoperative outcomes . Multivariable analysis was performed to assess the relationship between perioperative fluid administration and incidence of major adverse events . RESULTS Higher positive fluid balance on postoperative day 0 , postoperative day 1 , and postoperative day 2 was associated with increased incidence of major adverse events , increased postoperative intensive care unit admission , and longer hospital stay . Higher positive fluid balance on postoperative day 0 was most strongly associated with postoperative morbidity ( odds ratio 1.39 , confidence interval 1.16 to 1.66 , P = .0003 ) . Fluid balance on postoperative day 3 was not associated with adverse events . CONCLUSIONS Increased early perioperative fluid resuscitation is associated with major adverse events in patients undergoing pancreaticoduodenectomy . More restrictive fluid administration may improve postoperative outcomes ; further prospect i ve clinical trials focused on fluid resuscitation and goal -directed therapy are needed", "Objective : This multicenter study sought to prospect ively evaluate a drain management protocol for pancreatoduodenectomy ( PD ) . Background : Recent evidence suggests value for both selective drain placement and early drain removal for PD . Both strategies have been associated with reduced rates of clinical ly relevant pancreatic fistula (CR-POPF)—the most common and morbid complication after PD . Methods : The protocol was applied to 260 consecutive PDs performed at two institutions over 17 months . Risk for ISGPF CR-POPF was determined intraoperatively using the Fistula Risk Score ( FRS ) ; drains were omitted in negligible/low risk patients and drain fluid amylase ( DFA ) was measured on postoperative day 1 ( POD 1 ) for moderate/high risk patients . Drains were removed early ( POD 3 ) in patients with POD 1 DFA ⩽5,000 U/L , whereas patients with POD 1 DFA > 5,000 U/L were managed by clinical discretion . Outcomes were compared with a historical cohort ( N = 557 ; 2011–2014 ) . Results : Fistula risk did not differ between cohorts ( median FRS : 4 vs 4 ; P = 0.933 ) . No CR-POPFs developed in the 70 ( 26.9 % ) negligible/low risk patients . Overall CR-POPF rates were significantly lower after protocol implementation ( 11.2 vs 20.6 % , P = 0.001 ) . The protocol cohort also demonstrated lower rates of severe complication , any complication , reoperation , and percutaneous drainage ( all P experienced reduced hospital stay ( median : 8 days vs 9 days , P = 0.001 ) . There were no differences between cohorts in the frequency of bile or chyle leaks . Conclusions : Drains can be safely omitted for one-quarter of PDs . Drain amylase analysis identifies which moderate/high risk patients benefit from early drain removal . This data -driven , risk-stratified approach significantly decreases the occurrence of clinical ly relevant pancreatic fistula", "BACKGROUND / AIM Hypothermia in surgical patients can be the consequence of long duration of surgical intervention , general anaesthesia and low temperature in operating room . Postoperative hypothermia contributes to a number of postoperative complications such as arrhythmia , myocardial ischemia , hypertension , bleeding , wound infection , coagulopathy , and prolonged effect of muscle relaxants . External heating procedures are used to prevent this condition . The aim of this study was to evaluate the efficiency of external warming system in alleviation of cold stress and hypothermia in patients who underwent major surgical procedures . METHODS The study was conducted in the Military Medical Academy in Bel grade . A total of 30 patients of both genders underwent abdominal surgical procedures , r and omly divided into two equal groups : the one was externally warmed using warm air mattress ( W ) , while in the control group ( C ) surgical procedure was performed in regular conditions , without additional warming . Oesophageal temperature ( Te ) was used as indicator of changes in core temperature , during surgery and awakening postoperative period , and temperature of control sites on the right h and ( Th ) and the right foot ( Tf ) reflected the changes in skin temperatures during surgery . Te and skin temperatures were monitored during the intraoperative period , with continuous measurement of Te during the following 90 minutes of the postoperative period . Heart rates and blood pressures were monitored continuously during the intraoperative and awakening period . RESULTS In the W group , the average Te , Tf and Th did not change significantly during the intraoperative as well as the postoperative period . In the controls , the average Te significantly decreased during the intraoperative period ( from 35.61 ± 0.35 ° C at 0 minute to 33.86 ± 0.51 ° C at 120th minute ) . Compared to the W group , Te in the C group was significantly lower in all the observed periods . Average values of Tf and Th significantly decreased in the C group ( from 30.83 ± 1.85 at 20th minute to 29.0 ± 1.39 ° C at 120th minute , and from 32.75 ± 0.96 to 31.05 ± 1.09 ° C , respectively ) . CONCLUSION The obtained results confirm that the external warming using warm air mattress was able to attenuate hypothermia , i.e. substantial decrease in core temperature , compared with the similar exposure to cold stress in the control group", "Background The usefulness of enteral nutrition via a nasointestinal tube for patients who develop postoperative pancreatic fistula ( POPF ) after miscellaneous pancreatectomy procedures has been reported . However , no clear evidence regarding whether oral intake is possible during management of POPF after pancreatoduodenectomy ( PD ) is currently available . We investigated the effects of oral food intake on the healing process of POPF after PD by a multi-institutional r and omized controlled trial . Methods Patients who developed POPF were r and omly assigned to the dietary intake ( DI ) group ( n = 30 ) or the fasted group [ no dietary intake ( NDI ) group ] ( n = 29 ) . The primary endpoint was the length of drain placement . Results No significant differences were found in the length of drain placement between the DI and NDI groups [ 27 ( 7–80 ) vs. 26 ( 7–70 ) days , respectively ; p = .8858 ] . POPF progressed to a clinical ly relevant status ( grade B/C ) in 20 patients in the DI group and 19 patients in the NDI group ( p = .9257 ) . POPF-related intra-abdominal hemorrhage was found in 2 patients in the NDI group , but in no patients in the DI group ( p = .1434 ) . There were no significant differences in POPF-related intra-abdominal hemorrhage , the incidence of other complications , or the length of the postoperative hospital stay between the 2 groups . Conclusion Food intake did not aggravate POPF and did not prolong the length of drain placement or hospital stay after PD . There may be no need to avoid oral dietary intake in patients with POPF", "BACKGROUND The uptake of ω-3 polyunsaturated fatty acids ( PUFAs ) into the liver , gut mucosa , and tumor tissue and plasma levels after preoperative administration of supplemented enteral nutrition was investigated in patients with malignancies of the upper gastrointestinal tract . The objective of the study was to evaluate the incorporation of preoperatively administrated PUFAs , eicosapentaenoic acid ( EPA ) , and docosahexaenoic acid ( DHA ) into cell phospholipids . METHODS Patients undergoing major gastrointestinal surgery ( n = 40 ) were prospect ively r and omized to receive a PUFA-supplemented liquid oral diet 5 days preoperatively or an isocaloric control diet . The planned diet intake was 1000 mL/d providing 3.7 g of PUFA . The diet was given in addition to the usual hospital diet . The phospholipid fractions in plasma were analyzed on the day of surgery . Tissue sample s of liver , gut mucosa ( small intestine ) , and tumor were taken during surgery and homogenized . EPA and DHA content was analyzed using liquid gas chromatography . RESULTS Both patient groups ( PUFA group : n = 20 ; control group : n = 20 ) were similar in age , weight , and surgical procedures . As compared with the control group , the PUFA group had significantly increased levels of EPA in liver tissue ( 0.4 vs 1.3 weight % ) , gut mucosa ( 0.3 vs 1.0 weight % ) , and tumor tissue ( 0.3 vs 0.8 weight % ) . Also , the DHA levels in the PUFA group were significantly higher than the control group : liver tissue ( 4.1 vs 7.5 weight % ) , gut mucosa ( 2.1 vs 3.7 weight % ) and tumor tissue ( 1.9 vs 4.2 weight % ) . CONCLUSIONS This study suggests that administration of PUFA-enriched diets leads to increased incorporation of EPA and DHA not only in liver and gut mucosa tissue , but also in tumor tissue in patients with solid gastrointestinal tumors . Thus , preoperative administration of oral PUFA-enriched diets could have an impact on the postoperative inflammatory response after major abdominal surgery", "Objectives : The aim of this study was to investigate the effect of pylorus resection on postoperative delayed gastric emptying ( DGE ) after partial pancreatoduodenectomy ( PD ) . Background : PD is the st and ard treatment for tumors of the pancreatic head . Preservation of the pylorus has been widely accepted as st and ard procedure . DGE is a common complication causing impaired oral intake , prolonged hospital stay , and postponed further treatment . Recently , pylorus resection has been shown to reduce DGE . Methods : Patients undergoing PD for any indication at the University of Heidelberg were r and omized to either PD with pylorus preservation ( PP ) or PD with pylorus resection and complete stomach preservation ( PR ) . The primary endpoint was DGE within 30 days according to the International Study Group of Pancreatic Surgery definition . Results : Ninety-five patients were r and omized to PP and 93 patients to PR . There were no baseline imbalances between the groups . Overall , 53 of 188 patients ( 28.2 % ) developed a DGE ( grade : A 15.5 % ; B 8.8 % ; C 3.3 % ) . In the PP group 24 of 95 patients ( 25.3 % ) and in the PR group 29 of 93 patients ( 31.2 % ) developed DGE ( odds ratio 1.534 , 95 % confidence interval 0.788 to 2.987 ; P = 0.208 ) . Higher BMI , indigestion , and intraabdominal major complications were significant risk factors for DGE . Conclusions : In this r and omized controlled trial , pylorus resection during PD did not reduce the incidence or severity of DGE . The development of DGE seems to be multifactorial rather than attributable to pyloric dysfunction alone . Pylorus preservation should therefore remain the st and ard of care in PD . Trial Registration : German Clinical Trials Register", "Background Delayed gastric emptying ( DGE ) is of considerable concern in patients undergoing pylorus-preserving pancreaticoduodenectomy ( PPPD ) . Prolonged hospital stay , increased cost , and decreased quality of life add on to interventions needed to treat DGE . This study was conducted to determine if performing duodenojejunostomy via the antecolic rather than the retrocolic route improved incidence of DGE . Methods Patients undergoing PPPD between April 2007 and November 2009 were r and omized for either antecolic or retrocolic reconstruction of the duodenojejunostomy . DGE was then assessed by clinical criteria on postoperative day ( POD ) 10 . A paracetamol absorption test was also administered with a liquid meal , and serial plasma levels of intestinal peptides were measured . Results Overall , 64 patients were amenable for analysis : 36 in the antecolic group and 28 in the retrocolic group . The incidences of DGE on POD 10 were 17.6 and 23.1 % ( antecolic vs. retrocolic , respectively ) ( p = 0.628 ) . The two groups did not differ in regard to their median ( interquartile range ) postoperative hospital length of stay [ 13.0 ( 10.0–17.5 ) vs. 12.5 ( 11.0–17.0 ) days ; p = 0.446 ] , time to regular diet [ 5 ( 5–7 ) vs. 5 ( 4–6 ) days ; p = 0.353 ] , or morbidity ( 52.9 vs. 50.0 % ; p = 0.777 ) . The median length of nasogastric tube decompression was similar in the two groups [ 4 ( 3–7 ) vs. 3 ( 3–5 ) days ; p = 0.600 ] . Levels of paracetamol and glucagon-like peptide-1 were markedly decreased in patients with DGE . Conclusions Antecolic reconstruction after PPPD does not improve the occurrence/the incidence of DGE and is similar to retrocolic reconstruction with regard to secondary outcome parameters", "Objectives Nutritional deficiencies and immune dysfunction in cancer patients may contribute to postoperative septic morbidity . This trial compared the effects of perioperative enteral immunonutrition ( EIN ) versus st and ard enteral nutrition ( SEN ) on systemic and mucosal immunity in patients undergoing pancreaticoduodenectomy for periampullary cancer . Methods Thirty-seven patients were r and omized ( EIN , n = 17 ; SEN , n = 20 ) to receive feed for 14 days preoperatively and 7 days postoperatively . Mediators of systemic immunity ( interleukin 1&agr ; , tumor necrosis factor & agr ; , lymphocytes subsets , and complement components ) and of mucosal immunity in duodenal biopsies , nutritional markers and parameters were evaluated . Results The groups were comparable for demographics , the concentrations of mediators of systemic and mucosal immunity at time of recruitment , and for the duration and amount of feed received . Preoperative EIN rather than SEN was associated with significant reductions in plasma tumor necrosis factor & agr ; and total hemolytic complement . Enteral immunonutrition – fed patients had significantly higher total lymphocyte count on the third postoperative day and significantly greater rise in CD4/CD8 ratio from day 3 to day 7 postoperatively compared with SEN-fed patients . Conclusions The perioperative administration of EIN rather than SEN is associated with a favorable modulation of the inflammatory response and enhancement of systemic immunity in patients undergoing pancreaticoduodenectomy for periampullary cancer", "Background Data from observational studies suggest that minimally invasive pancreatoduodenectomy ( MIPD ) is superior to open pancreatoduodenectomy regarding intraoperative blood loss , postoperative morbidity , and length of hospital stay , without increasing total costs . However , several case-matched studies failed to demonstrate superiority of MIPD , and large registry studies from the USA even suggested increased mortality for MIPDs performed in low-volume ( functional recovery is shorter after MIPD compared with open pancreatoduodenectomy , even in an enhanced recovery setting . Methods / design LEOPARD-2 is a r and omized controlled , parallel-group , patient-blinded , multicenter , phase 2/3 , superiority trial in centers that completed the Dutch Pancreatic Cancer Group LAELAPS-2 training program for laparoscopic pancreatoduodenectomy or LAELAPS-3 training program for robot-assisted pancreatoduodenectomy and have performed ≥ 20 MIPDs . A total of 136 patients with symptomatic benign , premalignant , or malignant disease will be r and omly assigned to undergo minimally invasive or open pancreatoduodenectomy in an enhanced recovery setting . After the first 40 patients ( phase 2 ) , the data safety monitoring board will assess safety outcomes ( not blinded for treatment allocation ) and decide on continuation to phase 3 . Patients from phase 2 will then be included in phase 3 . The primary outcome measure is time ( days ) to functional recovery . All patients will be blinded for the surgical approach , at least until postoperative day 5 , but preferably until functional recovery has been attained . Secondary outcome measures are operative and postoperative outcomes , including clinical ly relevant complications , mortality , quality of life , and costs . Discussion The LEOPARD-2 trial is design ed to assess whether MIPD reduces time to functional recovery , as compared with open pancreatoduodenectomy in an enhanced recovery setting .Trial registration Netherl and s Trial Register , NTR5689 . Registered on 2 March 2016", "BACKGROUND The efficacy and feeding-related complications of a nasojejunal feeding tube and jejunostomy after pancreaticoduodenectomy ( PD ) was investigated with a r and omized , controlled clinical trial at the Affiliated Drum Tower Hospital . METHODS Sixty-eight patients who underwent PD in the Department of Hepatobiliary Surgery were r and omly divided into 2 groups : 34 patients received enteral feeding via a nasojejunal tube ( NJT group ) and 34 patients received enteral feeding via a jejunostomy tube ( JT group ) . The assessment of clinical outcome was based on postoperative investigation of complications . The second part of the assessment included tube related complications and an index on catheter efficiency . RESULTS There were 15 cases with infectious complications in the JT group and 13 cases in the NJT group , and there was no significant difference in the rate of infectious complications between the 2 groups . The rate of intestinal obstruction and delayed gastric emptying was significantly decreased in the NJT group ( P Catheter-related complications were more common in the JT group as compared with the NJT group ( 35.3 % vs 20.6 % , P time for removal of the feeding tube and nasogastric tube was significantly decreased in the NJT group . The postoperative hospital stay in the NJT group was significantly decreased ( P hospital mortality in this study . CONCLUSION Nasojejunal feeding is safer than jejunostomy , and it is associated with only minor complications . Nasojejunal feeding can significantly decrease the incidence of delayed gastric emptying and shorten the postoperative hospital stay", "Objective : The aim of this study was to assess the impact of personalized prehabilitation on postoperative complications in high-risk patients undergoing elective major abdominal surgery . Summary Background Data : Prehabilitation , including endurance exercise training and promotion of physical activity , in patients undergoing major abdominal surgery has been postulated as an effective preventive intervention to reduce postoperative complications . However , the existing studies provide controversial results and show a clear bias toward low-risk patients . Methods : This was a r and omized blinded controlled trial . Eligible c and i date s accepting to participate were blindly r and omized ( 1:1 ratio ) to control ( st and ard care ) or intervention ( st and ard care + prehabilitation ) groups . Inclusion criteria were : i ) age > 70 years ; and /or , ii ) American Society of Anesthesiologists score III/IV . Prehabilitation covered 3 actions : i ) motivational interview ; ii ) high-intensity endurance training ; and promotion of physical activity . The main study outcome was the proportion of patients suffering postoperative complications . Secondary outcomes included the endurance time ( ET ) during cycle-ergometer exercise . Results : We r and omized 71 patients to the control arm and 73 to intervention . After excluding 19 patients because of changes in the surgical plan , 63 controls and 62 intervention patients were included in the intention-to-treat analysis . The intervention group enhanced aerobic capacity [ & Dgr;ET 135 ( 218 ) % ; P the number of patients with postoperative complications by 51 % ( relative risk 0.5 ; 95 % confidence interval , 0.3–0.8 ; P = 0.001 ) and the rate of complications [ 1.4 ( 1.6 ) and 0.5 ( 1.0 ) ( P = 0.001 ) ] as compared with controls . Conclusion : Prehabilitation enhanced postoperative clinical outcomes in high-risk c and i date s for elective major abdominal surgery , which can be explained by the increased aerobic capacity ", "BACKGROUND & AIMS Evidence of the advantages of enhanced recovery after surgery ( ERAS ) protocol s following pancreaticoduodenectomy ( PD ) is limited . The aim of this study was to examine the efficiency of ERAS protocol s in patients following PD . METHODS Between June 2014 and October 2016 , patients undergoing PD were r and omly assigned to receive ERAS protocol s or st and ard care . The primary endpoint was the postoperative length of stay . Secondary endpoints included postoperative complications , postoperative quality -of-life ( QoR-40J ) , readmission , and medical cost . RESULTS Of 80 eligible patients , 74 were analyzed in intention-to-treat principles : 37 in the control group and 37 in the ERAS group . The mean length of stay in the ERAS group was significantly shorter than that in the control group ( 20.1 ± 5.4 vs 26.9 ± 13.5 days , P lower percentage of postoperative complications ( 32.4 % vs 56.8 % , P = 0.034 ) and readmissions ( 0 % vs 8.1 % , P = 0.038 ) . Quality -of-life was also significantly better in the ERAS group ( 184 ± 12.4 vs 177 ± 14.5 , P = 0.022 ) . The total medical cost was lower in the ERAS group , but not significantly ( $ 25,445 ± 5065 vs $ 28,384 ± 9999 , P = 0.085 ) . CONCLUSIONS The optimization of ERAS protocol s in patients undergoing PD is safe and accelerates perioperative recovery and quality -of-life , thereby reducing the length of stay . Morbidity was significantly decreased in the ERAS group without compromising surgical outcome . REGISTRATION NUMBER UMIN000014068", "BACKGROUND Early mobilization is considered an important element of postoperative care ; however , how best to implement this intervention in clinical practice is unknown . This systematic review summarizes the evidence regarding the impact of specific early mobilization protocol s on postoperative outcomes after abdominal and thoracic surgery . METHOD The review was performed according to PRISMA guidelines . We search ed 8 electronic data bases to identify studies comparing patients receiving a specific protocol of early mobilization to a control group . Method ologic quality was assessed using the Downs and Black tool . RESULTS Four studies in abdominal surgery ( 3 r and omized controlled trials [ RCTs ] and 1 observational prospect i ve study ) and 4 studies in thoracic surgery ( 3 RCTs and 1 observational retrospective study ) were identified . None of the 5 studies evaluating postoperative complications reported differences between groups . One of 4 studies evaluating duration of stay reported a significant decrease in the intervention group . One of 3 studies evaluating gastrointestinal function reported differences in favor of the intervention group . One of 4 studies evaluating performance-based outcomes reported differences in favor of the intervention group . One of 5 studies evaluating patient-reported outcomes reported differences in favor of the intervention group . Overall method ologic quality was poor . CONCLUSION Few comparative studies have evaluated the impact of early mobilization protocol s on outcomes after abdominal and thoracic surgery . The quality of these studies was poor and results were conflicting . Although bed rest is harmful , there is little available evidence to guide clinicians in effective early mobilization protocol s that increase mobilization and improve outcomes", "OBJECTIVE To evaluate a closed-loop system providing continuous monitoring and strict control of perioperative blood glucose following pancreatic resection . DESIGN Prospect i ve , r and omized clinical trial . PATIENTS Thirty patients who had pancreatic resection for pancreatic neoplasm . INTERVENTIONS Patients were prospect ively r and omized . Perioperative blood glucose levels were continuously monitored using an artificial endocrine pancreas ( STG-22 ) . Glucose levels were controlled using either the sliding scale method ( sliding scale group , n = 13 ) or the artificial pancreas ( artificial pancreas group , n = 17 ) . MAIN OUTCOME MEASURES Incidence of severe hypoglycemia ( patients monitored with the artificial pancreas . The secondary outcome measure was the total amount of insulin required for glycemic control in the first 18 hours after pancreatic resection in each patient group . RESULTS In the sliding scale group , postoperative blood glucose levels rose initially before reaching a plateau of approximately 200 mg/dL between 4 and 6 hours after pancreatectomy . The levels remained high for 18 hours postoperatively . In the artificial pancreas group , blood glucose levels reduced steadily , reaching the target zone ( 80 - 110 mg/dL ) by 6 hours after surgery . The total insulin dose administered per patient during the first postoperative 18 hours was significantly higher in the artificial pancreas group ( mean [ SD ] , 107 [ 109 ] IU ) than the sliding scale group ( 8 [ 6 ] IU ; P hypoglycemia . CONCLUSIONS Perioperative use of an artificial endocrine pancreas to control pancreatogenic diabetes after pancreatic resection is an easy and effective way to maintain near-normal blood glucose levels . The artificial pancreas shows promise for use as insulin treatment for patients with pancreatogenic diabetes after pancreatic resection", "Abstract Background Fluid administration practice s may affect complication rates in some abdominal surgeries , but effects in patients undergoing pancreatectomy are not understood well . We sought to determine whether amount of intraoperative fluid administered to patients undergoing pancreatectomy is associated with postoperative complication rates and to determine whether hospitals vary in their fluid administration practice s. Methods Data for 504 patients undergoing pancreatectomy at 38 hospitals between 2012 and 2015 were evaluated . The main exposure was intraoperative fluid administration ( ≤10 , 10–15 , > 15 mL/kg/h ) . Mortality , complications , and length of stay were the main outcomes of interest . Patient-level associations between exposure and outcome were tested , with adjustment for potentially confounding patient and surgical factors , using r and om intercept , mixed-effects linear or logistic regression models . Hospitals were then categorized as having a restrictive , intermediate , or liberal resuscitation practice , and adjusted outcomes were compared . Results A total of 167 ( 33.1 % ) , 185 ( 36.7 % ) and 152 ( 30.2 % ) patients received restrictive , intermediate , or liberal fluid administration , respectively . Hospitals with more restrictive practice s had significantly lower adjusted 30-day mortality than those with more liberal practice s ( 2.7 vs. 6.6 % ; P lowest rates of severe ( Grade 2 and 3 ) complications ( 15.4 % restrictive vs. 25.3 % intermediate vs. 44.3 % liberal ; P had decreased adjusted mean length of stay ( 9.5 days vs. 12.7 days intermediate vs. 11.6 days liberal ; P More restrictive intraoperative resuscitation practice s in pancreatectomy are associated with decreased hospital-level mortality , severe complications , and length of stay ", "OBJECTIVE To assess the relationship between body temperature and cardiac morbidity during the perioperative period . DESIGN R and omized controlled trial comparing routine thermal care ( hypothermic group ) to additional supplemental warming care ( normothermic group ) . SETTING Operating rooms and surgical intensive care unit at an academic medical center . SUBJECTS Three hundred patients undergoing abdominal , thoracic , or vascular surgical procedures who either had documented coronary artery disease or were at high risk for coronary disease . OUTCOME MEASURE The relative risk of a morbid cardiac event ( unstable angina/ischemia , cardiac arrest , or myocardial infa rct ion ) according to thermal treatment . Cardiac outcomes were assessed in a double-blind fashion . RESULTS Mean core temperature after surgery was lower in the hypothermic group ( 35.4+/-0.1 degrees C ) than in the normothermic group ( 36.7+/-0.1 degrees C ) ( P Perioperative morbid cardiac events occurred less frequently in the normothermic group than in the hypothermic group ( 1.4 % vs 6.3 % ; P=.02 ) . Hypothermia was an independent predictor of morbid cardiac events by multivariate analysis ( relative risk , 2.2 ; 95 % confidence interval , 1.1 - 4.7 ; P=.04 ) , indicating a 55 % reduction in risk when normothermia was maintained . Postoperative ventricular tachycardia also occurred less frequently in the normothermic group than in the hypothermic group ( 2.4 % vs 7.9 % ; P=.04 ) . CONCLUSION In patients with cardiac risk factors who are undergoing noncardiac surgery , the perioperative maintenance of normothermia is associated with a reduced incidence of morbid cardiac events and ventricular tachycardia", "Background : Pancreaticoduodenectomy ( PD ) can be associated with significant blood loss and transfusion requirements , with potential adverse short- and long-term consequences . The aim of this study was to determine whether acute normovolemic hemodilution ( ANH ) , an established blood conservation technique , reduces perioperative allogeneic transfusions in patients undergoing PD . Methods : One hundred thirty patients undergoing PD were r and omized to ANH or st and ard management ( STDM ) . In the ANH group , intraoperative blood collection was performed to a target hemoglobin of 8.0 g/dL ; crystalloid and colloid were used for volume replacement . Strict transfusion triggers were applied during and after operation . Perioperative complications were prospect ively assessed and grade d for severity . Results : From July 2005 to May 2009 , 209 patients were registered , 79 excluded , 65 were r and omized to ANH , and 65 to STD . The groups were well matched for demographic , operative , and histopathologic variables . Patients undergoing ANH received over 2 L more fluid intraoperatively ( 6250 mL , range 2000–11850 ) compared with patients undergoing STD ( 3900 mL , range 2000–9000 ) ( P Transfusion rates were similar ( ANH = 16.9 % , 30 units vs STD = 18.5 % , 33 units ; P = 0.82 ) , as was overall perioperative morbidity ( ANH = 49.2 % vs STD = 47 % , P = 0.86 ) . There was , however , a trend toward more grade -3 complications in patients undergoing ANH ( 32 % vs 23.1 % STD , P = 0.17 ) , and complications related to the pancreatic anastomosis ( leak/fistula/abscess ) were significantly higher in the ANH group ( 21.5 % vs 7.7 % , P = 0.045 ) . The intraoperative fluid volume was higher for all patients with pancreatic anastomotic complications ( n = 19 ) , regardless of r and omization arm ( ANH 6000 mL , range 2800–11350 mL vs STD 5000 mL , range 2000–11850 mL , P patients undergoing PD , ANH did not reduce allogeneic transfusions and result ed in more pancreatic anastomotic complications , likely related to greater intraoperative fluid administration . The benefits of ANH do not necessarily extend to all procedures , and restrictive intravenous fluid management during PD may help improve postoperative outcome", "Summary of Background Data : The role of surgically placed intra-abdominal drainages after pancreatic resections has not been clearly established . In particular , their effect on morbidity rates and the optimal timing for their removal remains controversial . Methods : A total of 114 eligible patients who underwent st and ard pancreatic resections and at low risk of postoperative pancreatic fistula according to our institutional protocol ( amylase value in drains ≤5000 U/L on postoperative day [ POD ] 1 ) were r and omized on POD 3 to receive either early ( POD 3 ) or st and ard drain removal ( POD 5 or beyond ) . The primary end point of the study was the incidence of pancreatic fistula . Secondary endpoints included abdominal complications , pulmonary complications , in-hospital stay , and perioperative mortality . Cost- analysis between the 2 groups was also made . Results : Early drain removal was associated with a decreased rate of pancreatic fistula ( P = 0.0001 ) , abdominal complications ( P = 0.002 ) , and pulmonary complications ( P = 0.007 ) . Median in-hospital stay was shorter ( P = 0.018 ) , and hospital costs decreased ( P = 0.02 ) . Mortality was nil . A significant association with pancreatic fistula was found for timing of drain removal ( P unintentional weight decrease before surgery ( P = 0.022 ) , type of pancreas texture ( P = 0.015 ) , serum amylase levels on POD 1 ( P = 0.001 ) , and albumin levels on POD 1 ( P = 0.039 ) . Multivariate analysis showed that timing of drain removal ( P = 0.0003 ) and unintentional weight decrease before surgery ( P = 0.02 ) were independent risk factors of pancreatic fistula . Conclusions : In patients at low risk of pancreatic fistula , intra-abdominal drains can be safely removed on POD 3 after st and ard pancreatic resections . A prolonged period of drain insertion is associated with a higher rate of postoperative complications with increased hospital stay and costs . The manuscript is a r and omized trial , registered in the NLM data base as NCT00931554", "PURPOSE : Surgical site infection following colorectal surgery is a frequent and costly problem . Barrier protection at the time of this form of surgery has been used with varying results . The aim of this r and omized study was to examine the efficacy of barrier retractional wound protection in the prevention of surgical site infections in open , elective colorectal surgery . METHODS : One hundred thirty consecutive patients undergoing open elective colorectal resectional surgery were r and omly assigned to have either barrier retractional wound protection or st and ard wound retraction . Patients were then followed up for a minimum of 30 days postoperatively . The primary end point was surgical site infection as defined by the Centers for Disease Control and Prevention . The secondary end point was performance of the wound protector as assessed by operating surgeons . RESULTS : There was a significant reduction in the incidence of incisional surgical site infections when the wound protector was used : 3 of 64 ( 4.7 % ) vs 15 of 66 ( 22.7 % ) ; P = .004 . Most surgical site infections were diagnosed after discharge from the hospital ( 78 % ) , and there was no difference in the rates of reoperation , readmission , or formal wound drainage between the 2 groups . Surgeons found the wound protector to be helpful with retraction during surgery , with 88 % ( 7/8 ) adopting it as part of their st and ard setup . CONCLUSIONS : In this study the use of barrier wound protection in elective open colorectal resectional surgery result ed in a clinical ly significant reduction in incisional surgical site infections . Barrier wound protection of this nature should be considered routine in this type of surgery", "BACKGROUND An immune-enhancing diet has been used to alter eicosanoid synthesis , cytokine production , and immune function in an attempt to limit the undesired immune reactions after injury from surgery . This prospect i ve r and omized study was design ed to investigate the effect of preoperative immunonutrition on operative complications , and the participation of prostagl and in E2 ( PGE2 ) on T-cell differentiation in patients undergoing a severely stressful surgery . METHODS The enrolled patients who were scheduled to undergo pancreatoduodenectomy were r and omized into two groups . Patients in the immunonutrition group ( n = 25 ) received oral supplementation containing arginine , ω-3 fatty acids , and RNA for 5 days before the procedure in addition to a 50 % reduction in the amount of regular food . Patients in the control group ( n = 25 ) received no artificial nutrition and were allowed to consume regular food before surgery . All patients received early postoperative enteral infusion of a st and ard formula intended to provide 25 kcal/kg/day . The primary endpoint was the rate of infectious complications ; the secondary endpoint was immune responses . This study is registered with Clinical Trials.gov ( NCT01256034 ) . RESULTS Infectious complication rate and severity of complications ( Clavien-Dindo classification ) were lesser in the immunonutrition group than in the control group . mRNA expression levels of T-bet were greater in the immunonutrition group than in the control group ( P ) . Serum eicosapentaenoic acid and eicosapentaenoic acid/arachidonic acid ratios were greater in the immunonutrition group than in the control group ( P The levels of plasma PGE2 were lesser in the immunonutrition group than in the control group ( P < .05 ) . CONCLUSION Preoperative immunonutrition modulates PGE2 production and T-cell differentiation and may protect against the aggravation of operative complications in patients undergoing pancreatoduodenectomy", "OBJECTIVE To determine the effects of total parenteral nutrition ( TPN ) and enteral nutrition ( EN ) on biochemical and clinical outcomes in pancreatic cancer patients who underwent pancreaticoduodenectomy . METHODS From the year 2006 to 2008 , 60 patients who underwent pancreaticoduodenectomy in Tianjin Third Central Hospital were enrolled in this study . They were r and omly divided into the EN group and the TPN group . The biochemical and clinical parameters were recorded and analyzed between the two groups . RESULTS There was no significant difference in the nutritional status , liver and kidney function , and blood glucose levels between the TPN and EN groups on the preoperative day , the 1st and 3 rd postoperative days . However , on the 7th postoperative day , there was significant difference between the two groups in 24 h urinary nitrogen , serum levels of , total protein ( TP ) , transferrin ( TF ) , alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , alkaline phosphatase ( ALP ) , and γ-glutamyl transpeptadase ( GGT ) , blood urea nitrogen ( BUN ) and creatinine ( Cr ) . On the 14th postoperative day , there was a significant difference between the two groups in terms of urinary levels of 24 h nitrogen , TP , TF , retinol binding protein , ALT , AST , ALP , GGT , total bilirubin , direct bilirubin , BUN , Cr , and glucose . The incidence of delayed gastric emptying in the EN and TPN groups was 0 % and 20 % , respectively . Moreover , the incidence of pancreatic fistulas and hemorrhages in the EN group were 3.6 % and 3.6 % , versus 26.7 % and 30 % in the TPN group , respectively . CONCLUSIONS EN is better than TPN for pancreatic cancer patients who received pancreaticoduodenectomy", "BACKGROUND The optimal target range for blood glucose in critically ill patients remains unclear . METHODS Within 24 hours after admission to an intensive care unit ( ICU ) , adults who were expected to require treatment in the ICU on 3 or more consecutive days were r and omly assigned to undergo either intensive glucose control , with a target blood glucose range of 81 to 108 mg per deciliter ( 4.5 to 6.0 mmol per liter ) , or conventional glucose control , with a target of 180 mg or less per deciliter ( 10.0 mmol or less per liter ) . We defined the primary end point as death from any cause within 90 days after r and omization . RESULTS Of the 6104 patients who underwent r and omization , 3054 were assigned to undergo intensive control and 3050 to undergo conventional control ; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients , respectively . The two groups had similar characteristics at baseline . A total of 829 patients ( 27.5 % ) in the intensive-control group and 751 ( 24.9 % ) in the conventional-control group died ( odds ratio for intensive control , 1.14 ; 95 % confidence interval , 1.02 to 1.28 ; P=0.02 ) . The treatment effect did not differ significantly between operative ( surgical ) patients and nonoperative ( medical ) patients ( odds ratio for death in the intensive-control group , 1.31 and 1.07 , respectively ; P=0.10 ) . Severe hypoglycemia ( blood glucose level , conventional-control group ( P median number of days in the ICU ( P=0.84 ) or hospital ( P=0.86 ) or the median number of days of mechanical ventilation ( P=0.56 ) or renal-replacement therapy ( P=0.39 ) . CONCLUSIONS In this large , international , r and omized trial , we found that intensive glucose control increased mortality among adults in the ICU : a blood glucose target of 180 mg or less per deciliter result ed in lower mortality than did a target of 81 to 108 mg per deciliter . ( Clinical Trials.gov number , NCT00220987 .", "BACKGROUND Postoperative pancreatic fistula ( postoperative pancreatic fistula [ POPF ] ) is the most common complication after pancreaticoduodenectomy . Despite some studies showing little effect of octreotide in unselected patients , we hypothesized that in high-risk patients depot octreotide may reduce the risk of POPF . METHODS Sixty-eight patients were prospect ively evaluated for inclusion in the current study . Two groups were identified : pancreatic ducts ≤3 mm ( high risk ) and those with ducts > 3 mm ( low risk ) . Thirty-two patients were low risk , whereas 36 patients were high risk . High-risk patients were treated preoperatively with depot octreotide and begun on an intravenous drip for 24 hours . Low-risk patients underwent pancreaticoduodenectomy without pharmacologic intervention . In contrast , the control cohort represents 106 retrospectively analyzed patients who underwent a pancreaticoduodenectomy without depot octreotide injection without regard to low- or high-risk status . RESULTS Overall , POPF was 11 of 68 ( 16 % ) . Nine of 36 high risk patients treated with depot octreotide developed POPF ( 25 % ) , and 2 of 32 low risk patients developed POPF ( 6 % ) . In the control cohort of high-risk patients , 9 of 44 ( 20 % ) and 3 of 62 ( 5 % ) low-risk patients developed POPF ( P = .628 when comparing the development of POPF in high-risk patients with or without pharmacologic intervention ) . CONCLUSIONS Prophylactic use of depot octreotide in high-risk patients does not result in reduced incidence of POPF . Duct size has a significant impact on the occurrence of POPF", "BACKGROUND & AIMS Protocol s for enhanced recovery provide comprehensive and evidence -based guidelines for best perioperative care . Protocol implementation may reduce complication rates and enhance functional recovery and , as a result of this , also reduce length-of-stay in hospital . There is no comprehensive framework available for pancreaticoduodenectomy . METHODS An international working group constructed within the Enhanced Recovery After Surgery ( ERAS ® ) Society constructed a comprehensive and evidence -based framework for best perioperative care for pancreaticoduodenectomy patients . Data were retrieved from st and ard data bases and personal archives . Evidence and recommendations were classified according to the GRADE system and reached through consensus in the group . The quality of evidence was rated \" high \" , \" moderate \" , \" low \" or \" very low \" . Recommendations were grade d as \" strong \" or \" weak \" . RESULTS Comprehensive guidelines are presented . Available evidence is summarised and recommendations given for 27 care items . The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations . CONCLUSIONS The present evidence -based guidelines provide the necessary platform upon which to base a unified protocol for perioperative care for pancreaticoduodenectomy . A unified protocol allows for comparison between centres and across national borders . It facilitates multi-institutional prospect i ve cohort registries and adequately powered r and omised trials", "BACKGROUND Although mortality following pancreaticoduodenectomy is decreasing , postoperative morbidity remains high . It was hypothesized that culture-directed treatment of bacteriobilia would decrease the incidence of infectious complications following pancreaticoduodenectomy . METHODS In a retrospective study of 197 pancreaticoduodenectomy patients , those in the control group ( n = 128 , 2005 - 2009 ) were given perioperative prophylactic antibiotics , whereas those in the treatment group ( n = 69 , 2009 - 2011 ) were continued on antibiotics until intraoperative bile culture results became available . Patients with bacteriobilia received 10 days of antibiotic treatment , which was otherwise discontinued in patients without bacteriobilia . Various complication rates were compared using Fisher 's exact test for categorical variables , Wilcoxon rank sum test for ordinal variables , and a two- sample t-test for continuous variables . RESULTS Demographics , comorbidities , baseline clinical characteristics , and intraoperative and postoperative variables were similar between the two groups . There were higher incidences of elevated creatinine ( 19 % versus 4 % ; P = 0.004 ) and preoperative hyperglycaemia ( 18 % versus 7 % ; P = 0.053 ) in the control group . Fewer patients in the control group underwent preoperative biliary stenting ( 48 % versus 67 % ; P = 0.017 ) and intraperitoneal drains were placed at the time of resection more frequently in the control group ( 85 % versus 38 % ; P rate of postoperative wound infections ( 12 % in the control group versus 3 % in the treatment group ; P = 0.036 ) and overall complication severity score ( 1 in the control group versus 0 in the treatment group ; P = 0.027 ) . CONCLUSIONS Prolonged antibiotic therapy for bacteriobilia may decrease postoperative wound infection rates after pancreaticoduodenectomy . A r and omized prospect i ve trial is warranted to provide evidence to further support this practice", "BACKGROUND Octreotide is generally administered based on the surgeon 's interpretation of perceived risk for pancreatic fistula at the time of pancreaticoduodenectomy ( PD ) . METHODS A single-institution , prospect i ve r and omized trial was conducted between April 2009 and December 2011 involving 62 PD patients who were r and omized to receive octreotide ( 100 μg subcutaneously every 8 h ; n = 32 ) or placebo ( n = 30 ) . Pancreatic juice output was measured after the operation using a catheter inserted into the pancreatic duct . Postoperative complications were recorded . RESULTS No significant differences in median output were found between the octreotide ( 82.5 ml ) and placebo ( 77.5 ml ) groups ( P = 0.538 ) . Median total output was significantly lower in patients with adenocarcinoma compared with those with periampullary tumours ( P = 0.004 ) and in patients with a duct diameter of > 5 mm compared with those with a duct diameter of differences in overall morbidity between the octreotide and placebo groups ( P = 0.819 ) . Grade B pancreatic fistula ( International Study Group for Pancreatic Fistula ) was observed in two and three patients in the octreotide and placebo groups , respectively . CONCLUSIONS Morbidity did not differ significantly between the groups . This study did not demonstrate an inhibitory effect of octreotide on exocrine pancreatic secretion . Based on these results , the routine use of octreotide after PD can not be recommended", "Objectives : The aim of this study was to compare nasojejunal early enteral nutrition ( NJEEN ) with total parenteral nutrition ( TPN ) , after pancreaticoduodenectomy ( PD ) , in terms of postoperative complications . Background : Current nutritional guidelines recommend the use of enteral over parenteral nutrition in patients undergoing gastrointestinal surgery . However , the NJEEN remains controversial in patients undergoing PD . Methods : Multicenter , r and omized , controlled trial was conducted between 2011 and 2014 . Nine centers in France analyzed 204 patients undergoing PD to NJEEN ( n = 103 ) or TPN ( n = 101 ) . Primary outcome was the rate of postoperative complications according to Clavien-Dindo classification . Successful NJEEN was defined as insertion of a nasojejunal feeding tube , delivering at least 50 % of nutritional needs on PoD 5 , and no TPN for more than consecutive 48 hours . Results : Postoperative complications occurred in 77.5 % [ 95 % confidence interval ( 95 % CI ) 68.1–85.1 ] patients in the NJEEN group versus 64.4 % ( 95 % CI 54.2–73.6 ) in TPN group ( P = 0.040 ) . NJEEN was associated with higher frequency of postoperative pancreatic fistula ( POPF ) ( 48.1 % vs 27.7 % , P = 0.012 ) and higher severity ( grade B/C 29.4 % vs 13.9 % ; P = 0.007 ) . There was no significant difference in the incidence of post-pancreatectomy hemorrhage , delayed gastric emptying , infectious complications , the grade of postoperative complications , and the length of postoperative stay . A successful NJEEN was achieved in 63 % patients . In TPN group , average energy intake was significantly higher ( P patients undergoing PD , NJEEN was associated with an increased overall postoperative complications rate . The frequency and the severity of POPF were also significantly increased after NJEEN . In terms of safety and feasibility , NJEEN should not be recommended", "Introduction Epidural analgesia has emerged as a commonly applied method to improve pain management and reduce perioperative complications in major abdominal surgery . However , there is no detailed analysis of its efficacy for pancreatic operations . This study compares clinical and economic outcomes after epidural and intravenous analgesia for pancreatoduodenectomy . Material and methods Data for 233 consecutive patients , who underwent pancreatoduodenectomy , were prospect ively acquired and retrospectively review ed at a single institution , pancreato-biliary specialty practice . From October 2001 to February 2007 , all patients were offered thoracic epidural analgesia , and those who declined received intravenous analgesia . Perioperative pain management was dictated as an element of a st and ardized clinical pathway for pancreatic resections . Clinical and economic outcomes were analyzed and compared for epidural analgesia and intravenous analgesia groups . Results One hundred eighty-five patients received epidural analgesia , and 48 received intravenous analgesia , with equivalent baseline patient demographics between the groups . Patients administered epidural analgesia had lower pain scores but significantly higher rates of major complications . Pancreatic fistulae and postoperative ileus occurred more frequently , and patients with epidural analgesia more often required discharge to rehabilitation facilities . A trend towards longer hospitalizations was observed among epidural analgesia patients , but total costs were statistically equivalent between the groups . Further analysis demonstrates that 31 % of epidural infusions were aborted before anticipated ( fourth postoperative day ) because of hemodynamic compromise and /or inadequate analgesia . These select patients required more transfusions , aggressive fluid resuscitation , and subsequently suffered even higher rates of gastrointestinal and respiratory complications , all attributing to higher costs . Multivariate analysis demonstrates that preoperative hematocrit concentration less than 36 % , elderly age ( > 75 years ) , and chronic pancreatitis predict failure of epidural infusions . Conclusion Thoracic epidural analgesia after pancreatic resections is associated with hemodynamic instability , which may compromise enteric anastomoses , gastrointestinal recovery , and respiratory function . These outcomes are exacerbated in poorly functioning epidurals and suggest that epidural analgesia may not be the optimal method for perioperative pain control when pancreatoduodenectomy is performed", "Purpose Mosapride citrate ( mosapride ) is a serotonin 5-hydroxytryptamine 4 receptor agonist known to promote gastric emptying and large-intestine motility . We assessed the effect of mosapride on postoperative ileus following colon surgery . Methods Forty patients with colon cancer undergoing h and -assisted laparoscopic colectomy were r and omly assigned to a mosapride group or a control group . The mosapride group received 15 mg of mosapride by mouth with 50 ml of water three times a day , starting on postoperative day 1 . The control group received 50 ml of water on the same schedule . Patients were allowed to resume oral feeding on the evening of postoperative day 2 . Postoperative time to first bowel movement was evaluated by one investigator blinded to treatment . Postoperative gastric emptying was evaluated with the [13C]-acetate breath test at 24 and 48 hours after the operation . Results Postoperative time to first bowel movement was significantly shorter in the mosapride group than in the control group ( 48.5 vs. 69.3 hours , P = 0.0149 ) . The time to maximal gastric emptying rate as determined by the breath test was significantly shorter in the mosapride group than in the control group at the 48-hour time point ( 27.9 vs. 35.3 minutes , P = 0.0294 ) . Postoperative hospital stay was shorter in patients receiving mosapride than in controls ( 6.7 vs. 8.4 days , P = 0.0398 ) . No adverse effects were observed with mosapride . Conclusions Gastric emptying was improved by mosapride . The results suggested that the period of postoperative ileus following h and -assisted laparoscopic colectomy can be shortened by treatment with mosapride", "We prospect ively examined the incidence of postoperative nausea and vomiting ( PONV ) in a group of 193 elderly surgical in patients receiving no postoperative antiemetic prophylaxis . Risk factors for PONV and detailed data on postoperative opioid use were recorded . The overall postoperative vomiting ( POV ) rate was 23.8 % , whereas postoperative nausea ( PON ) was 51.3 % . Opioid use ( P = 0.025 ) , and female gender ( P = 0.038 ) were identified as significantly influencing POV in this relatively small population . There was a strong logarithmic dose-response relationship between postoperative opioid dose and POV ( r2 = 0.98 , P PON ( r2 = 0.98 , P = 0.01 ) . Use of patient-controlled analgesia or epidural analgesia was a marker for large-dose opioid use ( P POV in the 24-h postoperative period of 41 % and 31 % respectively , compared with 11 % for other patients ( P POV should treat postoperative opioid use as a continuous variable , rather than treat it as a dichotomous variable", "We included 34 trials with 3742 participants , identified through 6 data base and supplementary search es ( to May 2017 ) : 29 were r and omised ; 4 were quasi‐r and omised and 1 was cluster‐r and omised . Disparate measurements and outcomes precluded meta‐analyses . Blinding was attempted in only 6 out of 34 ( 18 % ) trials . A multimedia format , alone or in combination with text or verbal formats , was studied in 20/34 ( 59 % ) trials : pre‐operative anxiety was unaffected in 10 out of 14 trials and reduced by the multimedia format in three ; postoperative anxiety was unaffected in four out of five trials in which formats were compared . Multimedia formats increased knowledge more than text , which in turn increased knowledge more than verbal formats . Other outcomes were unaffected by information format . The timing of information did not affect pre‐operative anxiety , postoperative pain or length of stay . In conclusion , the effects of pre‐operative information on peri‐operative anxiety and other outcomes were affected little by format or timing", "Objective : To develop and vali date a simple prognostic score to predict major postoperative complications after pancreaticoduodenectomy ( PD ) . Background : PD still carries a high rate of severe postoperative complications . No specific score is currently available to stratify the patient 's risk of major morbidity . Methods : Between 2002 and 2010 , preoperative , intraoperative , and outcome data from 700 consecutive patients undergoing PD in our institution were prospect ively collected in an electronic data base . Major complications were defined as levels III to V of Clavien-Dindo classification . On the basis of a multivariate regression model , the score was developed using a r and om two-thirds of the population ( n = 469 ) and was vali date d on the remaining 231 patients . Results : Major complication rate was 16.7 % ( 117/700 ) . Significant predictors included in the scoring system were : pancreas texture , pancreatic duct diameter , operative blood loss , and ASA score . The mean risk of developing major postoperative complications was 7 % in patients with score 0 to 3 , 13 % in patients with score 4 to 7 , 23 % in patients with score 8 to 11 , and 36 % in patients with score 12 to 15 . In the validation population , the predicted risk of major complications was 15.2 % versus a 16.9 % observed risk ( C-statistic index = 0.743 ) . Conclusion : This new score may accurately predict a patient 's postoperative outcome . Early identification of high-risk patients could help the surgeon to adopt intraoperative and postoperative strategies tailored on individual basis", "Abstract Background : The aim of the study was to evaluate the influence of low dose perioperative Octreotide on the prevention of complications ( pancreatic fistula and general complications ) in patients undergoing pancreatic surgery followed by pancreatico-jejunostomy . Material and Methods : 105 patients were r and omized to receive either Octreotide 0.1 mg subcutaneously 3 times/day for a total of 7 days or no Octreotide . The primary endpoints were the occurrence of a pancreatic fistula and /or general complications including the length of hospital stay . There were 25 surgical draining procedures performed and 80 duodeno-pancreatectomies with or without preservation of the pylorus . Twenty-six ( 24.8 % ) of the patiënts were treated for chronic pancreatitis , 8 ( 7.6 % ) for benign tumoral disease and 71 ( 67.6 % ) for carcinoma . All patients underwent pancreatico-jejunostomy . Results : 56 patients received Octreotide and 49 did not . The incidence of fistula formation in the Octreotide group was 8.9 % ( n = 5 ) and in the control group 8.2 % ( n = 4 ) for a total incidence of 8.5 % . The difference between the two groups was not statistically significant . There was one death in the Octreotide group and none in the control group for an overall mortality of 0.9 % . The morbidity , except fistulas , was 10.7 % in the Octreotide group and 12.2 % in the control group . The length of hospital stay was 23.1 ± 15.1 days in the group receiving Octreotide vs 20.4 ± 8.1 days in the control group ( p = 0.808 ) . Stratifying the data for duodenopancreatectomy and for draining procedures there was no difference between the groups either . Conclusion : In patients undergoing pancreatic surgery and pancreatico-jejunostomy , the perioperative use of 3 χ 0.1 mg Octreotide for 7 days does not reduce general complications nor fistula formation", "Objective : This dual-center , r and omized , controlled , noninferiority trial aim ed to prove that omission of drains does not increase reintervention rates after pancreatic surgery . Background : There is considerable uncertainty regarding intra-abdominal drainage after pancreatoduodenectomy . Methods : Patients undergoing pancreatic head resection with pancreaticojejunal anastomosis were r and omized to intra-abdominal drainage versus no drainage . Primary endpoint was overall reintervention rate ( relaparotomy or radiologic intervention ) . Secondary endpoints were clinical ly relevant pancreatic fistula ( grade B/C ) , mortality , morbidity , and hospital stay . The planned sample size was 188 patients per group . Results : A total of 438 patients were r and omized . Forty-three patients ( 9.8 % ) were excluded because no pancreatic anastomosis was performed , and 395 patients ( 202 drain , 193 no-drain ) were analyzed . Reintervention rates were not inferior in the no-drain group ( drain 21.3 % , no-drain 16.6 % ; P = 0.0004 ) . Overall in-hospital mortality ( 3.0 % ) was the same in both groups ( drain 3.0 % , no-drain 3.1 % ; P = 0.936 ) . Overall surgical morbidity ( 41.8 % ) was comparable ( P = 0.741 ) . Clinical ly relevant pancreatic fistula ( grade B/C : drain 11.9 % , no-drain 5.7 % ; P = 0.030 ) and fistula-associated complications ( drain 26.4 % ; no drain 13.0 % ; P = 0.0008 ) were significantly reduced in the no-drain group . Operation time ( P = 0.093 ) , postoperative hemorrhage ( P = 0.174 ) , intra-abdominal abscess formation ( P = 0.199 ) , biliary leakage ( P = 0.382 ) , delayed gastric emptying ( P = 0.062 ) , burst abdomen ( P = 0.480 ) , wound infection ( P = 0.758 ) , and hospital stay ( P = 0.487 ) did not show significant differences . Conclusions : Omission of drains was not inferior to intra-abdominal drainage in terms of postoperative reintervention and superior in terms of clinical ly relevant pancreatic fistula rate and fistula-associated complications . There is no need for routine prophylactic drainage after pancreatic resection with pancreaticojejunal anastomosis", "BACKGROUND The factors associated with delayed gastric emptying ( DGE ) after a pancreaticoduodenectomy ( PD ) are not definitively known . METHODS From November 2011 through to May 2012 , data were prospect ively collected on 711 patients undergoing a pancreaticoduodenectomy or total pancreatectomy as part of the American College of Surgeons-National Surgical Quality Improvement Program Pancreatectomy Demonstration Project . Bivariate and multivariate models were employed to determine the factors that predicted DGE . RESULTS In the 711 patients , the overall rate of DGE was 20.1 % . In a bivariate analysis , intra-operative factors such as pylorus-preservation ( 47.1 % versus 43.7 % , P = 0.40 ) , intra-operative drain placement ( 85.5 % , versus 85.1 % , P = 0.91 ) and an antecolic compared with a retrocolic gastrojejunostomy ( 60.1 % versus 65.1 % , P = 0.26 ) were not different between the DGE and no DGE groups . Pancreatic fistula formation ( 31.2 % versus 10.1 % ) , post-operative sepsis ( 21.7 % versus 7.0 % ) , organ space surgical site infection ( SSI ) ( 23.9 % versus 7.9 % ) , need for percutaneous drainage ( 23.0 % versus 10.6 % ) and reoperation ( 10.6 % versus 3.1 % ) were higher in patients with DGE ( P pancreatic fistula , post-operative sepsis and reoperation were independently associated with DGE . DISCUSSION In this multicentre study , only post-operative complications were associated with DGE . Neither pylorus preservation nor route of enteric reconstruction ( antecolic versus retrocolic ) was associated with delayed gastric emptying", "A prospect i ve , r and omized , controlled trial was performed to determine the efficacy of somatostatin in the prevention of pancreatic stump-related complications with elimination of surgeon-related factors in high-risk patients undergoing panceaticoduodenectomy . From August 1997 to December 2000 , 54 patients , 28 men and 26 women , with age ranged from 32 to 89 years , were r and omly assigned to somatostatin group ( n = 27 ) or placebo group ( n = 27 ) . Ninety-four percent of the patients had pancreatic and periampullary lesions ; 6 % had secondary lesion involving the duodenum such as local recurrent colon carcinoma and renal cell carcinoma . These patients received either st and ard pancreaticoduodenectomy or pylorus-preserving pancreaticoduodenectomy . An experienced surgeon performed all operations in same fashion to minimize the surgical factor . A transanastomotic tube was inserted into the pancreatic duct for diversion of pancreatic juice in the pancreaticojejunostomy for a 3-weeks period postoperatively . Intravenous infusion of somatostatin was given at a dose of 250μg/hr in the somastotatin group and normal saline was given to the control group for 7 days postoperatively . There was one perioperative death in each group , result ing in a 3.7 % mortality rate . In the somastotatin group , as compared to the placebo group , the incidence of overall morbidity and pancreatic stump related complications were significantly lower with a mean decrease of 50 % pancreatic juice output and a slightly shorter duration of hospital stays . In conclusion , after excluding surgeon related factor , prophylactic use of somatostatin reduces the incidence and severity of pancreatic stump related complications in high-risk patients having pancreaticoduodenectomy via decreased secretion of pancreatic exocrine", "Somatostatin inhibits gastroenteropancreatic exocrine secretion and is often used after pancreaticoduodenectomy to reduce pancreatic secretion to minimize tissue damage and pancreatic stump complications . Because our earlier clinical work saw a major increase in delayed gastric emptying ( DGE ) with somatostatin prophylaxis after pylorus-preserving pancreaticoduodenectomy ( PPPD ) , this small-group study was design ed to confirm or disprove that observation . From August 1997 to December 2000 , a total of 23 post-PPPD patients were r and omized to receive somatostatin prophylaxis [ somatostain ( + ) ] ( n = 11 ) or not [ somatostatin ] ( − ) ( n = 12 ) . The incidence of DGE , scintographic solid-phase emptying results on day 14 postoperatively , and sequential fasting plasma motilin levels were compared , as motilin levels are related to both gastric motility and somatostatin levels . The somatostatin(+ ) group exhibited greatly increased patient complaints of DGE : 9 of 11 ( 82 % ) versus 3 of 12 ( 25 % ) in the somatostatin(− ) group . Radiologic scintography showed somatostatin prophylaxis prolonged the half-time ( T1/2 ) of solid-phase emptying : 144.5 ± 51.4 minutes for somatostatin(+ ) versus 89.0 ± 59.9 minutes for somatostatin(− ) ( p plasma motilin levels prior to somatostatin infusion , motilin decreased 80 % in reaction to the surgery . For somatostatin(− ) patients , motilin levels oscillated , or “ rang , ” postoperatively , reaching a higher level on day 3 , declined to a new record minimum on day 7 , and by day 21 were 50 % of the original and the slope of the recovery curve was increasing well . In somatostatin(+ ) patients the same ringing pattern was observed but decreased with motilin levels 30 % to 70 % lower than in the somatostatin(− ) patients . By day 21 somatostatin(+ ) motilin levels were recovering but still only 20 % original levels , and the slope of the recovery curve was not optimistic . On postoperative day 14 the plasma motilin levels ( below approximately 6 bg/ml ) correlated strongly with DGE for both groups . Despite the small sample size , the results indicated that ( 1 ) somatostatin prophylaxis significantly decreases fasting plasma motilin ; ( 2 ) somatostatin prophylaxis produces lingering suppression of plasma motilin ; ( 3 ) PPPD surgery itself significantly reduces fasting motilin levels with recovery to 50 % normal at day 21 ; ( 4 ) the mechanism of somatostatin-induced DGE seems related to reduced fasting plasma motilin levels", "Background A recent r and omized , controlled trial investigating intraperitoneal drain use during pancreatoduodenectomy ( PD ) had a primary goal of assessing overall morbidity . It was terminated early with findings that routine elimination of drains in PD increases mortality and the severity and frequency of overall complications . Here , we provide a follow-up analysis of drain value in reference to clinical ly relevant postoperative pancreatic fistula ( CR-POPF ) . Methods Nine institutions performed 137 PDs , with patients r and omized to intraperitoneal drainage ( N = 68 ) or no drainage ( N = 69 ) . The Fistula Risk Score ( FRS ) , a 10-point scale derived from four vali date d risk factors for CR-POPF , facilitated risk adjustment between treatment groups . Results There was no difference in fistula risk between the two cohorts . Overall , CR-POPF rates were higher in the no drain group compared to the drain group ( 20.3 vs. 13.2 % ; p = 0.269 ) . Patients with negligible/low FRS risk had higher rates of CR-POPF when drains were used ( 14.8 vs. 4.0 % ; p = 0.352 ) . Conversely , there were significantly fewer CR-POPFs ( 12.2 vs. 29.5 % ; p = 0.050 ) when drains were used with moderate/high risk patients . Lastly , moderate/high risk patients who suffered a CR-POPF had reduced 90-day mortality ( 22.2 vs. 42.9 % ) when a drain was used . Conclusion The results of this analysis suggest that drains diminish the rate and severity of CR-POPF in patients with moderate/high risk , but they could possibly be avoided in the roughly one third of patients with negligible/low risk", "Objective : The aim of this trial was to investigate whether a routine of allowing normal food at will increases morbidity after major upper gastrointestinal ( GI ) surgery . Summary Background Data : Nil-by-mouth with enteral tube feeding is widely practice d for several days after major upper GI surgery . After other abdominal operations , normal food at will has been shown to be safe and to improve gut function . Methods : Patients were r and omly assigned to a routine of nil-by-mouth and enteral tube feeding by needle-catheter jejunostomy ( ETF group ) or normal food at will from the first day after major upper GI surgery . Primary end point was rate of major complications and death . Secondary outcomes were minor complications and adverse events , bowel function , and length of stay . All patients were invited to a follow-up at 8 weeks after discharge from the hospital . Results : Four hundred fifty-three patients who underwent major open upper GI surgery in 5 centers were enrolled between 2001 and 2006 . Four hundred forty-seven patients were correctly r and omized . Of 227 patients 76 ( 33.5 % ) had major complications in the ETF group compared with 62 ( 28.2 % ) of 220 patients allowed normal food at will ( P = 0.26 , 95 % CI for the difference in rate from −3.3 to 13.9 ) . In the ETF group , 36 ( 15.9 % ) patients were reoperated compared with 29 ( 13.2 % ) in the group allowed normal food at will ( P = 0.50 ) and 30-day mortality was 10 ( 4.4 % ) of 227 and 11 ( 5.0 % ) of 220 patients , respectively ( P = 0.83 ) . Time to resumed bowel function was significantly in favor of allowing normal food at will ( P = 0.01 ) , as were the total number of major complications , length of stay , and rate of postdischarge complications . Conclusions : Allowing patients to eat normal food at will from the first day after major upper GI surgery does not increase morbidity compared with traditional care with nil-by-mouth and enteral feeding", "OBJECTIVES Aim of this study is the evaluation of the impact of a multimedia CD ( MCD ) on preoperative anxiety and postoperative recovery of patients undergoing elective laparoscopic cholecystectomy ( LC ) . METHODS Sixty consecutive c and i date s for elective LC were r and omly assigned to four groups . Group A included 15 patients preoperatively informed regarding LC through the MCD presented by Registered Nurse ( RN ) . Patients in group B ( n = 15 ) were informed through a leaflet . Patients in group C ( n = 15 ) were informed verbally from a RN . Finally , the control Group D included 15 patients informed conventionally by the attending surgeon and anesthesiologist , as every other patient included in groups A , B , and C. Preoperative assessment of knowledge about LC was performed after each informative session through a question naire . Evaluation of preoperative anxiety was conducted using APAIS scale . Postoperative pain and nausea scores were measured using an NRS scale , 16 hours after the patient had returned to the ward . RESULTS Statistical processing of the results ( single linear regression ) showed that patients in groups A , B , and C achieved a higher knowledge score , less preoperative anxiety score and less postoperative pain and nausea , compared to Group D. In multiple regression analysis , group A had a higher knowledge score compared to the four groups ( p knowledge , especially in day-surgery cases , like LC", "INTRODUCTION The Joint Commission Surgical Care Improvement Project ( SCIP ) includes performance measures aim ed at reducing surgical site infections ( SSI ) . One measure defines approved perioperative antibiotics for general operative procedures . However , there may be a subset of procedures not adequately covered with the use of approved antibiotics . We hypothesized that piperacillin-tazobactam is a more appropriate perioperative antibiotic for pancreaticoduodenectomy ( PD ) . METHODS In collaboration with hospital epidemiology and the Division of Infectious Diseases , we retrospectively review ed records of 34 patients undergoing PD between March and May 2008 who received SCIP-approved perioperative antibiotics and calculated the SSI rate . After changing our perioperative antibiotic to piperacillin-tazobactam , we prospect ively review ed PDs performed between June 2008 and March 2009 and compared the SSI rates before and after the change . RESULTS For 34 patients from March through May 2008 , the SSI rate for PD was 32.4 per 100 cases . Common organisms from wound cultures were Enterobacter and Enterococcus ( 50.0 % and 41.7 % , respectively ) , and these were cefoxitin resistant . From June 2008 through March 2009 , 106 PDs were performed . During this period , the SSI rate was 6.6 per 100 surgeries , 80 % lower than during March through May 2008 ( relative risk , 0.204 ; 95 % confidence interval [ CI ] , 0.086 - 0.485 ; P = .0004 ) . CONCLUSION Use of piperacillin-tazobactam as a perioperative antibiotic in PD may reduce SSI compared with the use of SCIP-approved antibiotics . Continued evaluation of SCIP performance measures in relationship to patient outcomes is integral to sustained quality improvement", "STUDY OBJECTIVE To determine the effect of two target dexmedetomidine infusions ( 0.3 ng/ml and 0.6 ng/ml ) on the minimal alveolar concentration ( MAC ) of sevoflurane in adults age 55 to 70 years . DESIGN Prospect i ve , r and omized , placebo-controlled study . SETTING University-affiliated hospital . PATIENTS 45 ASA physical status I and II adults , age 55 to 70 years , undergoing elective surgery with at least a 3 inch skin incision . INTERVENTIONS Patients were given a dexmedetomidine or placebo infusion for at least 15 minutes before anesthetic induction with sevoflurane in oxygen by face mask . After tracheal intubation , a target sevoflurane concentration was maintained for 15 minutes while the dexmedetomidine or placebo infusion continued to run . MEASUREMENTS AND MAIN RESULTS At the time of skin incision , two observers independently determined movement or nonmovement to the incision . Blood sample s for dexmedetomidine were taken before the infusion and at the time of skin incision . The dexmedetomidine plasma concentrations were 0 before infusion with all treatment groups . At the time of incision , they were 0 in the placebo group , 0.39 + /- 0.13 ng/ml in the 0.3 ng/ml target group , and 0.7 + /- 0.13 ng/ml in the 0.6 ng/ml target group . The MAC of sevoflurane was 1.83 % in the placebo group , 1.78 % in the 0.3 ng/ml target dexmedetomidine group , and 1.51 % in the 0.6 ng/ml target dexmedetomidine group . CONCLUSIONS Dexmedetomidine 0.7 ng/ml decreased the MAC of sevoflurane by 17 % , whereas there was no difference between the placebo and the dexmedetomidine 0.39 ng/ml group", "Making a diagnosis is the bread and butter of clinical practice , but in light of the number of tests now available to clinician , diagnosing illness has become a complicated process . Guidelines for making an evidence -based diagnosis abound , but those making recommendations about diagnostic tests or test strategies must realize that clinicians require support to make diagnostic decisions that they can easily implement in daily practice . The Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) Working Group has developed a rigorous , transparent , and increasingly adopted approach for grading the quality of research evidence and strength of recommendations to guide clinical practice . This editorial summarizes GRADE 's process for developing recommendations for tests ( 1 ) . Clinicians are trained to use tests for screening and diagnosis ; identifying physiologic derangements ; establishing a prognosis ; and monitoring illness and treatment response by assessing signs and symptoms , imaging , biochemistry , pathology , and psychological testing techniques ( 2 ) . Sensitivity , specificity , positive predictive value , likelihood ratios , and diagnostic odds ratios are among the challenging terms that diagnostic studies typically deliver to clinicians , and all have to do with diagnostic accuracy . Not only do clinicians have difficulties remembering the definitions and calculations for these terms , application of the concepts to individual patients is often complicated . Many clinicians order a test despite uncertainty about how to interpret the result , and they also contribute to testing errors by incorrectly ordering tests ( 3 , 4 ) . GRADE 's framework for developing recommendations for diagnostic management studies is based on what is needed for practical clinical applicationthat is , how to weigh the benefits and harms of ordering and using a diagnostic test in caring for patients ( 1 ) . The approach begins with specifying the PICO : the relevant population ( P ) , diagnostic intervention or test ( I ) ( including its purpose , such as triage , replacement , or an add-on test ) , comparison test ( C ) , and patient-important outcomes ( O ) related to the use of a test for a focused clinical question . If a test fails to improve patient-important outcomes , there is no reason to use it , whatever its accuracy . For example , the results of genetic testing for Huntington chorea , an untreatable condition , may provide either welcome reassurance that a patient will not have the condition or the ability to plan for his future knowing that he will sadly fall victim ( 1 ) . Here , the ability to plan is analogous to an effective treatment , and the benefits of planning need to be balanced against the downsides of receiving an early diagnosis ( 5 - 7 ) . The best evidence of test performance comes from large r and omized trials of diagnostic strategies that directly measure patient-important outcomes ( 1 ) . However , these trials are few and far between : An informal review of the Cochrane data base of r and omized trials revealed . In the first step , a diagnostic-test accuracy study ( Figure ) , patients may receive both a new test and a reference test ( i.e. , the best available method for detecting the target condition ) . Investigators can then calculate the accuracy of the test compared with the reference test ( first step ) . In the second step , judgments about the patient importance of test accuracy are based on the consequences of being correctly or incorrectly classified as having or not having the disease . These include the benefits and harms of receiving treatment or follow-up tests for those correctly classified as having the disease , reassurance or receipt of other follow-up tests for those correctly classified as not having the disease , receipt of unnecessary treatment or additional tests for those incorrectly classified as having the disease , delayed or no treatment for those incorrectly classified as not having the disease , and any adverse effects of the diagnostic test ( e.g. , from invasive tests ) . Those making recommendations about diagnostic tests must then compare patient-important outcomes ( and costs ) in all patients receiving the new test with all patients receiving the old , or comparator , test . For the first step ( i.e. , assessing test accuracy ) , there are well-described method ological criteria for assessing risk for bias in an estimate of test accuracy , ideally based on a systematic review of relevant studies . For instance , studies of diagnostic test accuracy with a low risk for bias enroll consecutive patients for whom there is legitimate diagnostic uncertaintythat is , the type of patients to whom clinicians would apply the test in the course of regular clinical practice . If studies fail this criterion ( e.g. , only enroll patients with severe disease and healthy controls ) , the apparent accuracy of a test is likely to be misleadingly high ( 8 , 9 ) . The second step shown in the Figure is , in most situations , based on judgments of test accuracy as a surrogate for patient-important outcomes . The key issue about these judgments is that they should be made transparent to those using the recommendations . For example , in the diagnosis of suspected acute urolithiasis , well- design ed studies demonstrate fewer false-negative results with noncontrast helical computed tomography ( CT ) than with intravenous pyelography ( IVP ) ( 10 ) . However , those ureteric stones that CT detects but IVP misses are smaller and therefore are more likely to spontaneously pass . Before r and omized trials evaluating outcomes in patients treated for smaller stones , evidence from observational studies was of lower quality . Thus , it remained uncertain how patients were affected by missed cases and follow-up of incidental findings unrelated to renal calculi with CT . Recommendations about using one test ( IVP ) over the other ( helical CT ) were based on judgments of how the cases that were detected or missed would fare with or without treatment ( 11 ) . These judgments were likely to be based on indirect evidence and would be less certain than judgments based on direct evidence from a r and omized trial comparing the 2 tests . The GRADE approach requires making these judgments about the relation between accuracy and patient-important outcomes transparent . The example of IVP versus helical CT for patients with suspected acute shows exemplifies how the quality of evidence for an accurate test would be down grade d because of the lack of direct evidence on patient-important outcomes . Uncertainty about patient-important consequences and associated uncertainty about benefits and harms would probably have result ed in weak GRADE recommendations about the use of IVP compared with helical CT . Those making recommendations using the GRADE approach should also explicitly consider judgments and evidence about the values and preferences that patients attach to important consequences , as described more fully elsewhere ( 1 ) . Acknowledgments : This work was partially funded by a The human factor , mobility and Marie Curie Actions Scientist Reintegration European Commission Grant ( IGR 42192 ) GRADE to Dr. Schnemann", "BACKGROUND Whether hypoglycemia leads to death in critically ill patients is unclear . METHODS We examined the associations between moderate and severe hypoglycemia ( blood glucose , 41 to 70 mg per deciliter [ 2.3 to 3.9 mmol per liter ] and ≤40 mg per deciliter [ 2.2 mmol per liter ] , respectively ) and death among 6026 critically ill patients in intensive care units ( ICUs ) . Patients were r and omly assigned to intensive or conventional glucose control . We used Cox regression analysis with adjustment for treatment assignment and for baseline and postr and omization covariates . RESULTS Follow-up data were available for 6026 patients : 2714 ( 45.0 % ) had moderate hypoglycemia , 2237 of whom ( 82.4 % ) were in the intensive-control group ( i.e. , 74.2 % of the 3013 patients in the group ) , and 223 patients ( 3.7 % ) had severe hypoglycemia , 208 of whom ( 93.3 % ) were in the intensive-control group ( i.e. , 6.9 % of the patients in this group ) . Of the 3089 patients who did not have hypoglycemia , 726 ( 23.5 % ) died , as compared with 774 of the 2714 with moderate hypoglycemia ( 28.5 % ) and 79 of the 223 with severe hypoglycemia ( 35.4 % ) . The adjusted hazard ratios for death among patients with moderate or severe hypoglycemia , as compared with those without hypoglycemia , were 1.41 ( 95 % confidence interval [ CI ] , 1.21 to 1.62 ; P The association with death was increased among patients who had moderate hypoglycemia on more than 1 day ( > 1 day vs. 1 day , P=0.01 ) , those who died from distributive ( vasodilated ) shock ( P absence of insulin treatment ( hazard ratio , 3.84 ; 95 % CI , 2.37 to 6.23 ; P critically ill patients , intensive glucose control leads to moderate and severe hypoglycemia , both of which are associated with an increased risk of death . The association exhibits a dose-response relationship and is strongest for death from distributive shock . However , these data can not prove a causal relationship . ( Funded by the Australian National Health and Medical Research Council and others ; NICE-SUGAR Clinical Trials.gov number , NCT00220987 . )", "BACKGROUND /st > In assessing a patient 's risk for postoperative nausea and vomiting ( PONV ) , it is important to know which risk factors are independent predictors , and which factors are not relevant for predicting PONV . METHODS /st > We conducted a systematic review of prospect i ve studies ( n>500 patients ) that applied multivariate logistic regression analyses to identify independent predictors of PONV . Odds ratios ( ORs ) of individual studies were pooled to calculate a more accurate overall point estimate for each predictor . RESULTS /st > We identified 22 studies ( n=95 154 ) . Female gender was the strongest patient-specific predictor ( OR 2.57 , 95 % confidence interval 2.32 - 2.84 ) , followed by the history of PONV/motion sickness ( 2.09 , 1.90 - 2.29 ) , non-smoking status ( 1.82 , 1.68 - 1.98 ) , history of motion sickness ( 1.77 , 1.55 - 2.04 ) , and age ( 0.88 per decade , 0.84 - 0.92 ) . The use of volatile anaesthetics was the strongest anaesthesia-related predictor ( 1.82 , 1.56 - 2.13 ) , followed by the duration of anaesthesia ( 1.46 h(-1 ) , 1.30 - 1.63 ) , postoperative opioid use ( 1.39 , 1.20 - 1.60 ) , and nitrous oxide ( 1.45 , 1.06 - 1.98 ) . Evidence for the effect of type of surgery is conflicting as reference groups differed widely and funnel plots suggested significant publication bias . Evidence for other potential risk factors was insufficient ( e.g. preoperative fasting ) or negative ( e.g. menstrual cycle ) . CONCLUSIONS /st > The most reliable independent predictors of PONV were female gender , history of PONV or motion sickness , non-smoker , younger age , duration of anaesthesia with volatile anaesthetics , and postoperative opioids . There is no or insufficient evidence for a number of commonly held factors , such as preoperative fasting , menstrual cycle , and surgery type , and using these factors may be counterproductive in assessing a patient 's risk for PONV", "Background and Aim : Immunomodulating nutrition is supposed to reduce the number of complications and lengthen of hospital stay during the postoperative period in patients after major gastrointestinal surgery . The aim of the study was to assess the clinical effect of immunostimulatory enteral and parenteral nutrition in patients undergoing resection for gastrointestinal cancer in the group of well-nourished patients . Material and Methods : Between June 1 , 2001 , and December 31 , 2005 , a group of 214 well-nourished patients was initially assessed ( 150 men , 64 women , mean age 61.2 years ) to participate in the study . Nine patients were subsequently excluded and the remaining 205 subjects were r and omly assigned in a 2 × 2 factorial design into 4 study groups , ie , st and ard enteral nutrition ( n = 53 ) , immunomodulating enteral nutrition ( n = 52 ) , st and ard parenteral nutrition ( n = 49 ) , and immunomodulating enteral nutrition ( n = 51 ) . The study was design ed to test the hypothesis that immunonutrition and enteral nutrition would reduce the incidence of infectious complications after upper gastrointestinal surgery ; the secondary objective of the study was to evaluate the effect of nutritional intervention on overall morbidity and mortality rates , and hospital stay . The study was registered in the Clinical Trials Data base – number NCT 00558155 . Results : The overall morbidity rate was 33 % and the incidence of individual complications was comparable between all groups . Infectious complications occurred in 26 of 102 patients given st and ard diets and in 22 of 103 patients receiving immunomodulatory formulas ( odds ratio 0.81 ; 95 % CI , 0.43–1.50 ) . There were no significant differences between infectious complications in patients using parenteral nutrition ( 22 of 100 patients ) and parenteral formulas ( 26 of 105 , odds ratio 1.14 ; 95 % CI , 0.61–2.14 ) . Neither immunostimulating formulas nor enteral feeding significantly affected secondary outcome measures , including overall morbidity and mortality rates , and hospital stay . Conclusions : Our study failed to demonstrate any clear advantage of routine postoperative immunonutrition in patients undergoing elective upper gastrointestinal surgery . Both enteral and parenteral treatment options showed similar efficacy , tolerance , and effects on protein synthesis . Parenteral nutrition composed according to contemporary rules showed similar efficiency to enteral nutrition . However , because of its cost-efficiency , enteral therapy should be considered as the treatment of choice in all patients requiring nutritional therapy", "BACKGROUND The efficacy of octreotide to prevent postoperative pancreatic fistula ( POPF ) of pancreaticoduodenectomy ( PD ) is still controversial . This study aim ed to evaluate the effect of postoperative use of octreotide on the outcomes after PD . METHODS This is a prospect i ve r and omized controlled trial for postoperative use of octreotide in patients undergoing PD . Patients with soft pancreas and pancreatic duct Group I did not receive postoperative octreotide . Group II received postoperative octreotide . The primary end of the study is to compare the rate of POPF . RESULTS A total of 104 patients were included in the study and were divided into two r and omized groups . There were no significant difference in overall complications and its severity . POPF occurred in 11 patients ( 21.2 % ) in group I and 10 ( 19.2 % ) in group II , without statistical significance ( P = 0.807 ) . Also , there was no significant differences between both groups regarding the incidence of biliary leakage ( P = 0.083 ) , delayed gastric emptying ( P = 0.472 ) , and early postoperative mortality ( P = 0.727 ) . CONCLUSIONS Octreotide did not reduce postoperative morbidities , reoperation and mortality rate . Also , it did not affect the incidence of POPF and its clinical ly relevant variants", "Purpose The purpose of this study was to evaluate the effects of preoperative forced-air warming on intraoperative hypothermia . Methods In this r and omized-controlled trial , adult patients scheduled for elective , non-cardiac surgery under general anesthesia were stratified by scheduled surgical duration ( and then r and omized to a pre-warming group using a BairPaws ™ forced-air warming system for at least 30 min preoperatively or to a control group with warmed blankets on request . All patients were warmed intraoperatively via convective forced-air warming blankets . Perioperative temperature was measured using the SpotOn ™ temperature system consisting of a single-use disposable sensor applied to the participant ’s forehead . The primary outcome was the magnitude of intraoperative hypothermia calculated as the area under the time-temperature curve for core temperatures included surgical site infections , packed red blood cell requirements , and 24 hr postoperative opioid consumption . Results Two hundred participants were analyzed ( 101 control ; 99 pre-warmed ) . Pre-warmed participants had a lower median [ interquartile range ] magnitude of hypothermia than controls ( 0.00 [ 0.00 - 0.12 ] ° C·hr−1vs 0.05 [ 0.00 - 0.36 ] ° C·hr−1 , respectively ; median difference , −0.01 ° C·hr−1 ; 95 % confidence interval , −0.04 to 0.00 ° C·hr−1 ; P = 0.005 ) . There were no between-group differences in the secondary outcomes . Conclusion A minimum of 30 min of preoperative forced-air convective warming decreased the overall intraoperative hypothermic exposure . While redistribution hypothermia still occurs despite pre- and intraoperative forced-air warming , their combined application results in greater preservation of intraoperative normothermia compared with intraoperative forced-air warming alone . Trial registration www . clinical trials.gov ( NCT02177903 ) . Registered 25 June 2014.RésuméObjectifL’objectif de cette étude était d’évaluer les conséquences du réchauffement préopératoire par air forcé sur l’hypothermie peropératoire . MéthodesDans cette étude r and omisée contrôlée , des patients adultes devant subir une chirurgie élective non cardiaque sous anesthésie générale ont été stratifiés en fonction de la durée prévue de l’intervention ( un système à air forcé BairPaws ™ pendant au moins 30 min en préopératoire ou dans un groupe témoin avec couvertures chauffantes sur dem and e. Tous les patients ont été réchauffés pendant l’intervention au moyen de couvertures chauffantes à air forcé par convection . La température périopératoire a été mesurée au moyen du système de surveillance de la température SpotOnMD consistant en un capteur jetable à usage unique placé sur le front des patients . Le critère principal d’évaluation était l’ampleur de l’hypothermie peropératoire calculée comme l’aire sous la courbe température-temps pour des températures central es infections du site chirurgical , le nombre de culots de globules rouges nécessaires et la consommation d’opioïdes au cours des 24 heures postopératoires . RésultatsLes résultats de 200 participants ont été analysés ( 101 contrôles ; 99 patients préréchauffés ) . L’amplitude médiane de l’hypothermie [ écart interquartile ] des participants préréchauffés a été plus faible que celle des contrôles ( respectivement , 0,00 [ 0,00 - 0,12 ] ° C·hr−1 contre 0,05 [ 0,00 - 0,36 ] ° C·hr−1 ; différence entre médianes , −0,01 ° C·hr−1 ; intervalle de confiance à 95 % , −0,04 à 0,00 ° C·hr−1 ; P réchauffement préopératoire au moyen d’un système à air forcé à convection a diminué l’exposition globale à l’hypothermie peropératoire . Bien qu’une hypothermie de redistribution survienne toujours en dépit du réchauffement peropératoire à l’air forcé , leur application combinée entraîne une meilleure conservation de la normothermie peropératoire , comparativement au réchauffement peropératoire à l’air forcé seul . Enregistrement de l’essai cliniquewww.essaiscliniques.gov ( NCT02177903 ) . Enregistré le 25 juin 2014", "Aims : To investigate whether preoperative enteral diets enriched in eicosapentaenoic acid ( EPA ) supplements could reduce the incidence of hypercytokinemia after pancreatoduodenectomy ( PD ) in a double-blinded r and omized controlled trial . Methods : Patients with resectable periampullary cancer were r and omized into either the control group or the treatment group . Patients in the treatment group received oral supplementation ( 600 kcal/day ) containing EPA for 7 days before surgery . Patients in the control group received isocaloric isonitrogenous st and ard nutrition ( 600 kcal/day ) without EPA for 7 days before surgery . The primary endpoint was postoperative serum concentrations of interleukin-6 ( IL-6 ) . The secondary endpoints were the postoperative nutritional status and the incidence of postoperative infectious complications . Results : Twenty-four patients were enrolled in the present study . After exclusion , 20 patients ( control group , n = 9 ; treatment group , n = 11 ) were analyzed . There were no significant differences in the curves for the serum concentration of IL-6 ( p = 0.68 ) or the incidence of infectious complications between the 2 groups ( control group : 78 % , treatment group : 55 % , p = 0.37 ) . Conclusions : The results of a double-blinded r and omized controlled trial indicated that preoperative immunonutrition had no marked impact on the rates of postoperative hypercytokinemia or infectious complications after PD", "Background : Postoperative nausea and vomiting ( PONV ) affects 20 % and 30 % of patients . As many as 60%–80 % patients at high risk may be affected . Dexamethasone ( D ) and midazolam ( M ) are well studied as antiemetic . Use of D can be associated with certain undesirable side effects so minimum dose is preferred . M is a routinely used premedicant . Hence , this study was design ed with both D and M in high risk patients for PONV to find minimum effective dose of D. Aims : To determine the minimum dose of D that combined with M would provide effective prophylaxis of PONV after laparoscopic cholecystectomy ( LC ) in patients at high risk for PONV . Setting and Design : This is a prospect i ve , r and omized double-blind trial . Material s and Methods : One hundred and fifty-five patients scheduled for elective LC were r and omized to 5 groups of 31 each . Group C was given normal saline , and the rest were administered D 1 mg ( group MD1 ) , 2 mg ( group MD2 ) , 4 mg ( group MD4 ) , or 8 mg ( group MD8 ) in combination with 0.04 mg/kg M at induction . The incidence of nausea , vomiting , severity of nausea , and the use of rescue antiemetic and postoperative pain was analyzed . Statistical Analysis : Chi-square test was used to compare incidence of study variables . Independent Student 's t-test was used for continuous variables . Demographic data were compared using ANOVA . P The incidence of nausea was significantly lower in group MD4 ( 29 % ) and MD8 ( 6 % ) compared to placebo group ( 71 % ) ( P vomiting was significantly lower in groups of MD2 ( 58 % ) , MD4 ( 48 % ) , and MD8 ( 6 % ) compared with placebo ( 90 % ) ( P reduction in nausea , pain severity , and incidence of use of rescue antiemetic in MD4 and MD8 groups with no discernable side effects of the drugs . Conclusion : We conclude that 4 mg D with M and 2 mg D with M is effective for prevention of nausea and vomiting , respectively , in patients at high risk for PONV undergoing LC", "Purpose : This study was to identify factors affecting postoperative nausea and vomiting ( PONV ) and to investigate the incidence of PONV for the first 24 hours after operation . Design : The prospect i ve research was performed in an 1,100‐bed university hospital , from April to December , 2011 . The sample consisted of 609 patients with elective surgery . Methods : Factors affecting PONV were identified by multiple logistic regression . Findings : Incidence of PONV was 27.1 % for the first postoperative 24 hours . Insertion of nasogastric tube ( OR , 4.54 , P = .002 ) , history of PONV ( OR , 3.24 , P motion sickness ( OR , 2.33 , P PONV . The nonadministration of antiemetics during operation ( OR , 1.70 , P = .014 ) and nonuse of intravenous patient‐controlled analgesia ( OR , 1.54 , P = .038 ) increased PONV during the first postoperative 24 hours . Conclusions : Patients of female gender , history of motion sickness and PONV , general anesthesia , and nasogastric insertion are more likely to experience PONV ", "Objective : To compare perioperative outcomes of pancreatoduodenectomy ( PD ) performed through the laparoscopic route or by open surgery . Summary Background Data : Laparoscopic PD is being progressively performed in selected patients . Methods : An open-label single-center RCT was conducted between February 2013 and September 2017 . The primary endpoint was the length of hospital stay ( LOS ) . Secondary endpoints were operative time , transfusion requirements , specific pancreatic complications ( pancreatic or biliary fistula , pancreatic hemorrhage , and delayed gastric emptying ) , Clavien – Dindo grade ≥ 3 complications , comprehensive complication index ( CCI ) score , poor quality outcome ( PQO ) , and the quality of pathologic resection . Analyses were performed on an intention to treat basis . Results : Of 86 patients assessed for PD , 66 were r and omized ( 34 laparoscopic approach , 32 open surgery ) . Conversion to an open procedure was needed in 8 ( 23.5 % ) patients . Laparoscopic versus open PD was associated with a significantly shorter LOS ( median 13.5 vs. 17 d ; P = 0.024 ) and longer median operative time ( 486 vs. 365 min ; P = 0.0001 ) . The laparoscopic approach was associated with significantly better outcomes regarding Clavien – Dindo grade ≥ 3 complications ( 5 vs. 11 patients ; P = 0.04 ) , CCI score ( 20.6 vs. 29.6 ; P = 0.038 ) , and PQO ( 10 vs. 14 patients ; P = 0.041 ) . No significant differences in transfusion requirements , pancreas-specific complications , the number of lymph nodes retrieved , and resection margins between the two approaches were found . Conclusions : Laparoscopic PD versus open surgery is associated with a shorter LOS and a more favorable postoperative course while maintaining oncological st and ards of a curative-intent surgical resection . Trial registry : IS RCT N93168938", "BACKGROUND Laparoscopic pancreatoduodenectomy may improve postoperative recovery compared with open pancreatoduodenectomy . However , there are concerns that the extensive learning curve of this complex procedure could increase the risk of complications . We aim ed to assess whether laparoscopic pancreatoduodenectomy could reduce time to functional recovery compared with open pancreatoduodenectomy . METHODS This multicentre , patient-blinded , parallel-group , r and omised controlled phase 2/3 trial was performed in four centres in the Netherl and s that each do 20 or more pancreatoduodenectomies annually ; surgeons had to have completed a dedicated training programme for laparoscopic pancreatoduodenectomy and have done 20 or more laparoscopic pancreatoduodenectomies before trial participation . Patients with a benign , premalignant , or malignant indication for pancreatoduodenectomy , without signs of vascular involvement , were r and omly assigned ( 1:1 ) to undergo either laparoscopic or open pancreatoduodenectomy using a central web-based system . R and omisation was stratified for annual case volume and preoperative estimated risk of pancreatic fistula . Patients were blinded to treatment allocation . Analysis was done according to the intention-to-treat principle . The main objective of the phase 2 part of the trial was to assess the safety of laparoscopic pancreatoduodenectomy ( complications and mortality ) , and the primary outcome of phase 3 was time to functional recovery in days , defined as all of the following : adequate pain control with only oral analgesia ; independent mobility ; ability to maintain more than 50 % of the daily required caloric intake ; no need for intravenous fluid administration ; and no signs of infection ( temperature Between May 13 and Dec 20 , 2016 , 42 patients were r and omised in the phase 2 part of the trial . Two patients did not receive surgery and were excluded from analyses in accordance with the study protocol . Three ( 15 % ) of 20 patients died within 90 days after laparoscopic pancreatoduodenectomy , compared with none of 20 patients after open pancreatoduodenectomy . Based on safety data from the phase 2 part of the trial , the data and safety monitoring board and protocol committee agreed to proceed with phase 3 . Between Jan 31 and Nov 14 , 2017 , 63 additional patients were r and omised in phase 3 of the trial . Four patients did not receive surgery and were excluded from analyses in accordance with the study protocol . After r and omisation of 105 patients ( combining patients from both phase 2 and phase 3 ) , of whom 99 underwent surgery , the trial was prematurely terminated by the data and safety monitoring board because of a difference in 90-day complication-related mortality ( five [ 10 % ] of 50 patients in the laparoscopic pancreatoduodenectomy group vs one [ 2 % ] of 49 in the open pancreatoduodenectomy group ; risk ratio [ RR ] 4·90 [ 95 % CI 0·59 - 40·44 ] ; p=0·20 ) . Median time to functional recovery was 10 days ( 95 % CI 5 - 15 ) after laparoscopic pancreatoduodenectomy versus 8 days ( 95 % CI 7 - 9 ) after open pancreatoduodenectomy ( log-rank p=0·80 ) . Clavien-Dindo grade III or higher complications ( 25 [ 50 % ] of 50 patients after laparoscopic pancreatoduodenectomy vs 19 [ 39 % ] of 49 after open pancreatoduodenectomy ; RR 1·29 [ 95 % CI 0·82 - 2·02 ] ; p=0·26 ) and grade B/C postoperative pancreatic fistulas ( 14 [ 28 % ] vs 12 [ 24 % ] ; RR 1·14 [ 95 % CI 0·59 - 2·22 ] ; p=0·69 ) were comparable between groups . INTERPRETATION Although not statistically significant , laparoscopic pancreatoduodenectomy was associated with more complication-related deaths than was open pancreatoduodenectomy , and there was no difference between groups in time to functional recovery . These safety concerns were unexpected and worrisome , especially in the setting of trained surgeons working in centres performing 20 or more pancreatoduodenectomies annually . Experience , learning curve , and annual volume might have influenced the outcomes ; future research should focus on these issues . FUNDING Grant for investigator-initiated studies by Johnson & Johnson Medical Limited", "BACKGROUND Intraoperative hypothermia is a common event during laparoscopic abdominal surgery . On one h and , intraoperative hypothermia can delay the metabolism and prevent tissue damage . One the other h and , long-term and severe intraoperative hypothermia may also lead to perioperative complications , such as increasing of peripheral resistance , coagulation dysfunction , intraoperative hemorrhage and postoperative shivering . Maintenance of normothermia during surgical procedures may improve the quality of patient care . OBJECTIVES This study investigated the feasibility and efficacy of intraoperative cutaneous warming with an underbody warming system during laparoscopic gastrointestinal surgery . METHODS 110 patients undergoing laparoscopic surgery for gastrointestinal cancer between January and December 2011 were r and omized into the laparoscopic control ( Control ) group and laparoscopic intervention ( Intervention ) group . Nasopharyngeal temperature , prothrombin time , activated partial thromboplastin time , and thrombin time were measured before and during surgery , intraoperative and postoperative complications , as well as shivering after anesthesia and visual analog scale score for pain evaluation after surgery were also recorded . Clinical risk factors that may cause intraoperative hypothermia during laparoscopic surgery were also analyzed by correlation analysis . RESULTS The two groups were comparable at the baseline . Intraoperative hypothermia was observed in 29 patients ( 52.7 % ) in Control group and 3 ( 5.5 % ) in Intervention group . Nasopharyngeal temperature in Control group was significantly decreased since 30min after the start of operation until the end of surgery comparing to that at the start of anesthesia , but there was no difference in the Intervention group . In Intervention group , the nasopharyngeal temperature was remaining at ∼36.5 ° C , indicating the feasibility and efficiency of the underbody warming system in preventing intraoperative hypothermia during laparoscopic gastrointestinal surgery . Moreover , with anesthesia and operation time increased , there was no significant change of coagulation function , hemoglobin level as well as less intraoperative hemorrhage , less postoperative shivering and lower visual analog scale score in Intervention group comparing to Control group . Multivariate logistic regression analysis revealed that anesthesia time and volume of CO2 were independent risk factors for perioperative hypothermia . CONCLUSIONS Cutaneous warming with an underbody warming system is a feasible and effective method to prevent intraoperative hypothermia during laparoscopic gastrointestinal surgery", "BACKGROUND Most surgeons routinely place a nasogastric tube at the time of a pancreatic resection . The goal of the present study was to evaluate the outcome when a pancreatic resection is performed without routine post-operative nasogastric suction . METHODS One hundred consecutive patients underwent a pancreatic resection ( 64 a pancreaticoduodenectomy , 98 % pylorus sparing and 36 a distal pancreatectomy ) . In the first cohort ( 50 patients ) , a nasogastric tube was routinely placed at the time of surgery and in the second cohort ( 50 patients ) the nasogastric was removed in the operating room . Outcomes for these two cohorts were recorded in a prospect i ve data base and compared using the χ(2 ) or Fisher 's exact test and Wilcoxon 's rank-sum test . RESULTS Demographical , surgical and pathological details were similar between the two cohorts . A post-operative complication occurred in 22 ( 44 % ) in each group ( P= 1.000 ) . There were no statistically significant differences in the frequency or severity of complications , or length of stay between groups . The spectrum of complications experienced by the two cohorts was similar including complications that could potentially be related to the use of nasogastric suction such as delayed gastric emptying , anastomotic leak , wound dehiscence and pneumonia . There was no difference between the two groups in the number of patients who required post-operative nasogastric tube placement ( or replacement ) [ 2 ( 4 % ) vs. 4 ( 8 % ) , P= 0.678 ] . CONCLUSION It may be safe to place a nasogastric tube post-operatively in a minority of patients after a pancreatic resection and spare the majority the discomfort associated with routine post-operative nasogastric suction ", "BACKGROUND Pasireotide is a newer generation somatostatin analogue that led to a significant reduction in pancreatic fistula after pancreatectomy in a single-center r and omized controlled trial . We sought to determine if pasireotide reduces the incidence of pancreatic fistula and other complications after pancreaticoduodenectomy at our high volume center . STUDY DESIGN All patients undergoing pancreaticoduodenectomy between April 2011 and January 2017 were prospect ively followed , and their complications were grade d using the Modified Accordion Grading System ( MAGS ) in our institutional complications data base . For 18 months , 5 pancreatic surgeons used pasireotide routinely in patients undergoing pancreaticoduodenectomy . Patients receiving pasireotide were then propensity score-matched to patients who did not receive pasireotide , and their outcomes were compared . RESULTS There were 459 patients who underwent pancreaticoduodenectomy , and 127 patients ( 28 % ) received pasireotide . Patients who received pasireotide were significantly more likely to have dilated pancreatic ducts and have a drain left at the time of surgery . Patients who received pasireotide had no difference in pancreatic fistula , overall complications , 90-day readmission , or 90-day mortality . However , patients who received pasireotide had a significantly reduced rate of postoperative bleeding/anemia ( 8.7 % vs 16.9 % , p = 0.03 ) . Among 112 propensity score-matched pairs , patients who received pasireotide did not have significantly different rates of pancreatic fistula , and the rates of severe ( MAGS grade s 3 to 6 ) pancreatic fistula were identical between the 2 groups ( 7.1 % vs 7.1 % , p = 1.00 ) . Matched patients who received pasireotide had significantly decreased postoperative bleeding/anemia ( 9.8 % vs 19.6 % , p = 0.04 ) . CONCLUSIONS Pasireotide did not reduce the incidence or severity of pancreatic fistulas after pancreaticoduodenectomy , but was associated with a decrease in postoperative bleeding/anemia . A multicenter r and omized trial is needed to accurately define the role of pasireotide in the postoperative management of pancreaticoduodenectomy patients", "Background Protocol s for enhanced recovery provide comprehensive and evidence -based guidelines for best perioperative care . Protocol implementation may reduce complication rates and enhance functional recovery and , as a result of this , also reduce length-of-stay in hospital . There is no comprehensive framework available for pancreaticoduodenectomy . Methods An international working group constructed within the Enhanced Recovery After Surgery ( ERAS ® ) Society constructed a comprehensive and evidence -based framework for best perioperative care for pancreaticoduodenectomy patients . Data were retrieved from st and ard data bases and personal archives . Evidence and recommendations were classified according to the GRADE system and reached through consensus in the group . The quality of evidence was rated “ high ” , “ moderate ” , “ low ” or “ very low ” . Recommendations were grade d as “ strong ” or “ weak ” . Results Comprehensive guidelines are presented . Available evidence is summarised and recommendations given for 27 care items . The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations . Conclusions The present evidence -based guidelines provide the necessary platform upon which to base a unified protocol for perioperative care for pancreaticoduodenectomy . A unified protocol allows for comparison between centres and across national borders . It facilitates multi-institutional prospect i ve cohort registries and adequately powered r and omised trials", "AIMS To evaluate the impact of prophylactic octreotide on gastric emptying in patients undergoing pancreaticoduodenectomy . Postoperative pancreatic fistula ( POPF ) and delayed gastric emptying ( DGE ) are common complications after pancreaticoduodenectomy . Whereas several prospect i ve r and omized trials propose the prophylactic use of octreotide to prevent pancreatic fistula formation , somatostatin has , however , been associated with delayed gastric emptying after partial duodenopancreatectomy . METHODS In this prospect i ve , r and omized , double-blinded , placebo-controlled trial we analyzed the influence of prophylactic octreotide on delayed gastric empting after pancreaticoduodenectomy . Patients were r and omized to the placebo group ( n=32 ) and the octreotide group ( n=35 ) . Primary endpoint was the incidence of delayed gastric emptying , secondary endpoints included perioperative morbidity other than DGE . DGE was measured by clinical signs , gastric scintigraphy and the hydrogen breath test . Risk factors for DGE other than octreotide were analyzed by univariate and multivariate analyses . RESULTS DGE measured by clinical signs was similar between both groups studied ( approximately 20 % of the patients ) . Gastric scintigraphy ( T(1/2 ) ) was 76.3+/-15.2 min in the octreotide group and 86.7+/-18.0 min in controls at day 7 , respectively . The H(2 ) breath test was 65.0+/-6.5 min in octreotide treatment group and 67.0+/-5.7 min in controls at day 8 . POPF grade C occurred in approximately 3 % of the patients , although prophylactic treatment of octreotide did not reduce the incidence of POPF . Multivariate analysis showed that postoperative intraabdominal bleeding and infection were independent risk factors for DGE . Furthermore preoperative biliary stenting reduced postoperative DGE after partial duodenopancreatectomy . CONCLUSION Prophylactic octreotide has no influence on gastric emptying and does not decrease the incidence of postoperative pancreatic fistula after pancreaticoduodenectomy" ]	411893d4-06ff-11f0-808a-c43d1ab1c353
Background Muscle power has been proposed to be the primary therapeutic target for resistance training interventions aim ed at enhancing physical function in older adults . However , no recommendations exist on ideal testing protocol s to assess muscle power in older adults , and the safety of this procedure has not been adequately evaluated in the literature . Methods A systematic review was conducted to identify studies evaluating muscle power exerted by older people in resistance exercises through May 2017 . Information from muscle power testing protocol s regarding familiarization , warm-up , measuring instrument , exercise , intensity , volume , rest intervals , data collection , and analysis was collected , as well as that regarding adverse events . Reporting bias was evaluated according to the recommendations given by the Cochrane Collaboration group . Results From 65 studies that met inclusion criteria , 3,484 older subjects and 11,841 muscle power tests distributed in 6,105 testing sessions were identified . A full description of the different muscle power testing protocol s was conducted . In addition , a risk of adverse events of 0.15%-0.69 % ( one adverse event every 144 - 658 muscle power tests ) was found . However , adverse events were poorly reported , with most of the studies showing a high risk of reporting bias . Conclusions Major discrepancies were found in muscle power testing protocol s among studies . This might limit consensus on design ing optimal training programs to improve muscle power and physical function in older adults , and underst and ing the main mechanisms involved in the age-related loss of muscle power . Finally , muscle power testing was found to be safe in older people with a broad range of health and functional states	[ "Summary Fall prevention is a key strategy for reducing osteoporotic fractures . We investigated the association between vitamin D receptor ( VDR ) polymorphisms and reported falls in postmenopausal women . Bsm1 polymorphisms were associated with falls , balance and muscle power measurements . These results may explain some of the excess fracture risk associated with VDR in some studies . Introduction Fall prevention is a key strategy for reducing osteoporotic fractures . It has been suggested that vitamin D supplementation may reduce the incidence of falls by reducing body sway and increasing muscle power . The vitamin D receptor gene is a well-studied c and i date gene for osteoporosis . We investigated the association between VDR polymorphisms and reported falls in postmenopausal women . Methods Falls data were collected in two separate population cohorts . Five polymorphisms of the VDR gene were analysed ( Cdx-2 , Fok-1 , BsmI , Taq1 and Apa1 ) in the Aberdeen Prospect i ve Osteoporosis Screening Study ( APOSS ) cohort . Results found in APOSS were then vali date d in an independent cohort — the Osteoporosis and Ultrasound ( OPUS ) study ( Bsm1 and Fok1 only ) , where muscle power and balance were also measured . Results Carriers of the ‘ B ’ allele ( Bsm1 ) showed an increased risk for falls . In APOSS , this was statistically significant for visit 3 multiple falls ( p = 0.047 ) and for recurrent falls ( p = 0.043 ) . Similar results were found in OPUS for visit 1 falls ( p = 0.025 ) and visit 1 multiple falls ( p = 0.015 ) . Bsm1 polymorphisms were also associated with balance and muscle power measurements . Conclusions In conclusion , these results demonstrate an association between the Bsm1 polymorphism and risk of falling that may explain some of the excess fracture risk associated with VDR in some studies", "OBJECTIVE To test the efficacy of high-velocity training in healthy older persons . DESIGN A 12-week r and omized trial , with subjects blocked for gender and residence , comparing high-velocity resistance training with a self-paced walking program . SETTING Retirement community . PARTICIPANTS Forty-three volunteers over the age of 70 years . INTERVENTION Power group : high-velocity leg exercises 3 times weekly with weekly increases in resistance combined with 45 minutes of moderate , nonresistance exercise weekly . Walking group : moderate intensity exercise 30 minutes daily , 6 days weekly . MAIN OUTCOME MEASURES Variables measured included leg press peak power and leg extensor strength . Functional performance outcomes included : 6-minute walk distance , Short Physical Performance Battery , Physical Performance Test , and Medical Outcomes Study Short-Form Health Survey . RESULTS Peak power improved 22 % ( p = .004 ) in the power group ( 3.7 + /- 1.0 W/kg to 4.5 + /- 1.4 W/kg ) but did not change in the walking group ( 3.99 + /-.76 W/kg to 3.65 + /-.94 W/kg ) . Leg extensor power at resistance of 50 % , 60 % , and 70 % of body weight increased 50 % , 77 % , and 141 % , respectively , in the power group ( p Strength improved 22 % in the power-trained individuals and 12 % in the walkers ( p functional task performance in either group . One subject developed a radiculopathy during training . CONCLUSIONS Resistance training focusing on speed of movement improved leg power and maximal strength substantially , but did not improve functional performance in healthy high-functioning older volunteers", "Sayers , SP and Gibson , K. A comparison of high-speed power training and traditional slow-speed resistance training in older men and women . J Strength Cond Res 24(12 ) : 3369 - 3380 , 2010-Muscle power , the product of force × velocity , is a critical determinant of function in older adults . Resistance training ( RT ) at high speed has been shown to improve peak muscle power in this population ; however , different functional tasks may benefit from the improvement of power at values other than “ peak ” values , for example , tasks that require a greater velocity component or a greater force component . This study compared the effect of high-speed RT on muscle performance ( peak power [ PP ] and its components [ PP force and PP velocity ] and overall peak velocity [ VEL ] ) across a broad range of external resistances . Thirty-eight older men and women were r and omized to high-speed power training at 40 % of the 1-repetition maximum ( 1RM ) ( n = 13 [ 74.1 ± 6.4 years ] ) ; traditional RT at 80 % 1RM ( n = 13 [ 70.1 ± 7.0 years ] ) ; or control ( n = 12 [ 72.8 ± 4.1 years ] ) . Measures of muscle performance were obtained at baseline and after the 12-week training intervention . Muscle power and 1RM strength improved similarly with both high-speed and traditional slow-speed RT . However , speed-related muscle performance characteristics , PP velocity and overall VEL , were most positively impacted by high-speed power training , especially at lower external resistances . Because gains in speed-related measures with high-speed training compared to traditional RT do not come at the expense of other muscle performance outcomes , we recommend using an RT protocol in older adults that emphasizes high-speed movements at low external resistances", "We examined whether high-speed power training ( HSPT ) improved muscle performance and braking speed using a driving simulator . 72 older adults ( 22 m , 50 f ; age = 70.6 ± 7.3 yrs ) were r and omized to HSPT at 40 % one-repetition maximum ( 1RM ) ( HSPT : n = 25 ; 3 sets of 12–14 repetitions ) , slow-speed strength training at 80%1RM ( SSST : n = 25 ; 3 sets of 8–10 repetitions ) , or control ( CON : n = 22 ; stretching ) 3 times/week for 12 weeks . Leg press and knee extension peak power , peak power velocity , peak power force/torque , and braking speed were obtained at baseline and 12 weeks . HSPT increased peak power and peak power velocity across a range of external resistances ( 40–90 % 1RM ; P and improved braking speed ( P Work was similar between groups , but perceived exertion was lower in HSPT ( P HSPT exerted a broader training effect and improved braking speed compared to SSST", "Background Slow gait is common in dementia , but it remains unknown whether the slowing happens many years prior to dementia onset . We therefore examined the relationship between slow baseline gait speed ( GS ) , change in GS , and the hazard of incident dementia in a community dwelling of elderly people . Methods A total of 3,663 participants dementia-free at baseline ( mean age , 73.5 years ) were followed up for 9 years from a prospect i ve cohort ( Three-City study , France ) for incident dementia ( all-cause , Alzheimer 's disease , vascular dementia , and other causes ) . GS over 6 m was assessed 4 times over the follow-up using two photoelectric cells . We used a multistate model to estimate the hazard ratio ( HR ) of dementia for baseline GS and tested a washout period of 4 to 7 years . The role of GS change between 65 and 85 years was examined using linear mixed models and joint models for survival and longitudinal data . Results A total of 296 participants developed dementia during the follow-up . In age/sex-adjusted models , 1-SD ( 0.204 m/s ) lower GS was associated with an increased hazard of dementia ( HR = 1.59 , 95 % confidence interval [ CI ] = 1.39 , 1.81 , p hazard of dementia ( HR per 1 SD [ 0.007 m/s/year ] decrease = 3.39 [ 1.37 - 8.43 ] , p = .009 ) . Conclusions Gait is slower up to 7 years prior to clinical onset of dementia . Decline in GS is also more accelerated , suggesting strong links between cognitive and motor function in older adults", "Context : Findings of studies of testosterone ’s effects on muscle strength and physical function in older men have been inconsistent ; its effects on muscle power and fatigability have not been studied . Objective : To determine the effects of testosterone administration for 3 years in older men on muscle strength , power , fatigability , and physical function . Design , Setting , and Participants : This was a double-blind , placebo-controlled , r and omized trial of healthy men ≥60 years old with total testosterone levels of 100 to 400 ng/dL or free testosterone levels Interventions : R and om assignment to 7.5 g of 1 % testosterone or placebo gel daily for 3 years . Outcome Measures : Loaded and unloaded stair-climbing power , muscle strength , power , and fatigability in leg press and chest press exercises , and lean mass at baseline , 6 , 18 , and 36 months . Results : The groups were similar at baseline . Testosterone administration for 3 years was associated with significantly greater performance in unloaded and loaded stair-climbing power than placebo ( mean estimated between-group difference , 10.7 W [ 95 % confidence interval ( CI ) , −4.0 to 25.5 ] , P = 0.026 ; and 22.4 W [ 95 % CI , 4.6 to 40.3 ] , P = 0.027 ) , respectively . Changes in chest-press strength ( estimated mean difference , 16.3 N ; 95 % CI , 5.5 to 27.1 ; P 0.001 ) and power ( mean difference 22.5 W ; 95 % CI , 7.5 to 37.5 ; P were significantly greater in men r and omized to testosterone than in those r and omized to placebo . Lean body mass significantly increased more in the testosterone group . Conclusion : Compared with placebo , testosterone replacement in older men for 3 years was associated with modest but significantly greater improvements in stair-climbing power , muscle mass , and power . Clinical meaningfulness of these treatment effects and their impact on disability in older adults with functional limitations remains to be studied", "BACKGROUND Muscle power ( force x velocity ) recedes at a faster rate than strength with age and may also be a stronger predictor of fall risk and functional decline . The optimal training paradigm for improving muscle power in older adults is not known , although some literature suggests high velocity , low load training is optimal in young adults . METHODS One hundred twelve healthy older adults ( 69 + /- 6 years ) were r and omly assigned to either explosive resistance training at 20 % ( G20 ) , 50 % ( G50 ) , or 80 % ( G80 ) one repetition maximum ( 1RM ) for 8 - 12 weeks or to a nontraining control group ( CON ) . Participants trained twice per week ( five exercises ; three sets of eight rapidly concentric and slow eccentric repetitions ) using pneumatic resistance machines . Repeated- measures analysis of variance and covariance ( ANOVA and ANCOVA ) were used to determine the effects of training . RESULTS Average peak power increased significantly and similarly in G80 ( 14 + /- 8 % ) , G50 ( 15 + /- 9 % ) , and G20 ( 14 + /- 6 % ) compared to CON ( 3 + /- 6 % ) ( p average strength ( r = .40 , p = .0009 ) and endurance ( r = .43 , p = .0005 ) . Average strength increased in G80 ( 20 + /- 7 % ) , G50 ( 16 + /- 7 % ) , and G20 ( 13 + /- 7 % ) compared to CON ( 4 + /- 4 % ) ( p Average muscle endurance increased in G80 ( 185 + /- 126 % , p Peak muscle power may be improved similarly using light , moderate , or heavy resistances , whereas there is a dose-response relationship between training intensity and muscle strength and endurance changes . Therefore , using heavy loads during explosive resistance training may be the most effective strategy to achieve simultaneous improvements in muscle strength , power , and endurance in older adults", "Improving muscle strength and power may mitigate the effects of sarcopenia , but it is unknown if this improves an older adult ’s ability to recover from a large postural perturbation . Forward tripping is prevalent in older adults and lateral falls are important due to risk of hip fracture . We used a forward and a lateral single-step balance recovery task to examine the effects of strength training ( ST ) or power ( PT ) training on single-step balance recovery in older adults . Twenty older adults ( 70.8±4.4 years , eleven male ) were r and omly assigned to either a 6-week ( three times/week ) lower extremity ST or PT intervention . Maximum forward ( FLeanmax ) and lateral ( LLeanmax ) lean angle and strength and power in knee extension and leg press were assessed at baseline and follow-up . Fifteen participants completed the study ( ST = 7 , PT = 8) . Least squares means ( 95 % CI ) for ΔFLeanmax ( ST : + 4.1 ° [ 0.7 , 7.5 ] ; PT : + 0.6 ° [ −2.5 , 3.8 ] ) and ΔLLeanmax ( ST : + 2.2 ° [ 0.4 , 4.1 ] ; PT : + 2.6 ° [ 0.9 , 4.4 ] ) indicated no differences between groups following training . In exploratory post hoc analyses collapsed by group , ΔFLeanmax was + 2.4 ° ( 0.1 , 4.7 ) and ΔLLeanmax was + 2.4 ° ( 1.2 , 3.6 ) . These improvements on the balance recovery tasks ranged from ~15%–30 % . The results of this preliminary study suggest that resistance training may improve balance recovery performance , and that , in this small sample , PT did not lead to larger improvements in single-step balance recovery compared to ST", "Fighting against inactivity and inadequate nutritional intake are of utmost importance in the elderly . To our knowledge , the few studies which have been performed were conducted for only a short period and the results do not permit formal conclusions to be drawn . We therefore tried to fill this gap in our knowledge by determining whether an intervention combining an acceptable progressive exercise programme and nutritional supplements would be feasible for a long-term period in the very frail elderly , and would bring about concomitant benefits in body composition and muscle power . Accordingly , this exercise and nutritional combination was assessed in the frail elderly in a 9-month r and omised trial with a factorial design . Fifty-seven elderly volunteers over 72 years , from sixteen retirement homes in Lyon , France participated in the study . Dietary supplements were compared with placebo , and physical exercise was compared with memory training . Main outcome measures were fat-free mass ( FFM ) and muscle power . FFM was determined by labelled water , and muscle power was measured by a leg-extensor machine . At 9 months , the compliance was 63 % for exercise sessions , and 54 % for nutritional supplements . In patients with dietary supplements , muscle power increased by 57 % at 3 months ( P=0.03 ) , and showed only a tendency at 9 months ; although FFM increased by 2.7 % at 9 months , the difference was not significant ( P=0.10 ) . Exercise did not improve muscle power at 9 months , but improved functional tests ( five-time-chair rise , P=0.01 ) . BMI increased with supplements ( + 3.65 % ) , but decreased with placebo ( -0.5 % ) at 9 months ( P=0.007 ) . A long-term combined intervention is feasible in frail elderly individuals with a good rate of compliance . Nutritional supplements and exercise may improve muscle function . Despite no significant results on FFM , due to the limited number of volunteers , combined intervention should be suggested to counteract muscle weakness in the frail elderly", "OBJECTIVE To test which rehabilitative impairments are associated with higher mobility performance among community-dwelling , mobility-limited older adults . DESIGN Cross-sectional analysis of baseline data from participants within a r and omized controlled trial . SETTING Outpatient rehabilitation research center . PARTICIPANTS Community-dwelling older adults ( N=138 ; mean age , 75.4 y ) with mobility limitations as defined by the Short Physical Performance Battery ( SPPB ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Balance measured via the Berg Balance Scale , leg strength , leg velocity , submaximal aerobic capacity , body mass index ( BMI ) , and mobility performance as measured by the SPPB . RESULTS Each of the 5 physiologic attributes ( unipedal balance , leg strength , leg velocity , submaximal aerobic capacity , BMI ) was categorized into tertiles by using lower values as reference for impairment status . Within an adjusted model , measures associated with higher SPPB performance ( > 9 ) included a BBS score greater than or equal to 54 ( odds ratio [OR]=4.54 ; 95 % confidence interval [ CI ] , 1.11 - 18.60 ) , leg strength greater than or equal to 21.5 N/kg ( OR=30.35 ; 95 % CI , 5.48 - 168.09 ) , leg velocity .0101 to .0129 m.s(-1).kg(-1 ) ( OR=5.31 ; 95 % CI , 1.25 - 22.57 ) , and leg velocity greater than or equal to .0130 m.s(-1).kg(-1 ) ( OR=22.86 ; 95 % CI , 3.88 - 134.75 ) . CONCLUSIONS Our investigation highlights the importance of rehabilitative impairments in leg strength , leg velocity , and balance as being associated with mobility status as measured by the SPPB . In our sample of participants within an exercise trial , submaximal aerobic capacity and BMI status were not associated with mobility performance . These findings suggest that the augmentation of not only leg strength and balance but also leg velocity may be important in the rehabilitative care of mobility-limited older adults", "OBJECTIVE To determine the effect of training intensity on the contributions of force and velocity to improvements in peak power ( PP ) after explosive resistance training in older adults . METHODS 112 healthy older adults ( 69 + /- 6 yr ) were r and omized to explosive resistance training at 20 % ( G20 ) , 50 % ( G50 ) , or 80 % ( G80 ) maximal strength ( 1-repetition maximum ) for 8 - 12 wk ( twice weekly , 5 exercises , 3 sets of 8 explosive concentric/slow eccentric repetitions ) using pneumatic resistance machines or a nontraining control group ( CON ) . RESULTS Force at peak power ( FPP ) increased significantly and similarly among training groups compared with CON . Velocity at peak power ( VPP ) did not improve significantly and remained similar between all groups . Force contributed significantly more to PP production in G80 and G50 than in CON . The change in PP was independently predicted by changes in fat-free mass in G80 and by changes in both FPP and VPP in G50 and G20 . CONCLUSION Explosive resistance training in older adults results in the ability to produce higher PP outputs with heavier loads without loss of movement velocity . Moderate- to high-intensity training induced a greater relative contribution of force to PP production in this cohort", "To determine whether 10 weeks of whole-body vibration ( WBV ) training has a significant effect on strength , muscle mass , muscle power , and mobility in older women , 26 subjects were r and omly assigned to a WBV training group ( n=13 ; mean age 79 years ) and a control ( CON ) group ( n=13 ; mean age 76 years ) . Maximal voluntary isometric contraction ( MVIC ) increased 38.8 % in the WBV group , without changes in the CON group . Electromyographic activity of the vastus medialis ( VM ) , the vastus lateralis , and the biceps femoris ( BF ) did not change in either group . Thigh muscle cross-sectional area increased significantly after training in VM ( 8.7 % ) and BF ( 15.5 % ) . Muscle power at 20 % , 40 % , and 60 % MVIC decreased from pre-test to post-test in the CON group ; however , WBV training prevented the decrease in the WBV group . Consequently , mobility , measured by the Timed Up and Go test , increased significantly after training ( 9.0 % ) only in the WBV group . Ten weeks of lower limb WBV training in older women produces a significant increase in muscle strength induced by thigh muscle hypertrophy , with no change in muscle power . The adaptations to WBV found in the present study may be of use in counteracting the loss of muscle strength and mobility associated with age-induced sarcopenia", "The purpose s of this study were to examine age and gender differences in knee extensor strength , power , and fatigue using open- and closed-chain testing procedures . We tested the hypothesis that specific strength ( strength/unit muscle mass ) would not differ by age , whereas age differences in specific power and fatigue would remain consequent to blunted maximal contractile velocity . Skeletal muscle performance was examined in 28 young ( 26.9 + /- 0.7 yr ) and 24 older ( 63.6 + /- 0.8 yr ) men and women . Assessment s included one-repetition maximum strength for knee extension , leg press , and squat ; concentric knee extensor peak power , velocity , and fatigability ; and sit-to-st and power , fatigability , and relative neural activation ( electromyograph activity during sit-to-st and movement normalized to electromyograph activity during isometric maximum voluntary contraction ) . Thigh lean mass ( TLM ; kg ) was assessed by dual-energy X-ray absorptiometry . Specific strength ( N/kg TLM ) and specific power ( W/kg TLM ) were estimated by dividing absolute values by TLM . Age differences in specific strength were observed for knee extension only ( young , 41.2 + /- 1.0 N/kg TLM ; older , 32.4 + /- 1.0 N/kg TLM ; P knee extension specific power ( 25 - 41 % lower in older ; P fatigue across 10 repetitions of knee extension as peak velocity fell by 24 % ( P concentric power persist after adjustment for TLM as maximum contractile velocity falls markedly with aging . Older adults are less capable of sustaining maximum concentric velocity during repetitive contractions . These findings suggest that velocity impairments are a possible contributor to mobility loss and falls risk among older adults . Interventions for improving contractile velocity should be pursued", "PURPOSE A decrease in strength , and its associated loss of functional ability is common among the elderly . Although resistance training can reverse this decline , associated injuries with frequently used strength assessment s may present a greater risk . METHODS To evaluate the injuries associated with maximal strength evaluations , 83 relatively healthy elderly subjects ( 40 men and 43 women , 65.8 + /- 6.2 years ) with and without prior weight training experience performed 1 repetition maximum testing ( 1 RM ) involving 5 different exercises : chest press , leg extension , abdominal curl , arm curl , and seated calf raise . Subjects were separated into three groups depending on weight training experience , Group 1 had no weight training experience ( n = 32 ) , Group 2 had months of training ( n = 24 ) , and Group 3 had > 6 months of training ( n = 27 ) . Injury assessment was made 30 minutes , 2 days , and 7 days posttesting . RESULTS Two Group 1 subjects sustained an injury ( 2.4 % of total subjects , 8 % of Group 1 ) . Eighty-one subjects safely completed the 1 RM assessment without injury ( 97.6 % of total ) . Forty-eight of the 83 subjects complained of muscle soreness after testing ( 58 % of total ) . This complaint alone was not sufficient to be categorized as an injury . CONCLUSIONS These results indicate that 1 RM testing is an acceptable tool in strength evaluations in the elderly . Additional pre caution s may be needed in inexperienced , elderly individuals to prevent injury", "Background and aims : This study investigated whether high-velocity high-power training ( POW ) improved lower extremity muscle power and quality in functionally-limited elders greater than traditional slow-velocity progressive resistance training ( STR ) . Methods : Fifty-seven community-dwelling older adults aged 74.2±7 ( range 65–94 yrs ) , Short Physical Performance Battery score 7.7±1.4 , were r and omized to either POW ( n=23 ) ( 12 females ) , STR ( n=22 ) ( 13 females ) or a control group of lower extremity stretching ( CON ) ( n=12 ) ( 6 females ) . Training was performed three times per week for 12 weeks and subjects completed three sets of double leg press and knee extension exercises at 70 % of the one repetition maximum ( 1RM ) . Outcome measures included 1RM strength and peak power ( PP ) . Total leg lean mass was determined using dual-energy X-ray absorptiometry to estimate specific strength and specific PP . Results : During training , power output was consistently higher in POW compared to STR for knee extension ( ∼2.3-fold ) and leg press ( ∼2.8-fold ) exercises ( p this , PP and specific PP of the knee extensors increased similarly from baseline in POW and STR compared to CON ( p for PP of the leg extensors . However , gains in leg press specific PP were significantly greater in POW compared to both STR and CON ( p did not change within any group . Conclusions : A short-term intervention of high-velocity power training and traditional slow-velocity progressive resistance training yielded similar increases of lower extremity power in the mobility-impaired elderly . Neuromuscular adaptations to power training , rather than skeletal muscle hypertrophy , may have facilitated the improvements in muscle quality . Additional studies are warranted to test the efficacy of power training in older individuals with compromised physical functioning", "BACKGROUND We compared the effects of two uniquely different lower extremity power training interventions on changes in muscle power , physical performance , neuromuscular activation , and muscle cross sectional area in mobility-limited older adults . METHODS Fifty-two subjects ( 78±5 years , short physical performance battery score : 8.1±1 ) were r and omized to either 16 weeks of progressive high velocity resistance training performed at low external resistance ( 40 % of the 1-repetition maximum [ 1-RM ] [ LO ] ) or high external resistance ( 70 % of 1RM [ HI ] ) . Both groups completed three sets of leg and knee extension exercises at maximum voluntary velocity , two times per week . Neuromuscular activation was assessed using surface electromyography and muscle cross sectional area ( CSA ) was measured using computed tomography . RESULTS At 16 weeks , LO and HI exhibited significant and similar within-group increases of leg extensor peak power ( ~34 % vs ~42 % ) , strength ( ~13 % vs ~19 % ) , and SPPB score ( 1.4±0.3 vs 1.8±0.3 units ) , respectively ( all P ) . Improvements in neuromuscular activation occurred in LO ( P = .03 ) while small gains in mid-thigh muscle CSA were detected in LO ( 1.6 % , P = .35 ) and HI ( 2.1 % , P = .17 ) . No significant between-group differences were evident for any measured parameters ( all P > .25 ) . CONCLUSIONS High velocity resistance training with low external resistance yields similar improvements in muscle power and physical performance compared to training with high external resistance in mobility-limited elders . These findings may have important implication s for optimizing exercise interventions for older adults with mobility limitations", "BACKGROUND chronological age is widely used as a marker of frailty in clinical practice . However there can be wide variation in frailty between individuals of a similar age . Grip strength is a powerful predictor of disability , morbidity and mortality which has been used in a number of frailty scores but not as a single marker of frailty . OBJECTIVE to investigate the potential of grip strength as a single marker of frailty in older people of similar chronological age . DESIGN cross-sectional study with prospect i ve collection of mortality data . SETTING North Hertfordshire , UK . SUBJECTS 717 men and women , aged 64 - 74 , born and still living in North Hertfordshire , who took part in a previous study to investigate the relationship between size at birth and ageing processes in later life . METHODS the number of significant associations between grip strength and the ageing markers was compared with numbers between chronological age and the ageing markers . RESULTS in men , lower grip strength correlated significantly with ten ageing markers compared to chronological age which was significantly associated with seven . In women , there were six significant relationships for grip compared to three for age . The greater number of relationships between grip strength and ageing markers was not explained by the association between grip strength and age , and remained after adjustment for adult size . CONCLUSIONS grip strength was associated with more markers of frailty than chronological age within the narrow age range studied . Grip strength may prove a more useful single marker of frailty for older people of similar age than chronological age alone . Its validity in a clinical setting needs to be tested", "OBJECTIVES The purpose of this study was to assess the influence of leg power and leg strength on the physical performance of community-dwelling mobility-limited older people . DESIGN Cross-sectional analysis of baseline data from a 12-week r and omized controlled exercise-intervention study . SETTING Exercise laboratory within the Department of Health Science of an urban university . PARTICIPANTS Forty-five community-dwelling mobility-limited people ( 34 women , 11 men ) , aged 65 to 83 . MEASUREMENTS Health status , depression , cognition , physical activity , and falls efficacy ; physiological measures of lower extremity strength and power ; and measures of physical performance . RESULTS Through bivariate analyses , leg power was significantly associated with physical performance as measured by stair-climb time , chair-st and time , t and em gait , habitual gait , maximal gait , and the short physical performance battery describing between 12 % and 45 % of the variance ( R2 ) . Although leg power and leg strength were greatly correlated ( r = .89 ) in a comparison of bivariate analyses of strength or power with physical performance , leg power modeled up to 8 % more of the variance for five of six physical performance measures . Despite limitations in sample size , it appeared that , through quadratic modeling , the influence of leg power on physical performance was curvilinear . Using separate multivariate analyses , partial R2 values for leg power and leg strength were compared , demonstrating that leg power accounted for 2 % to 8 % more of the variance with all measures of physical performance . CONCLUSION Leg power is an important factor influencing the physical performance of mobility-limited older people . Although related to strength , it is a separate attribute that may exert a greater influence on physical performance . These findings have important implication s for clinicians practicing geriatric rehabilitation", "OBJECTIVES To evaluate a dynamic form of weighted vest exercise suitable for home use and design ed to enhance muscle power , balance , and mobility . DESIGN A single-blind , r and omized , controlled trial . SETTING Outpatient exercise research facility situated within an academic long-term care center . PARTICIPANTS Twenty-one community-dwelling women aged 70 and older with a Short Physical Performance Battery ( SPPB ) score between 4 and 10 ( out of 12 ) . INTERVENTIONS Subjects were r and omized into a progressive resistance-training program using weighted vests for resistance with exercises design ed to be specific to mobility tasks and have a component performed at the fastest possible velocity ( Increased Velocity Exercise Specific to Task ( InVEST ) , n=11 ) or a control exercise group ( control , n=10 ) , which performed slow-velocity , low-resistance exercise . Both groups exercised three times a week for 12 weeks . MEASUREMENTS Changes in muscle power , balance , and physical performance were compared . RESULTS In comparison to control group , InVEST group manifested significant improvements ( P leg power across measurements obtained at 75 % to 90 % of the one-repetition maximum . Both groups demonstrated significant improvements in chair st and and SPPB score from baseline , and the InVEST group showed significant improvements in gait speed and chair st and from baseline ( P chair st and time than control ( P leg power and chair rise in this population and is worthy of further investigation as a means of enhancing balance and mobility", "This r and omized controlled trial examined the effects of multicomponent training on muscle power output , muscle mass , and muscle tissue attenuation ; the risk of falls ; and functional outcomes in frail nonagenarians . Twenty-four elderly ( 91.9 ± 4.1 years old ) were r and omized into intervention or control group . The intervention group performed a twice-weekly , 12-week multicomponent exercise program composed of muscle power training ( 8–10 repetitions , 40–60 % of the one-repetition maximum ) combined with balance and gait retraining . Strength and power tests were performed on the upper and lower limbs . Gait velocity was assessed using the 5-m habitual gait and the time-up- and -go ( TUG ) tests with and without dual-task performance . Balance was assessed using the FICSIT-4 tests . The ability to rise from a chair test was assessed , and data on the incidence and risk of falls were assessed using question naires . Functional status was assessed before measurements with the Barthel Index . Midthigh lower extremity muscle mass and muscle fat infiltration were assessed using computed tomography . The intervention group showed significantly improved TUG with single and dual tasks , rise from a chair and balance performance ( P and a reduced incidence of falls . In addition , the intervention group showed enhanced muscle power and strength ( P the total and high-density muscle cross-sectional area in the intervention group . The control group significantly reduced strength and functional outcomes . Routine multicomponent exercise intervention should be prescribed to nonagenarians because overall physical outcomes are improved in this population", "PURPOSE To compare the effects of the 16-wk training period ( 2 d.wk(-1 ) ) of resistance training alone ( S ) , endurance training alone ( E ) , or combined resistance ( once weekly ) and endurance ( once weekly ) training ( SE ) on muscle mass , maximal strength and power of the leg and arm extensor muscles , and maximal workload ( Wmax ) by using a incremental cycling test in older men . METHODS Thirty-one healthy men ( 65 - 74 yr ) were divided into three treatment groups to train 2x wk(-1 ) for 16 wk : S ( N = 10 ) , E ( N = 11 ) , or SE ( N = 10 ; 1x wk(-1 ) S + 1x wk(-1 ) E ) . The subjects were tested at 8-wk intervals ( i.e. , weeks 8 and 16 ) . RESULTS There were no significant differences between S- and SE-induced muscle hypertrophy ( 11 % and 11 % ) and maximal strength ( 41 % and 38 % ) gains of the legs as well as between E- and SE-induced Wmax ( 28 % and 23 % ) gains . The increase in arm strength in S ( 36 % ) was greater than that recorded in SE ( 22 % ) and greater than that recorded in E ( 0 % ) . CONCLUSIONS Prolonged combined resistance and endurance training in older men seemed to lead to similar gains in muscle mass , maximal strength , and power of the legs as resistance training alone and to similar gains in maximal peak power output measured in an incremental cycling test as endurance training alone . These findings may have an effect on how resistance exercise is prescribed to older adults ", "BACKGROUND Loss of muscle power due to normal aging has greater functional impact than loss of strength alone . The present study compared two resistance training programs , one aim ed at enhancing muscle power and one at increasing muscle strength , on muscle function and functional performance in older adults . METHODS Sixty-seven healthy , independent older adults ( 65 - 84 years ) were r and omized to a high-velocity varied resistance ( HV ) , constant resistance ( ST ) , or nontraining control ( CO ) group . Participants trained twice weekly for 24 weeks using six exercises . Dynamic and isometric muscle strength , muscle power , movement velocity , muscle endurance , and a battery of functional performance tasks were assessed . Secondary outcomes included body composition , quality of life , and balance confidence . RESULTS Muscle strength increased significantly ( p Peak muscle power also increased with training ( p peak power was 50.5 + /- 4.1 % , 33.8 + /- 3.8 % , and -2.5 + /- 3.9 % in the HV , ST , and CO groups , respectively . Training also improved selected functional performance tasks in the HV and ST groups compared to controls ( p quality of life ( p = .018 ) . CONCLUSION Muscle power and muscle strength improved similarly using either resistance training protocol , and these changes were accompanied by improvements in several functional performance tasks . However , improvements in the HV group occurred with less total work performed per training session", "BACKGROUND Identification of the physiologic factors most relevant to functional independence in the elderly population is critical for the design of effective interventions . It has been suggested that muscle power may be more directly related to impaired physical performance than muscle strength in elderly persons . We tested the hypothesis that peak muscle power is closely associated with self-reported functional status in sedentary elderly community-dwelling women . METHODS We used baseline data that were collected as part of a 1-year r and omized controlled clinical trial of a combined program of strength , power , and endurance training in 80 elderly women ( mean age 74.8 + /- 5.0 years ) with 3.2 + /- 1.9 chronic diseases , selected for baseline functional impairment and /or falls . RESULTS Functional status at baseline was related in univariate analyses to physiologic capacity , habitual physical activity level , neuropsychological status , and medical diagnoses . Leg power had the strongest univariate correlation to self-reported functional status ( r = -.47 , p leg press power and habitual physical activity level were the only two factors that contributed independently to functional status ( r = .64 , p Leg power is a strong predictor of self-reported functional status in elderly women", "Concurrent training is an effective method for increasing skeletal muscle performance in aging individuals , but controversy exists as to whether chronic neuromuscular and functional adaptations are affected by the intra-session exercise sequence . Therefore the aim of this study was to evaluate the effect of concurrent endurance and power-like strength training exercise sequence on muscular and functional adaptations of older participants . Thirty-six healthy older men not engaged in systematic exercise training programs for at least 6 months were divided into a control group ( CON ; 65.8±5.3 years ) , or in the training groups : endurance-strength ( ES ; 63.2±3.3 years ) , or strength-endurance ( SE ; 67.1±6.1 years ) . Training groups underwent 12 weeks of concurrent endurance and power-like strength training , starting every exercise session with either endurance ( in ES ) or strength ( in SE ) exercises . Measurements included knee extension one repetition maximum ( 1RM ) , knee extension power , 30 second sit-to-st and test ( 30SS ) , maximum vastus lateralis surface electromyographic activity , and rectus femoris echo intensity ( RFEI ) . Significant increases in maximal strength ( ES + 18±11.3 % ; SE + 14.2±6.0 % ; p≤0.05 ) , peak power ( ES + 22.2±19.4 % ; SE + 26.3±31.3 % ; p≤0.05 ) , and 30SS performance ( ES + 15.2±7.2 % ; SE + 13.2±11.8 % ; p≤0.05 ) were observed only in the training groups , with no differences between ES and SE . Maximum muscular activity was greater after 12weeks at training groups ( p≤0.05 ) , and reductions in RFEI were found only in ES and SE ( p≤0.05 ) . These results demonstrate that concurrent strength and endurance training performed twice a week effectively increases muscular performance and functional capacity in older men , independent of the intra-session exercise sequence . Additionally , the RFEI decreases indicate an additional adaptation to concurrent training", "OBJECTIVES From among physiological attributes commonly targeted in rehabilitation , to identify those in which changes led to clinical ly meaningful differences ( CMDs ) in mobility outcomes . DESIGN Secondary analysis of data collected for a r and omized controlled trial of exercise using binary outcomes defined by recording a large CMD ( Short Physical Performance Battery (SPPB)=1 unit ; gait speed (GS)=0.1 m/s ) . Iterative models were performed to evaluate possible confounding between physiological variables and relevant covariates . SETTING Outpatient rehabilitation centers . PARTICIPANTS Community-dwelling mobility-limited older adults ( n=116 ) participating in a 16-week r and omized controlled trial of two modes of exercise . MEASUREMENTS Physiological measures included leg power , leg strength , balance as measured according to the Performance-Oriented Mobility Assessment ( POMA ) , and rate pressure product at the maximal stage of an exercise tolerance test . Outcomes included GS and SPPB . Leg power and leg strength were measured using computerized pneumatic strength training equipment and recorded in Watts and Newtons , respectively . RESULTS Participants were 68 % female , had a mean age of 75.2 , a mean of 5.5 chronic conditions , and a baseline mean SPPB score of 8.7 . After controlling for age , site , group assignment , and baseline outcome values , leg power was the only attribute in which changes were significantly associated with a large CMD in SPPB ( odds ratio (OR)=1.48 , 95 % confidence interval (CI)=1.09 - 2.02 ) and GS ( OR=1.31 , 95 % CI=1.01 - 1.70 ) . CONCLUSION Improvements in leg power , independent of strength , appear to make an important contribution to clinical ly meaningful improvements in SPPB and GS", "BACKGROUND Lower muscle mass has been correlated with poor physical function ; however , no studies have examined this relationship prospect ively . This study aims to investigate whether low muscle mass , low muscle strength , and greater fat infiltration into the muscle predict incident mobility limitation . METHODS Our study cohort included 3075 well-functioning black and white men and women aged 70 - 79 years participating in the Health , Aging , and Body Composition study . Participants were followed for 2.5 years . Muscle cross-sectional area and muscle tissue attenuation ( a measure of fat infiltration ) were measured by computed tomography at the mid-thigh , and knee extensor strength by using a KinCom dynamometer . Incident mobility limitation was defined as two consecutive self-reports of any difficulty walking one-quarter mile or climbing 10 steps . RESULTS Mobility limitations were developed by 22.3 % of the men and by 31.8 % of the women . Cox 's proportional hazards models , adjusting for demographic , lifestyle , and health factors , showed a hazard ratio of 1.90 [ 95 % confidence interval ( CI ) , 1.27 - 2.84 ] in men and 1.68 ( 95 % CI , 1.23 - 2.31 ) in women for the lowest compared to the highest quartile of muscle area ( p muscle strength were 2.02 ( 95 % CI , 1.39 - 2.94 ) and 1.91 ( 95 % CI , 1.41 - 2.58 ) , p muscle attenuation were 1.91 ( 95 % CI , 1.31 - 2.83 ) and 1.68 ( 95 % CI , 1.20 - 2.35 ) , p muscle attenuation and muscle strength independently predicted mobility limitation ( p blacks and whites . CONCLUSION Lower muscle mass ( smaller cross-sectional thigh muscle area ) , greater fat infiltration into the muscle , and lower knee extensor muscle strength are associated with increased risk of mobility loss in older men and women . The association between low muscle mass and functional decline seems to be a function of underlying muscle strength", "BACKGROUND This study was design ed to evaluate the benefits of InVEST ( Increased Velocity Specific to Task ) training on limb power and mobility among mobility-limited older adults . METHODS We conducted a single blinded , r and omized controlled trial among 138 mobility-limited community-dwelling older adults , evaluating two 16-week supervised exercise programs . The intervention group participated in InVEST training , and the control group participated in the National Institute on Aging 's ( NIA ) strength training program . Primary outcomes were changes in limb power per kilogram and mobility performance as measured by the Short Physical Performance Battery ( SPPB ) . RESULTS After 16 weeks , InVEST produced significantly greater improvements in limb power than NIA ( p=.02 ) . There was no significant difference in strength improvements . Both groups had significant changes in SPPB of greater than 1 unit . Self-reported function was also significantly improved in both groups . Differences between groups were not statistically different . In a post hoc analysis when participants were categorized by the manifestation of baseline leg velocity impairments ( N=68 ) , InVEST training produced effect size differences in SPPB that were clinical ly meaningful ( SPPB Group x Time difference 0.73 units , p=.05 ) . CONCLUSIONS Among mobility-limited older adults , both NIA and InVEST produce robust changes in observed physical performance and self-reported function . These improvements were not meaningfully different by statistical or clinical criteria . Compared with NIA , InVEST training produced greater improvements in limb power and equivalent improvements in strength . Observed differences between NIA and InVEST based upon baseline leg impairment status are informative for futures studies", "Hanson , ED , Srivatsan , SR , Agrawal , S , Menon , KS , Delmonico , MJ , Wang , MQ , and Hurley , BF . Effects of strength training on physical function : influence of power , strength , and body composition . J Strength Cond Res 23(9 ) : 2627 - 2637 , 2009-The purpose of this study was to determine ( a ) the effects of strength training ( ST ) on physical function and ( b ) the influence of strength , power , muscle volume ( MV ) , and body composition on physical function . Healthy , inactive adults ( n = 50 ) aged 65 years and older underwent strength , power , total body composition ( % fat and fat free mass [ FFM ] ) , and physical function testing before and after 22 weeks of ST . Physical function testing consisted of tasks design ed to mimic common physical activities of daily living ( ADL ) . To improve internal validity of the assessment of mid-thigh intermuscular fat , subcutaneous fat , and knee extensors MV , a 10-week unilateral ST program using the untrained leg as an internal control preceded 12 weeks of whole-body ST . Strength , power , and FFM increased significantly with ST ( all p rapid walk , 5 chair st and s , and get up and go time decreased significantly with ST in the overall group ( all p Women improved significantly in both walking test times ( both p stair climb test , whereas men improved in the stair climb test ( p walking test times . Multiple regression analysis revealed the highest R2 ( 0.28 ) for the change in chair st and s time , followed by stair climb and usual walk at 0.27 and 0.21 , respectively . ST improves performance in functional tasks important for ADLs . Changes in strength , power , and FFM are predictors of ST-induced improvements in these tasks", "OBJECTIVE To determine whether trunk extension endurance changes with training are associated with clinical ly meaningful improvements in balance among mobility-limited older adults . DESIGN Longitudinal data from a r and omized controlled trial . SETTING Outpatient rehabilitation research center . PARTICIPANTS Community-dwelling older adults ( N=64 ; mean age , 75.9y ) with mobility limitations as defined by a score of 4 to 10 on the Short Physical Performance Battery . INTERVENTIONS Sixteen weeks of progressive resistance training . MAIN OUTCOME MEASURES Outcomes were the Berg Balance Scale ( BBS ) and the Unipedal Stance Time ( UST ) . Predictors included leg strength , leg power , trunk extension endurance , and the product of heart rate and blood pressure ( RPP ) at the final stage of an exercise tolerance test . We performed an analysis of data from participants who completed 16 weeks of training by using binary outcomes defined by a clinical ly meaningful change ( CMC ) from baseline to completion of the intervention ( BBS=4 units ; UST=5s ) . The association of predictor variables with balance outcomes was examined separately and together in multivariate adjusted logistic regression models . RESULTS Trunk extension endurance in seconds ( 1.04 [ 1.00 - 1.09 ] ) was independently associated with CMC on the BBS . Trunk extension endurance ( 1.02 [ 1.00 - 1.03 ] ) was independently associated with CMC on the UST . Other physical attributes were not associated with meaningful change in balance . CONCLUSIONS Improvements in trunk extension endurance were independently associated with CMCs in balance in older adults . Leg strength , leg power , and RPP were not associated with CMC in balance . Poor trunk extension endurance may be a rehabilitative impairment worthy of further study as a modifiable factor linked to balance among older adults", "BACKGROUND Progressive loss of muscle and strength with age is often coincident with increases in adiposity , leading to a condition called sarcopenic obesity . Studies have shown sarcopenic obese adults to be at higher risk for declines in physical function . Despite this rising public health concern , no intervention studies currently exist in this population . METHODS A total of 21 sarcopenic obese adults , 60 years or older , were r and omized into two groups , strength/hypertrophy ( SH , n=9 ) and high-speed circuit ( HSC , n=8 ) and were trained for 15 weeks . The primary outcome was the SPPB modified as a measure of physical function , assessed by assessors blinded to r and omization . Secondary outcomes were lower body and upper body power and strength , instrumental activities of daily living ( IADL ) , ratings of perceived exertion ( RPE ) , body fat % ( BF% ) , skeletal muscle index ( SMI ) , and grip strength ( GRP ) . RESULTS For the SPPB results favored HSC over SH ( 1.1 , 95 % CI ( -.1 to 2.4 ) , p=.08 ) and showed a moderate effect size ( Hedge g=0.6 , 95 % CI ( -0.4 , 1.6 ) ) . For secondary outcomes , lower body power ( mean difference=158 W , 95 % CI ( 2 , 315 ) ; p=.01 ) and RPE ( mean difference=-1.5 , 95 % CI ( -2.9 , -0.12 ) ; p=.04 ) also favored HSC . IADL , SMI , BF% , upper and lower body strength and upper body power , showed no statistically significant differences between groups . CONCLUSIONS Considering the moderate effect size , the large treatment effect shown by the upper limit of the 95 % CI , the low perceived exertion , and no adverse effects , HSC training should be further investigated with a larger sample size in sarcopenic obese adults", "OBJECTIVES To evaluate weighted stair climbing exercise ( SCE ) as a means of increasing lower extremity muscle power in mobility-limited older people . DESIGN Single-blinded , r and omized controlled pilot study . SETTING Human physiology laboratory of a metropolitan university . PARTICIPANTS Forty-five community-dwelling people aged 65 and older who had baseline mobility limitations manifested by scores of 11 or lower on the Short Physical Performance Battery ( SPPB ) . INTERVENTIONS Subjects were r and omized into one of two 12-week exercise programs . The intervention group ( SCE ) ( n = 23 ) ascended and descended stairs , at a set pace , while wearing a weighted vest . The control group ( WALK ) ( n = 22 ) participated in a st and ardized walking program . MEASUREMENTS Primary and secondary outcomes included measures of muscle power and strength , submaximal aerobic capacity , and physical performance . RESULTS SCE produced 17 % improvement in double leg press peak power in comparison with WALK ( P = .013 ) and significant improvement in stair climbing power from baseline ( 12 % ) . Improvement in submaximal aerobic performance was equivalent for both groups . Although not statistically significant , effect size estimates suggest that SCE can potentially influence knee extension power and strength . Stair climb time was improved in both groups , whereas SCE produced significant improvements from baseline SPPB score in a subcohort of participants . CONCLUSIONS These findings suggest that SCE maybe a useful component of a home exercise program design ed to enhance lower extremity muscle power , aerobic capacity , and functional performance . Further investigation is needed involving larger sample sizes and direct comparisons with other forms of resistance training", "It is unclear whether strength training ( ST ) or power training ( PT ) is the more effective intervention at improving muscle strength and power and physical function in older adults . The authors compared the effects of lower extremity PT with those of ST on muscle strength and power in 45 older adults ( 74.8 + /- 5.7 yr ) with self-reported difficulty in common daily activities . Participants were r and omized to 1 of 3 treatment groups : PT , ST , or wait-list control . PT and ST trained 3 times/wk for 12 wk using knee-extension ( KE ) and leg-press ( LP ) machines at approximately 70 % of 1-repetition maximum ( 1RM ) . For PT , the concentric phase of the KE and LP was completed \" as fast as possible , \" whereas for ST the concentric phase was 2 - 3 s. Both PT and ST paused briefly at the midpoint of the movement and completed the eccentric phase of the movement in 2 - 3 s. PT and ST groups showed significant improvements in KE and LP 1RM compared with the control group . Maximum KE and LP power increased approximately twofold in PT compared with ST . At 12 wk , compared with control , maximum KE and LP power were significantly increased for the PT group but not for the ST group . In older adults with compromised function , PT leads to similar increases in strength and larger increases in power than ST", "BACKGROUND Whey protein supplementation may augment resistance exercise-induced increases in muscle strength and mass . Further studies are required to determine whether this effect extends to mobility-limited older adults . The objectives of the study were to compare the effects of whey protein concentrate ( WPC ) supplementation to an isocaloric control on changes in whole-body lean mass , mid-thigh muscle cross-sectional area , muscle strength , and stair-climbing performance in older mobility-limited adults in response to 6 months of resistance training ( RT ) . METHODS Eighty mobility-limited adults aged 70 - 85 years were r and omized to receive WPC ( 40g/day ) or an isocaloric control for 6 months . All participants also completed a progressive high-intensity RT intervention . Sample sizes were calculated based on the primary outcome of change in whole-body lean mass to give 80 % power for a 0.05-level , two-sided test . RESULTS Lean mass increased 1.3 % and 0.6 % in the WPC and control groups , respectively . Muscle cross-sectional area was increased 4.6 % and 2.9 % in the WPC and control groups , respectively , and muscle strength increased 16%-50 % in WPC and control groups . Stair-climbing performance also improved in both groups . However , there were no statistically significant differences in the change in any of these variables between groups . CONCLUSIONS These data suggest that WPC supplementation at this dose does not offer additional benefit to the effects of RT in mobility-limited older adults", "BACKGROUND Muscle power is a key predictor of physical function in older adults ; however , clinical ly meaningful improvements in leg-extensor muscle power have yet to be identified . The purpose of this study is to establish the minimal clinical ly important improvement ( MCII ) and substantial improvement ( SI ) for leg-extensor power and muscle contraction velocity in mobility-limited older adults . METHODS Data were extracted from three r and omized trials of leg-extensor muscle power training interventions ( 3- to 6-month duration ) . Measurements of leg-extensor power and velocity were obtained using dynamic bilateral leg press at 40 % and 70 % of the one-repetition maximum . Anchor-based MCIIs were calculated using selected items extracted from the Late Life Function and Disability Instrument . St and ard error of measurement and effect size methods were used to calculate the distribution-based MCII . RESULTS Data from 164 participants ( mean age : 76.6 ± 5.6 years ; Short Physical Performance Battery score : 7.8 ± 1.3 ) were used in this analysis . The respective MCII and SI estimates for 40 % leg-extensor power were 18.3 ( 9 % ) and 30.5 ( 15 % ) W , and 23.1 ( 10 % ) and 41.6 ( 18 % ) W for 70 % leg-extensor power . The respective MCII and SI estimates for 40 % average velocity were 0.03(7 % ) and 0.08(18 % ) m/s , and 0.02(6 % ) and 0.05(15 % ) m/s for 70 % average velocity . CONCLUSIONS This is the first study to establish a clinical ly meaningful improvement of leg-extensor power ( 9%-10 % ) and velocity ( 6%-7 % ) in mobility-limited older adults . These findings should be used to aid in the design and interpretation of clinical trials and interventions that target improvements in muscle power in this high-risk population", "BACKGROUND Age-related decline in muscle power may be an early indicator of balance deficits and fall risk , even in nonfrail adults . This study examined the dose-dependent effect of power training on balance performance in healthy older adults . METHODS One hundred twelve community-dwelling healthy older adults ( 69 + /- 6 years ) were r and omized to 8 - 12 weeks of power training at 20 % ( LOW ) , 50 % ( MED ) , or 80 % ( HIGH ) of maximal strength , or a nontraining control ( CON ) group . Participants trained twice weekly ( five exercises ; three sets of eight rapid concentric/slow eccentric repetitions ) using pneumatic resistance machines . Balance , muscle performance ( strength , power , endurance , contraction velocity ) , and body composition were measured . RESULTS Power training significantly improved balance performance ( p = .006 ) in participants who underwent power training compared to controls . Low intensity power training produced the greatest improvement in balance performance ( p = .048 ) . Average contraction velocity at low load ( 40 % one repetition maximum [ 1RM ] ) at baseline independently predicted improvement in balance following training ( r = -.29 , p = .004 ) . CONCLUSIONS Power training improves balance , particularly using a low load , high velocity regimen , in older adults with initial lower muscle power and slower contraction . Further studies are warranted to define the mechanisms underlying this adaptation , as well as the optimum power training intensity for a range of physiological and clinical outcomes in older adults with varying levels of health status and functional independence", "This study investigated the effect of a 10-week power training ( PT ) program versus traditional resistance training ( TRT ) on functional performance , and muscular power and strength in older men . Twenty inactive volunteers ( 60–76 years old ) were r and omly assigned to a PT group ( three 8–10 repetition sets performed as fast a possible at 60 % of 1-RM ) or a TRT group ( three 8–10 repetition sets with 2–3 s contractions at 60 % of 1-RM ) . Both groups exercised 2 days/week with the same work output . Outcomes were measured with the Rikli and Jones functional fitness test and a bench and leg press test of maximal power and strength ( 1-RM ) . Significant differences between and within groups were analyzed using a two-way analysis of variance ( ANOVA ) . At 10 weeks there was a significantly ( P measures of functional performance in the PT group . Arm curling improved by 50 versus 3 % and a 30 s chair-st and improved by 43 versus 6 % in the PT and TRT groups , respectively . There was also a significantly greater improvement in muscular power ( P The bench press improved by 37 versus 13 % , and the leg press by 31 and 8 % in the PT and TRT groups , respectively . There was no significant difference between groups in improved muscular strength . It appears that in older men there may be a significantly greater improvement in functional performance and muscular power with PT versus low velocity resistance training", "Abstract Sayers , SP and Gibson , K. High-speed power training in older adults : A shift of the external resistance at which peak power is produced . J Strength Cond Res 28(3 ) : 616–621 , 2014— Studies have shown that power training increases peak power ( PP ) in older adults . Evaluating the external resistance ( % 1 repetition maximum [ 1RM ] ) at which PP is developed is critical given that changes in the components of PP ( force and velocity ) are dependent on the % 1RM at which PP occurs . The purpose of this study was to compare the changes in PP ( and the external resistance at which PP occurred ) after 12 weeks of high-speed power training ( HSPT ) vs. traditional slow-speed strength training ( SSST ) . Seventy-two older men and women were r and omized to HSPT at 40 % of the 1RM ( HSPT : n = 24 [ 70.8 ± 6.8 years ] ) ; traditional resistance training at 80 % 1RM ( SSST : n = 22 [ 68.6 ± 7.8 years ] ) ; or control ( CON : n = 18 [ 71.5 ± 6.1 years ] ) . Measures of muscle performance were obtained at baseline and after the 12-week training intervention . Changes in muscle power and 1RM strength improved similarly with both HSPT and SSST , but HSPT shifted the external resistance at which PP was produced to a lower external resistance ( from 67 % 1RM to 52 % 1RM ) compared with SSST ( from 65 % 1RM to 62 % 1RM ) ( p ⩽ 0.05 ) , thus increasing the velocity component of PP ( change : HSPT = 0.18 ± 0.21 m·s−1 ; SSST = −0.03 ± 0.15 m·s−1 ) ( p ⩽ 0.05 ) . Because sufficient speed of the lower limb is necessary for functional tasks related to safety ( crossing a busy intersection , fall prevention ) , HSPT should be implemented in older adults to improve power at lower external resistances , thus increasing the velocity component of power and making older adults safer in their environment . These data provide clinicians with the necessary information to tailor exercise programs to the individual needs of the older adult , affecting the components of power", "OBJECTIVES To assess the ability of gait speed alone and a three-item lower extremity performance battery to predict 12-month rates of hospitalization , decline in health , and decline in function in primary care setting s serving older adults . DESIGN Prospect i ve cohort study . SETTING Primary care programs of a Medicare health maintenance organization ( HMO ) and Veterans Affairs ( VA ) system . PARTICIPANTS Four hundred eighty-seven persons aged 65 and older . MEASUREMENTS Lower extremity performance Established Population for Epidemiologic Studies of the Elderly ( EPESE ) battery including gait speed , chair st and s , and t and em balance tests ; demographics ; health care use ; health status ; functional status ; probability of repeated admission scale ( Pra ) ; and primary physician 's hospitalization risk estimate . RESULTS Veterans had poorer health and higher use than HMO members . Gait speed alone and the EPESE battery predicted hospitalization ; 41 % ( 21/51 ) of slow walkers ( gait speed hospitalized at least once , compared with 26 % ( 70/266 ) of intermediate walkers ( 0.6 - 1.0 m/s ) and 11 % ( 15/136 ) of fast walkers ( > 1.0 m/s ) ( P decline in function and health status in both health systems . Performance measures , alone or in combination with self-report measures , were more able to predict outcomes than self-report alone . CONCLUSION Gait speed and a physical performance battery are brief , quantitative estimates of future risk for hospitalization and decline in health and function in clinical population s of older adults . Physical performance measures might serve as easily accessible \" vital signs \" to screen older adults in clinical setting ", "Sayers SP , Bean J , Cuoco A , LeBrasseur NK , Jette A , Fielding RA : Changes in function and disability after resistance training : Does velocity matter ? A pilot study . Am J Phys Med Rehabil 2003;82:605–613 . Objective To compare the effects of high- and low-velocity resistance training on functional performance and disability outcomes in physically limited older women . Design A total of 16 wk of high-velocity resistance training or traditional low-velocity resistance training consisting of knee extension and leg press exercises was performed three times per week by 30 women with self-reported disability to compare their effect on functional performance and disability . Tests of dynamic balance , stair-climb time , chair-rise time , and gait velocity were used to assess changes in functional performance . Changes in disability were assessed using the Medical Outcomes Study Short Form . Results Dynamic balance and stair-climb time improved 8 % and 10 % , respectively , with training . Self-reported disability , physical functioning , role physical , and mental health improved 11 , 9 , and 5 % with training , respectively . There were no significant differences between high- and low-velocity training groups . Conclusions High- and low-velocity training achieved similar improvements in functional performance and disability . Improvements in functional performance and disability were modest compared with robust increases in strength and power . Specific modes of training or behavioral strategies may be necessary to optimize improvements in these outcomes", "OBJECTIVES Peak power declines more precipitously than strength with advancing age and is a reliable measure of impairment and a strong predictor of functional performance . We tested the hypothesis that a high-velocity resistance-training program ( HI ) would increase muscle power more than a traditional low-velocity resistance-training program ( LO ) . DESIGN R and omized controlled trial . SETTING University-based human physiology laboratory . PARTICIPANTS Thirty women with self-reported dis-ability ( aged 73 + 1 , body mass index 30.1 + 1.1 kg/mn ) . INTERVENTION We conducted a r and omized trial comparing changes in skeletal muscle power and strength after 16 weeks of HI or LO . Training was performed three times per week , and subjects completed three sets ( 8 - 10 repetitions ) of leg press ( LP ) and knee extension ( KE ) exercises at 70 % of the one-repetition maximum ( IRM ) . MEASUREMENTS One-repetition maximum ( 1 RM ) and peak power for KE and LP . RESULTS LP and KE relative training force and total work were similar between groups ( P > .05 ) . However , HI generated significantly higher power during training sessions than LO for LP ( 3.7-fold greater , P LP and KE 1RM muscle strength increased similarly in both groups asa result of the training ( P LP peak power increased significantly more in HI than in LO ( 267 W vs 139 W , P improvement in LP power at 40 % , 50 % , 60%,70 % , 80 % , and 90 % of the 1 RM than did LO ( P 1RM strength similarly and was more effective in improving peak power than was traditional LO in older women . Improvements in lower extremity peak power may exert a greater influence on age-associated reductions in physical functioning than other exercise interventions", "To examine the effects of different rest intervals on the repeatability of 1 repetition maximum ( 1RM ) efforts in the free-weight back squat exercise , 17 weight-trained men served as subjects ( mean age 22.0 years ) . One repetition maximum was tested on each of the first 2 days of testing to establish a stable baseline ( 1RM = 184.9 kg ) . Each of the next 3 sessions involved performing 2 1RM back squats , with the rest interval between attempted lifts being either 1 , 3 , or 5 minutes , assigned in a counterbalanced fashion . For the 1-minute rest interval , 13 of 17 subjects successfully completed the second lift ; for the 3-minute rest interval , 16 of 17 were successful ; and for the 5-minute rest interval , 15 of 17 were successful . Cochran Q analysis determined no significant difference ( p > 0.05 ) in the ability to repeat a successful maximal-effort back squat when different rest intervals were used . These findings are consistent with the literature for the bench-press exercise and indicate that 1-minute rest intervals are sufficient for recovery between attempted lifts during 1RM testing or training for the free-weight back squat when involving lifters of this caliber", "OBJECTIVE We examined if the predominant source of dietary protein influenced the lipoprotein-lipid profile in older men who performed resistive exercise training ( RT ) . DESIGN This is a 14-week , r and omized , repeated- measures study with a 12-week period of RT with supplementation of different sources of dietary protein ( beef and soy ) . SETTING Nutrition , Metabolism , and Exercise Laboratory , Central Arkansas Veteran 's Healthcare System , North Little Rock , Ark. Subjects Twenty-six healthy men were recruited , and 21 men ( age 65 + /- 5 years , body mass index 28.2 + /- 2.6 kg/m 2 ) completed the study . Interventions For 14 weeks , all men were counseled to self-select a lacto-ovo-vegetarian diet . For 2 weeks ( baseline ) , all men also consumed 0.6 g-protein/kg per day from portioned quantities of soy-based texturized vegetable protein foods . For the next 12 weeks , 11 men were r and omized to continue with texturized vegetable protein foods ( VEG group ) , whereas 10 men were r and omized to receive 0.6 g-protein/kg per day from portioned quantities of beef ( BEEF group ) and continue their otherwise lacto-ovo-vegetarian diet . All men participated in RT 3 d/wk during this 12-week period . Assessment s of upper and lower body muscle strength and power , serum lipoprotein-lipid profile , and dietary nutrient intakes were made at baseline and week 12 of RT ( POST ) . RESULTS The BEEF and VEG groups increased ( P overall muscle strength and muscle power with RT , with no differences between groups . From baseline to POST , the BEEF group had increased concentrations of high-density lipoprotein cholesterol ( P = .025 ; HDL-C ) , low-density lipoprotein cholesterol ( P = .027 ; LDL-C ) , and total cholesterol ( P = .015 : CHOL ) , with no changes ( P > .05 ) in triacylglycerol ( TG ) , the CHOL/HDL-C ratio , or the TG/HDL-C ratio . The VEG group did not experience within-group changes ( P > .05 ) in any lipoprotein-lipid parameter . At POST , the concentrations of HDL-C , LDL-C , and CHOL were greater in the BEEF group compared with the VEG group . There were significant interaction effects for HDL-C ( P = .004 ) and the TG/HDL-C ratio ( P = .022 ) . Multiple regression analysis determined that , regardless of intervention , change in the saturated fat/fiber ratio ( SF/fiber ) predicted CHOL ( adjusted R 2 = 0.34 ) ; the SF/fiber ratio predicted LDL-C ( adjusted R 2 = 0.36 ) ; the cholesterol/fiber intake ratio predicted HDL-C ( adjusted R 2 = 0.26 ) , and the change in carbohydrate intake predicted the CHOL/HDL-C ratio ( adjusted R 2 = 0.37 ) and TG ( adjusted R 2 = 0.44 ) . CONCLUSIONS These results suggest that the lipoprotein-lipid profile in these older men was differentially affected by supplementation with beef versus soy-based foods during RT . Regardless of group , the lipoprotein-lipid changes were predicted by differences in the SF/fiber ratio and cholesterol/fiber ratio and increases in carbohydrate intake over time", "UNLABELLED Power-based resistance training ( PWT ) , using low load and high velocity , can improve physical function and quality of life in older persons . Patients with Parkinson 's disease ( PD ) , exhibiting muscular weakness and reduced movement speed , have been shown to be benefit from resistance training ; however , little is known about the advantages of PWT for PD . PURPOSE To evaluate the effects of PWT on bradykinesia and muscular performance in older patients with PD . METHODS Twenty-six patients with mild to moderate PD were r and omly assigned to a PWT or control group ( CON ) . The PWT program was three months , incorporating two sessions/wk of high-speed resistance training combined balance and agility drills . Outcome measures included : upper and lower limb bradykinesia scores , one repetition maximums ( 1RM ) and peak powers on biceps curl , chest press , leg press , hip abduction and seated calf , and quality of life ( PDQ-39 ) . RESULTS The PWT group produced significant improvement in both upper and lower limbs bradykinesia scores , 1RM and muscle peak power ( p clinical measure of bradykinesia and muscle peak power were observed after training . Significant improvements were seen in the PDQ-39 overall score , subsections for mobility , activities of daily living and social support for the PWT group . CONCLUSION The 3-month PWT program significantly reduced bradykinesia and increased muscle strength and power in older patients with PD . Power training is an effective training modality to improve physical function and quality of life for PD", "Abstract Ni , M and Signorile , JF . High-speed resistance training modifies load-velocity and load-power relationships in Parkinson 's disease . J Strength Cond Res 31(10 ) : 2866–2875 , 2017—Muscle power is a major neuromuscular factor affecting motor function and independence in patients with Parkinson 's disease ( PD ) , and it is commonly targeted using high-speed exercise . This study examined the changes in velocities ( Vpp ) and percent loads ( % 1RMpp ) at peak power and load-velocity ( L-V ) and load-power ( L-P ) relationships , result ing from resistance training because of exercise choice and loading in older patients with PD . Fourteen older adults with mild to moderate PD participated in a 12-week r and omized controlled power training trial . Changes in L-V and L-P relationships for the biceps curl , chest press , leg press , hip abduction , and seated calf were assessed using pneumatic resistance machines at loads ranging from 30 through 90 % of subjects ' 1 repetition maximum for each exercise . Significant increases in Vpp were seen for biceps curl , leg press , hip abduction , and seated calf and decreases in % 1RMpp were noted for biceps curl and hip abduction . Additionally , unique patterns of change were seen in these relationships across exercises , with biceps curl , chest press , and leg press showing the greatest shifts at the lower load end of the loading spectrum , and hip abduction and seated calf showing greatest responses at the higher end . The patterns of change in L-V and L-P relationships provide evidence for the unique responses of the specific muscle groups and joints to the exercises evaluated and offer a framework for more exacting exercise prescriptions in patients with PD" ]	41189410-06ff-11f0-808a-c43d1ab1c353
OBJECTIVE To determine the overall effect of non-diet , weight-neutral interventions on factors such as weight , biochemical measures , food and activity behavior , body image , and mental health . DESIGN Systematic review of intervention literature . SETTING Group classes in community and worksite setting s ( 14 studies ) , and individual counseling ( 1 ) and online education ( 1 ) in college setting s. PARTICIPANTS Eighteen research articles ( representing 16 studies ) evaluating non-diet interventions using quasi-experimental and r and omized study design s with either a comparison or control group . MAIN OUTCOME MEASURES Anthropometric , physiological , psychological , and dietary intake . ANALYSIS Systematic search of 168 articles and review of 18 articles meeting inclusion ary criteria . RESULTS Non-diet interventions result ed in statistically significant improvements in disordered eating patterns , self-esteem , and depression . None of the interventions result ed in significant weight gain or worsening of blood pressure , blood glucose , or cholesterol , and in 2 studies biochemical measures improved significantly compared with the control or diet group . Primary limitations were inconsistent definitions of non-diet approaches and the use of different assessment instruments for measuring outcomes . CONCLUSIONS AND IMPLICATION S Because of the long-term ineffectiveness of weight-focused interventions , the psychological improvements seen in weight-neutral , non-diet interventions warrant further investigation	[ "OBJECTIVE . To assess whether weight-related teasing predicts the development of binge eating , unhealthy weight control behaviors , and frequent dieting among male and female adolescents . METHODS . A prospect i ve study was conducted with an ethnically and socioeconomically diverse sample of 2516 adolescents who completed surveys at both time 1 ( 1998–1999 ) and time 2 ( 2003–2004 ) of the Project EAT ( Eating Among Teens ) study . RESULTS . In 1998–1999 , approximately one fourth of participants reported being teased about their weight at least a few times a year . After adjustment for age , race/ethnicity , socioeconomic status ( SES ) , and BMI , boys who were teased about their weight were more likely than their peers to initiate binge eating with loss of control and unhealthy weight control behaviors 5 years later . The predicted prevalence for incident binge eating behaviors with loss of control among boys who were teased was 4.1 % as compared with 1.4 % for those who were not teased , after adjustment for age , race/ethnicity , SES , and BMI . For unhealthy weight control behaviors at time 2 , the predicted prevalence was 27.5 % among boys who were teased and 19.3 % for boys who were not teased , after adjustment for age , race/ethnicity , SES , and BMI . Girls who were teased were more likely than their peers to become frequent dieters . The predicted prevalence for incident frequent dieting among girls who were teased was 18.2 % as compared with 11.0 % for those who were not teased , after adjustment for age , race/ethnicity , SES , and BMI . CONCLUSIONS . Weight teasing in adolescence predicts disordered eating behaviors at 5-year follow-up . The patterns of these associations differ by gender . Reducing teasing through educational interventions and policies may reduce the level of disordered eating behaviors among youths", "OBJECTIVE To assess whether dieting to control weight was associated with weight change among children and adolescents . METHODS A prospect i ve study was conducted of 8203 girls and 6769 boys who were 9 to 14 years of age in 1996 , were in an ongoing cohort study , and completed at least 2 annual question naires between 1996 and 1999 . Dieting to control weight , binge eating , and dietary intake were assessed annually from 1996 through 1998 with instruments design ed specifically for children and adolescents . The outcome measure was age- and sex-specific z score of body mass index ( BMI ) . RESULTS In 1996 , 25.0 % of the girls and 13.8 % of the boys were infrequent dieters and 4.5 % of the girls and 2.2 % of the boys were frequent dieters . Among the girls , the percentage of dieters increased over the following 2 years . Binge eating was more common among the girls , but in both sexes , it was associated with dieting to control weight ( girls : infrequent dieters , odds ratio [ OR ] : 5.10 ; frequent dieters , OR : 12.4 ; boys : infrequent dieters , OR : 3.49 ; frequent dieters , OR : 7.30 ) . During 3 years of follow-up , dieters gained more weight than nondieters . Among the girls , frequency of dieting was positively associated with increases in age- and sex-specific z scores of BMI ( beta = 0.05 and beta = 0.04 for frequent and infrequent dieters vs nondieters ) . Among the boys , both frequent and infrequent dieters gained 0.07 z scores of BMI more than nondieters . In addition , boys who engaged in binge eating gained significantly more weight than nondieters . CONCLUSIONS Although medically supervised weight control may be beneficial for overweight youths , our data suggest that for many adolescents , dieting to control weight is not only ineffective , it may actually promote weight gain", "OBJECTIVE : To evaluate a modified cognitive – behavioural treatment ( M-CBT ) for weight management which addresses both the psychosocial costs and the physiological health risks of obesity , without a focus on weight loss . DESIGN : R and omized controlled trial comparing M-CBT with st and ard cognitive – behavioural therapy (S-CBT).SUBJECTS : Sixty-three overweight women with body mass index ( BMI ) ≥28 kg/m2 , mean age=47.5 and mean BMI = 35.4 . MEASURES : Weight , waist and hip circumference , blood lipids , blood glucose , blood pressure , psychological well-being , depression , self esteem , stress , binge eating , eating style , body image , nutrient intake , aerobic fitness , activity levels , patient satisfaction with treatment . RESULTS : Both M-CBT and S-CBT achieved improvements in a broad range of physical , psychological and behavioural variables . Weight loss in the S-CBT group was greater than in the M-CBT group immediately after treatment , but both groups lost weight . Participants in the M-CBT group continued to lose weight up to the 1 y follow-up . M-CBT was evaluated positively by participants . CONCLUSIONS : Both M-CBT and S-CBT programmes were successful at inducing modest weight loss , as well as improving emotional well-being , reducing distress , increasing activity and fitness , improving dietary quality and reducing cardio-vascular disease risk factors . The improvements were maintained or continued at 1 y follow-up . These results suggest that treatment based on the new weight-control paradigm which emphasizes sustained lifestyle change without emphasis on dieting , can produce modest benefits to health and well-being ", "BACKGROUND Several studies have examined attitudes about obesity among food and nutrition professionals , yielding mixed results , and no experimental research has tested the impact of dietitians ' attitudes on their treatment practice s or health evaluations with obese patients . OBJECTIVE This study investigated attitudes of dietetics students toward obese persons and tested whether a patient 's body weight influences students ' treatment decisions and health evaluations within a r and omized experiment . DESIGN Between the months of September and December 2007 , a convenience sample of 182 dietetics undergraduate students ( 92 % women ; mean age 23.1+/-5.4 years ) from colleges throughout the United States completed online self-report surveys to assess weight bias ( using the Fat Phobia Scale ) . Participants were also r and omly assigned to read one of four mock health profiles of patients who varied only by weight-related characteristics ( eg , obese or average weight ) and sex ( male or female ) , and asked to make judgments about the patient 's health status and participation in treatment . STATISTICAL ANALYSES PERFORMED To compare group data , multiple analysis of variance was used to test for an effect of the patient 's body mass index on participants ' health evaluations and their perceptions of patients in each of the four experimental conditions . Correlations were calculated between mean fat phobia scores and perceptions of patients . RESULTS Participants in all conditions expressed a moderate amount of fat phobia ( mean=3.7 ) , and students rated obese patients as being less likely to comply with treatment recommendations compared with nonobese patients ( P obese patients ' diet quality and health status to be poorer than nonobese patients , despite equivalent nutritional and health information across weight categories for each sex in patient profiles . In contrast , obese and nonobese patients were rated to be similarly motivated , receptive , and successful in treatment . CONCLUSION Implication s of these findings for education and intervention in dietetics training are discussed , with emphasis on increasing awareness of weight bias in existing dietetics curricula", "Obese individuals tend to behave more impulsively than healthy weight individuals across a variety of measures , but it is unclear whether this pattern can be altered . The present study examined the effects of a mindful eating behavioral strategy on impulsive and risky choice patterns for hypothetical food and money . In Experiment 1 , 304 participants completed computerized delay and probability discounting tasks for food-related and monetary outcomes . High percent body fat ( PBF ) predicted more impulsive choice for food , but not small-value money , replicating previous work . In Experiment 2 , 102 r and omly selected participants from Experiment 1 were assigned to participate in a 50-min workshop on mindful eating or to watch an educational video . They then completed the discounting tasks again . Participants who completed the mindful eating session showed more self-controlled and less risk-averse discounting patterns for food compared to baseline ; those in the control condition discounted similarly to baseline rates . There were no changes in discounting for money for either group , suggesting stimulus specificity for food for the mindful eating condition", "OBJECTIVE To evaluate the effectiveness of the \" My Body Knows When \" intuitive-eating ( IE ) program tailored to assist Fort Drum military spouses in rejecting the dieting mentality . METHODS R and omized prospect i ve study ( N = 61 ) evaluating dieting mentality and health indicators for a 10-week intervention based on 10 IE principles . The program was developed through the PRECEDE/PROCEED ( PP ) health promotion planning model . RESULTS The intuitive-eating program was able to significantly transition participants away from a dieting mentality ( P intuitive-eating lifestyle behaviors . CONCLUSIONS IE is a holist approach to long-term healthy behavior change and would benefit from an extended support system to improve effectiveness", "This study explored the efficacy of a mindfulness-based intervention for problematic eating behavior . A non- clinical sample of 26 women with disordered eating behavior was r and omly assigned to an 8-week MBCT-based eating intervention or a waiting list control group . Data were collected at baseline and after 8 weeks . Compared to controls , participants in the mindfulness intervention showed significantly greater decreases in food cravings , dichotomous thinking , body image concern , emotional eating and external eating . These findings suggest that mindfulness practice can be an effective way to reduce factors that are associated with problematic eating behaviour", "OBJECTIVE To assess the effects of a \" Health-At-Every-Size \" ( HAES ) intervention on eating behaviors and appetite ratings in 144 premenopausal overweight women . RESEARCH METHODS AND PROCEDURES Women were r and omly assigned to one of the 3 groups : HAES group , social support ( SS ) group , and control group ( N = 48 in each group ) . Interventions were conducted over a 4-month period , and measurements were taken before and after this period . Eating behaviors ( cognitive dietary restraint , disinhibition , and susceptibility to hunger ) were evaluated by the Three-Factor Eating Question naire . Appetite ratings ( desire to eat , hunger , fullness , and prospect i ve food consumption ) were assessed by visual analogue scales before and after a st and ardized breakfast . RESULTS More important decreases in susceptibility to hunger and external hunger were observed in the HAES group when compared with the SS group ( p=0.05 , for susceptibility to hunger ) and the control group ( p=0.02 and p=0.005 , for susceptibility to hunger and external hunger , respectively ) . In addition , women from the HAES group had more important decreases in postpr and ial area under the curve for desire to eat ( p=0.02 ) and hunger ( p=0.04 ) when compared with the control group . The change in the desire to eat noted in the HAES group was also different from the one observed in SS group ( p=0.02 ) . Women from the HAES group experienced significant weight loss at 4 months ( -1.6+/-2.5 kg , p flexible restraint was significantly related to a greater weight loss in both HAES and SS groups ( r=-0.39 , p habitual susceptibility to disinhibition was also associated with a greater weight loss in HAES and control groups ( r=0.31 , p HAES intervention could have significant effects on eating behaviors and appetite ratings in premenopausal overweight women , when compared with an SS intervention or a control group", "OBJECTIVE : To document attitudes and current practice s of Australian dietitians in the management of overweight and obesity , and to examine their training needs . DESIGN : Cross-sectional postal survey of a r and omly selected sample of members of the Dietitians Association of Australia . SUBJECTS : 400 dietitians ( 66 % of those surveyed ) . MEASURES : Question naire-based measures of dietitian 's views of obesity , education and training in weight management , definitions and perceptions of success , professional preparedness , approaches to weight management , strategies recommended for weight management , and problems and frustrations experienced . RESULTS : Dietitians viewed themselves as potential leaders in the field of weight management , and saw this area as an important part of their role . While they considered themselves to be the best-trained professionals in this area , many felt that their training was poor and many were pessimistic about intervention outcomes . Despite this , most dietitians held views that were current , and regularly employed many of the elements of known best practice in management . However , important areas of weakness included : providing opportunities for long-term follow-up ; providing a range of management interventions ; promoting self-monitoring of diet and exercise ; and promoting opportunities for social support . CONCLUSIONS : This study suggests that training in and advocacy for the management and prevention of overweight and obesity are priority areas for dietitians , and that formal studies to evaluate dietitians ’ effectiveness in management should be undertaken", "A r and omized trial was conducted to see if there could be effective alternatives to dieting for obese women . It compared a 12-week ( I h/week ) education intervention , a 12-week ( 2 h/week ) psychoeducational intervention , and a control group on self-esteem , body dissatisfaction , and restrained eating of obese women . Secondary variables of interest were social adjustment , symptoms of depression , scores on bulimia , and drive for thinness , weight , and blood pressure . Complete data were available at pre- and posttest time for 78 women . A MANCOVA indicated that the psychoeducation group improved over the control group on self-esteem , restraint , and body dissatisfaction . The education group did not differ statistically from the control group at posttest . Means of weight and blood pressure did not change . A nondieting approach can be beneficial to the emotional health of obese women without changing weight and blood pressure risk factors for other morbidity", "OBJECTIVE Examine a model that encourages health at every size as opposed to weight loss . The health at every size concept supports homeostatic regulation and eating intuitively ( ie , in response to internal cues of hunger , satiety , and appetite ) . DESIGN Six-month , r and omized clinical trial ; 2-year follow-up . SUBJECTS White , obese , female chronic dieters , aged 30 to 45 years ( N=78 ) . SETTING Free-living , general community . INTERVENTIONS Six months of weekly group intervention ( health at every size program or diet program ) , followed by 6 months of monthly aftercare group support . MAIN OUTCOME MEASURES Anthropometry ( weight , body mass index ) , metabolic fitness ( blood pressure , blood lipids ) , energy expenditure , eating behavior ( restraint , eating disorder pathology ) , and psychology ( self-esteem , depression , body image ) . Attrition , attendance , and participant evaluations of treatment helpfulness were also monitored . STATISTICAL ANALYSIS PERFORMED Analysis of variance . RESULTS Cognitive restraint decreased in the health at every size group and increased in the diet group , indicating that both groups implemented their programs . Attrition ( 6 months ) was high in the diet group ( 41 % ) , compared with 8 % in the health at every size group . Fifty percent of both groups returned for 2-year evaluation . Health at every size group members maintained weight , improved in all outcome variables , and sustained improvements . Diet group participants lost weight and showed initial improvement in many variables at 1 year ; weight was regained and little improvement was sustained . CONCLUSIONS The health at every size approach enabled participants to maintain long-term behavior change ; the diet approach did not . Encouraging size acceptance , reduction in dieting behavior , and heightened awareness and response to body signals result ed in improved health risk indicators for obese women", "This study examined the prospect i ve relations of naturalistic weight-reduction efforts to growth in relative weight and onset of obesity with data from a community study of female adolescents ( N = 692 ) . Initial self-labeled dieting , appetite suppressant/laxative use , incidental exercise , vomiting for weight-control purpose s , and binge eating predicted elevated growth in relative weight over the 4-year period . Dietary restraint , self-labeled dieting , exercise for weight-control purpose s , and appetite suppressant/laxative use predicted an increased risk for obesity onset . Data imply that the weight-reduction efforts reported by adolescents are more likely to result in weight gain than in weight loss and suggest the need to educate youth on more effective weight-control strategies", "Purpose . To identify impact of an online nutrition and physical activity program for college students . Design . R and omized , controlled trial using online question naires and on-site physical and fitness assessment s with measurement intervals of 0 ( baseline ) , 3 ( postintervention ) , and 15 months ( follow-up ) . Setting . Online intervention delivered to college students ; a central ized Web site was used for recruitment , data collection , data management , and intervention delivery . Subjects . College students ( 18–24 years old , n = 1689 ) , from eight universities ( Michigan State University , South Dakota State University , Syracuse University , The Pennsylvania State University , Tuskegee University , University of Rhode Isl and , University of Maine , and University of Wisconsin ) . Intervention . A 10-lesson curriculum focusing on healthful eating and physical activity , stressing nondieting principles such as size acceptance and eating competence ( software developer : Rainstorm , Inc , Orono , Maine ) . Measures . Measurements included anthropometrics , cardiorespiratory fitness , fruit/vegetable ( FV ) intake , eating competence , physical activity , and psychosocial stress . Analysis . Repeated measures analysis of variance for outcome variables . Results . Most subjects were white , undergraduate females ( 63 % ) , with 25 % either overweight or obese . Treatment group completion rate for the curriculum was 84 % . Over 15 months , the treatment group had significantly higher FV intake ( + .5 cups/d ) and physical activity participation ( + 270 metabolic equivalent minutes per week ) than controls . For both groups , anthropometric values and stress increased , and fitness levels decreased . Gender differences were present for most variables . First-year males and females gained more weight than participants in other school years . Conclusion . A 10-week online nutrition and physical activity intervention to encourage competence in making healthful food and eating decisions had a positive , lasting effect on FV intake and maintained baseline levels of physical activity in a population that otherwise experiences significant declines in these healthful behaviors", "BACKGROUND Poor long-term success observed with current weight-control strategies stresses the relevance to explore new weight management approaches . OBJECTIVE To assess the effects of a Health-At-Every-Size ( HAES ) intervention on eating behaviors , appetite sensations , metabolic and anthropometric variables , and physical activity levels in women at 6-month and 1-year postintervention . DESIGN R and omized controlled trial ; measurements at baseline , at the end of the intervention period ( 4 months ) , and at 6-month and 1-year postintervention ( 10 months and 16 months , respectively ) . Intervention and testing took place from September 2003 to August 2006 . PARTICIPANTS / SETTING Premenopausal overweight/obese women ( n=144 ; mean age of 42.3+/-5.6 years ) , recruited from free-living , general community . INTERVENTION Women were r and omly assigned to : HAES group ( n=48 ) , social support group ( n=48 ) , or control group ( n=48 ) . MAIN OUTCOME MEASURES Eating behaviors ( restraint , disinhibition , and susceptibility to hunger ) , appetite ratings ( desire to eat , hunger , fullness , and prospect i ve food consumption ) , anthropometric and metabolic variables ( body mass index , waist and hip circumferences , blood lipid levels , and blood pressure ) , and engagement in moderate to intense physical activity ( energy cost > or = 1.2 k cal x kg(-1 ) x 15 minutes(-1 ) [ > or = 4.8 metabolic equivalents ] ) . STATISTICAL ANALYSES PERFORMED Changes for each dependent variable were assessed by linear mixed models according to a group ( HAES vs social support vs control ) by time ( baseline vs 4 months vs 10 months vs 16 months ) split-plot design . RESULTS Situational susceptibility to disinhibition and susceptibility to hunger significantly decreased over time in both HAES group ( -0.9+/-0.2 and -1.3+/-0.5 , respectively ) and the social support group ( -0.4+/- 0.2 and -1.4+/-0.5 , respectively ) . Although eating behavior scores observed at 16 months did not differ between HAES and social support groups ( situational susceptibility to disinhibition : 2.5+/-0.2 in HAES group vs 2.7 + /- 0.2 in social support group ; susceptibility to hunger : 4.2+/-0.5 in both groups ) , they were lower in these groups than scores noted in the control group ( 3.3+/-0.2 for situational susceptibility to disinhibition and 5.9+/-0.5 for susceptibility to hunger ) . CONCLUSIONS These results suggest that , when compared to a control group , an HAES approach could have long-term beneficial effects on eating behaviors related to disinhibition and hunger . In addition , our study did not show distinctive effects of the HAES approach in comparison to a social support intervention", "This study evaluated the effectiveness of nondieting versus dieting treatments for overweight , binge-eating women . Participants ( N = 219 ) were r and omly assigned to 1 of 3 groups : diet treatment ( DT ) , nondiet treatment ( NDT ) , or wait-list control ( WLC ) . DT received a balanced-deficit diet reinforced with behavioral strategies . NDT received therapy design ed to help participants break out of their dieting cycles . Treatment in both conditions was administered in weekly groups for 6 months , followed by 26 biweekly maintenance meetings , for a total of 18 months of contact . At 6 months posttreatment , DT lost 0.6 kg while NDT gained 1.3 kg . Both treatment groups reduced their Binge Eating Scale scores significantly more than WLC . At 18-month follow-up , both treatment groups experienced weight gain but maintained similar reductions in binge eating . Results indicate that neither intervention was successful in producing short- or long-term weight loss . Therapist biases , which may have affected treatment integrity , and other method ological issues are discussed in relation to the small weight losses achieved", "Mindful eating offers promise as an effective approach for weight management and glycemic control in people with diabetes . Diabetes self-management education ( DSME ) is an essential component of effective self-care . Yet , little research has compared the effect of mindful eating to DSME-based treatment . This study compared the impact of these two interventions in adults with type 2 diabetes mellitus . A prospect i ve r and omized controlled trial with two parallel interventions was used . Participants included adults age 35 to 65 years with type 2 diabetes mellitus for 1 year or more , body mass index ( BMI ) of 27 or more , and hemoglobin A1c ( HbA1c ) of 7 % or more who were r and omly assigned to a 3-month mindful eating ( MB-EAT-D ; n=27 ) or Smart Choices ( SC ) DSME-based ( n=25 ) intervention . Follow-up occurred 3 months after intervention completion . Dietary intake , physical activity , weight , HbA1c and fasting plasma glucose , and fasting insulin were assessed using repeated measures analysis of variance with contrast analysis . There was no significant difference between groups in the change in weight or glycemia at study end . Significant difference occurred between groups in the change in dietary intake/1,000 kcal of trans fats , total fiber , and sugars ( all P reduction in weight ( -2.92 ± 0.54 kg for SC vs -1.53 ± 0.54 kg for MB-EAT-D ) and HbA1c ( -0.67 ± 0.24 % for SC and -0.83 ± 0.24 % for MB-EAT-D ) were significant ( P load occurred ( all P groups . Training in mindful eating and diabetes self-management facilitate improvement in dietary intake , modest weight loss , and glycemic control . The availability of effective treatments gives patients with diabetes choices in meeting their self-care needs", "OBJECTIVE To compare three non-dieting interventions that focused on lifestyle change rather than weight loss , in terms of the sustainability of improvements in lifestyle behaviors , psychological well-being and medical symptoms at 2 years . METHOD In Dunedin , New Zeal and in 2002/2003 , 225 obese/overweight women ( BMI > or = 28 ; 25 - 68 years ) participated in a r and omised , intention-to-treat trial comparing two group programs ( P1 , P2 ) and a self-guided mail-delivered program ( P3 ) . Only P1 included intensive relaxation response training . All three non-dieting interventions involved a 10-week program , followed by an eight-month support phase . Participants completed baseline , 1-year and 2-year assessment s. Outcomes included behavioral , psychological and medical symptom measures and a composite success score . RESULTS 118 participants completed the 2-year follow-up . Only among P1 participants were the reductions in psychological distress and medical symptoms achieved at 1 year , also maintained at 2 years . At 2 years , P1 participants had significantly greater increases in stress management behaviors than those in P2 ( p success scores than those in P3 ( p mean weight was unchanged at 2 years . CONCLUSION Inclusion of relaxation response training in a healthy lifestyle program facilitates long-term maintenance of psychological and medical symptom improvements even in the absence of weight loss", "OBJECTIVE Morbidly obese individuals are unlikely to reach and maintain normative weights . Thus , interventions aim ed at alleviating corollary problems , independent of attempts at weight loss , are appropriate . A cognitive group treatment program ( CT ) was developed which incorporated a nondieting approach , regular exercise , and use of alternative coping skills . Weight loss per se was not a focus of the intervention . The purpose of the current work was to evaluate this program in a controlled , comparative treatment outcome study . METHOD Sixty-two obese women with a history of treatment failures were r and omly assigned to the CT program , a behavior therapy weight loss program ( BT ) , or a wait-list control group . RESULTS For CT participants , depression , anxiety , and eating-related psychopathology decreased significantly over the course of treatment while perceptions of self-control increased ; BT and control subjects showed no significant changes in these variables . Women in both active treatment groups lost significant amounts of weight , while members of the control group showed a nonsignificant increase in weight . At 6-month follow-up , treatment benefits were maintained . DISCUSSION Findings suggest that interventions not directly aim ed at weight loss can enhance psychological well-being and thus may be appropriate for some obese women", "Purpose . Determine if a “ nondieting ” intervention focused on intensive training in eliciting the relaxation response enhances health outcomes compared with nondieting interventions without such training . Design . R and omized trial with follow-up at 10 weeks , 4 months , and 12 months . Setting . General community . Subjects . Total of 225 overweight and obese women with at least one other cardiovascular risk factor . Interventions . Three 10-week nondieting interventions : a group program ( P1 ) focused on intensive training in techniques for eliciting the relaxation response ( n = 60 ) , a group program ( P2 ) focused on healthy eating and physical activity ( n = 61 ) , and a self-guided , mail-delivered version of P2 ( P3 ; n = 101 ) . Measures . The Revised Symptom Checklist measured psychological distress , the Medical Symptoms Checklist measured the experience of medical symptoms , and the Health-Promoting Lifestyle Profile measured a range of lifestyle behaviors . Self-efficacy for low-fat eating , intuitive eating , and body mass index were also assessed . Analysis . An intention-to-treat analysis was used . Results . At 12 months , P1 produced statistically greater improvements in stress management behaviors and medical symptom discomfort and was the only program to significantly improve self-efficacy for low-fat eating . In P1 , the effect sizes for reductions in depression ( 0.75 ) and interpersonal sensitivity ( 0.85 ) were large . At 12 months , mean weight was unchanged . Conclusion . Inclusion of intensive relaxation response training in a nondieting program for overweight women enhanced stress management and medical symptoms outcomes but not weight outcomes" ]	4118944c-06ff-11f0-808a-c43d1ab1c353
OBJECTIVES The cholinergic-adrenergic hypothesis of mania and depression states that depression is characterized by an increase in central cholinergic activity relative to noradrenergic tone . Scopolamine is a central ly acting competitive inhibitor of the muscarinic cholinergic receptor site . This review seeks to find all available data investigating scopolamine as an antidepressant . METHODS A systematic review of all the published and unpublished or ongoing literature was conducted via Ovid MEDLINE . Keywords used for the search were " scopolamine hydrobromide " in association with one of the following : " depression , " " antidepressive agents , " " depressive disorder , " " depression , chemical , " and " affect . " PubMed was also search ed using " scopolamine " ( all fields ) and " antidepressant " ( all fields ) or " depression " ( all fields ) . RESULTS A small study with elderly patients failed to show a statistically significant improvement in depression when measured at 120 minutes after infusion . A second small , well-controlled study using intramuscular scopolamine showed a small but statistically significant improvement in depression on the morning after the second dose was received . Two double-blind r and omized placebo-controlled crossover trials with intravenous scopolamine 4.0 μg/kg infusions showed a significant improvement in depressive symptoms seen as soon as 3 days after the first treatment . Further data analyses showed a greater antidepressant effect in women , significant improvements in bipolar depression , and 85 % success rates predicting who will respond to treatment . CONCLUSIONS Scopolamine is an effective and rapid antidepressant in both unipolar and bipolar depression , working as quickly as 3 days after initial infusion . Independent replication would greatly enhance the literature	[ "Of heuristic value in underst and ing the neurochemistry of major depression is whether the hypothalamo-pituitary-adrenocortical ( HPA ) axis hyperactivity that occurs in this illness can be related to putative neurotransmitter dysfunction(s ) . Cholinergic neurotransmission stimulates hypothalamic corticotropin releasing hormone ( CRH ) and arginine vasopressin ( AVP ) secretion , both of which stimulate pituitary corticotropin ( ACTH ) secretion , but whether the HPA axis in humans is activated only by doses of cholinergic agonists that produce noxious side effects remains controversial . To test the hypothesis of increased cholinergic sensitivity in major depression , physostigmine ( PHYSO ) , a reversible cholinesterase inhibitor , was administered to patients and control subjects at a dose that elevated plasma ACTH , cortisol , and AVP concentrations but produced few or no side effects . Exogenous AVP also was administered to determine if it would augment the effect of low-dose PHYSO on the HPA axis . Twelve premenopausal or estrogen-replaced female major depressives , 12 individually matched female control subjects , eight male major depressives , and eight matched male control subjects underwent four test sessions 5 - 7 days apart : PHYSO ( 8 microg/kg IV ) , AVP ( 0.08 U/kg IM ) , PHYSO + AVP , and saline control . Serial blood sample s were taken before and after pharmacologic challenge and analyzed for ACTH1 - 39 , cortisol , and AVP . Estradiol and testosterone were also measured at each test session . PHYSO ( 8 microg/kg ) significantly increased plasma ACTH , cortisol , and AVP , while producing no side effects in approximately half the subjects and predominantly mild side effects in the other half . These hormone increases following PHYSO occurred primarily in the female depressives and the male control subjects and were not significantly related to the presence or absence of side effects . The greater the ACTH and AVP responses to PHYSO , the stronger their correlation , suggesting that AVP may have been acting as a secretagogue for ACTH . Administered AVP significantly increased the secretion of ACTH in the patients and control subjects to a similar degree , and AVP given after PHYSO did not augment the HPA axis response to a greater degree in the depressives than in the control subjects . Plasma estradiol and testosterone were within the normal range for all four groups of subjects and were not significantly related to their HPA axis hormone responses . The study results support the hypothesis of heightened cholinergic sensitivity in premenopausal female , but not in male , patients with major depression . The low dose of PHYSO used may represent a useful paradigm for central cholinergic stimulation of the HPA axis", "CONTEXT The need for improved therapeutic agents that more quickly and effectively treat depression is critical . In a pilot study we evaluated the role of the cholinergic system in cognitive symptoms of depression and unexpectedly observed rapid reductions in depression severity following the administration of the antimuscarinic drug scopolamine hydrobromide ( 4 microg/kg intravenously ) compared with placebo ( P = .002 ) . Subsequently a clinical trial was design ed to assess more specifically the antidepressant efficacy of scopolamine . OBJECTIVE To evaluate scopolamine as a potential antidepressant agent . DESIGN Two studies were conducted : a double-blind , placebo-controlled , dose-finding study followed by a double-blind , placebo-controlled , crossover clinical trial . SETTING The National Institute of Mental Health . Patients Currently depressed out patients aged 18 to 50 years meeting DSM-IV criteria for recurrent major depressive disorder or bipolar disorder . Of 39 eligible patients , 19 were r and omized and 18 completed the trial . INTERVENTIONS Multiple sessions including intravenous infusions of placebo or scopolamine hydrobromide ( 4 microg/kg ) . Individuals were r and omized to a placebo/scopolamine or scopolamine/placebo sequence ( series of 3 placebo sessions and series of 3 scopolamine sessions ) . Sessions occurred 3 to 5 days apart . MAIN OUTCOME MEASURES Psychiatric evaluations using the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale were performed to assess antidepressant and antianxiety responses to scopolamine . RESULTS The placebo/scopolamine group showed no significant change during placebo infusion vs baseline ; reductions in depression and anxiety rating scale scores ( P placebo . The scopolamine/placebo group also showed reductions in depression and anxiety rating scale scores ( P . In both groups , improvement was significant at the first evaluation after scopolamine administration ( P < or = .002 ) . CONCLUSION Rapid , robust antidepressant responses to the antimuscarinic scopolamine occurred in currently depressed patients who predominantly had poor prognoses", "Identifying predictors of antidepressant response will facilitate the successful treatment of patients suffering from depression . Scopolamine produces robust antidepressant responses in unipolar and bipolar depression . Here we evaluate the potential for baseline self-ratings to predict treatment response to scopolamine . Fifty-one unipolar and bipolar patients participated in a double-blind , placebo-controlled crossover trial . Following a single-blind placebo session , participants r and omly received P/S or S/P ( P=3 placebo ; S=3 scopolamine ( 4μg/kg ) sessions ) . Mood-state self-ratings ( Profile of Mood State ( POMS ) and Visual Analog Scales ( VAS ) ) and depression severity ( Montgomery-Åsberg Depression Rating Scale ( MADRS ) ) were obtained before each infusion . Day 1 ( baseline/placebo ) self-ratings were used in a discriminant function analysis to identify linear combinations of individual items that predict response . The discriminant analysis significantly separated responders from non-responders in both the unipolar and bipolar diagnostic subgroups . The discriminant functions accurately classified over 85 % of patients as responders/non-responders . The POMS depression subscale significantly correlated with clinical response , as did the VAS restlessness , sad , and irritated scales . These results indicate that self-report mood-ratings obtained before treatment can predict response outcome to scopolamine , and suggest that a constellation of mood-state features may be related to clinical response", "To determine whether nicotine dependence , classified by level of severity , was associated with other substance dependence , major depression , and anxiety disorders , we studied a r and om sample of 1007 young adults in the Detroit ( Mich ) area using the National Institute of Mental Health Diagnostic Interview Schedule , revised according to DSM-III-R. The systematic coverage of DSM-III-R criteria of nicotine dependence provides an unprecedented opportunity to separate persons with nicotine dependence from the larger class of persons with a history of smoking and to examine the prevalence of psychiatric disorders among persons with nicotine dependence and among nondependent smokers . The lifetime prevalence of nicotine dependence was 20 % . Nicotine dependence was associated with alcohol , cannabis , and cocaine dependence . Controlling for the effects of other substance dependencies , persons with nicotine dependence had higher rates of major depression and anxiety disorders . The strength of these associations varied by level of severity of nicotine dependence . Nondependent smokers had higher rates of other substance dependencies , but not of major depression or anxiety disorders", "Some antidepressant agents generate differential benefit based on gender . Blocking cholinergic muscarinic receptors using scopolamine produces robust and rapid antidepressant effects in males and females combined . This study evaluated if males and females differ in the antidepressant response magnitude following scopolamine administration . A total of 52 male and female out patients meeting criteria for recurrent major depressive or bipolar disorder participated in a double-blind , r and omized , placebo-controlled , crossover clinical trial involving seven i.v . infusions of placebo or scopolamine ( 4 μg/kg ) . Following a single-blind placebo lead-in , participants entered either a placebo-block/scopolamine-block or a scopolamine-block/placebo-block sequence . Each block included three sessions . Clinical ratings were acquired before each infusion and included the Montgomery – Asberg Depression Rating Scale ( MADRS ) and the Hamilton Anxiety Rating Scale ( HAM-A ) . A treatment group × block interaction ( F=21.0 , p in MADRS scores across gender , and the reduction was significant by the evaluation following the first scopolamine administration ( F=8.4 , p=0.006 ) . The treatment group × block interaction was also significant in males ( F=3.8 , p=0.043 ) and females ( F=35.6 , p that the response magnitude was larger in women . The treatment × block interaction was significant for the HAM-A across gender ( F=12.0 , p that the antianxiety response was greater in women . Men and women show a rapid antidepressant response following scopolamine , but the magnitude of response is larger in women than in men", "BACKGROUND We previously reported that intravenous ( IV ) scopolamine administration produced rapid and robust antidepressant effects in a sample consisting of both unipolar and bipolar depressives . The present study aim ed to replicate this finding in an independent sample limited to unipolar depressives . METHODS Out patients with major depressive disorder ( MDD ; n = 23 ; 22 were included in analyses ) participated in a double-blind , placebo-controlled , crossover trial . Subjects were r and omized into either a P/S or S/P sequence ( P = block of three placebo sessions ; S = block of three scopolamine sessions ; [ 4.0 microg/kg IV ] ) . Sessions occurred 3 to 5 days apart , such that time spent in each block lasted 1.5 to 2 weeks and the interval between blocks was 3 to 5 days . The Montgomery-Asberg Depression Rating Scale ( MADRS ) served as the primary outcome measure . RESULTS Following the initial block , the group receiving scopolamine first ( S/P ) showed a 32 % reduction in MADRS scores ( p placebo ( P/S ; p = .009 ) , confirming the a-priori hypothesis . Improvement was significant at the first evaluation that followed scopolamine administration ( p = .011 ) . In Block 2 , the P/S group showed a 53 % reduction in MADRS scores ( p = .001 ) following scopolamine versus placebo , whereas the reduction seen in S/P subjects who received scopolamine during Block 1 persisted as they received placebo during Block 2 . Scopolamine induced drowsiness , blurred vision , dry mouth , light-headedness , and reduced blood pressure , which were sufficiently well tolerated that no subject dropped out because of side effects . CONCLUSIONS These results replicate previous finding that scopolamine produces a rapid and robust antidepressant response", "In an intensive multidrug , multidose study , nine elderly depressed patients were administered 0.1 , 0.25 , and 0.5 mg of scopolamine hydrobromide , 1 mg of oral lorazepam , and placebo in a double-blind investigation aim ed at assessing the status of the central cholinergic nervous system in geriatric depression . Significant cognitive and behavioral effects of scopolamine were observed only at the high dose ( 0.5 mg ) , while lower doses and lorazepam showed no significant differences from placebo . Cognitive deficits caused by scopolamine were in the areas of new learning , access to semantic memory , vigilance , and continuous performance . Behavioral effects consisted of activation , restlessness , and anxiety , but there was no significant effect on depressed mood . These results suggest that elderly depressed patients with mild to moderate cognitive impairment seem to be more similar to previously studied elderly controls rather than to patients with Alzheimer 's disease in their reaction to short-term cholinergic blockade , and suggest that the cognitive and mood changes often seen in geriatric depression may involve factors other than disturbed muscarinic cholinergic mechanisms" ]	41189492-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Combined oral contraceptives ( COCs ) reduce levels of and rogen , especially testosterone ( T ) , by inhibiting ovarian and adrenal and rogen synthesis and by increasing levels of sex hormone-binding globulin ( SHBG ) . Although this suppressive effect has been investigated by numerous studies over many years , to our knowledge no systematic review concerning this issue had been performed . This systematic review and meta- analysis was performed to evaluate the effect of COCs on concentrations of total T , free T and SHBG in healthy women and to evaluate differences between the various types of COCs ( e.g. estrogen dose , type of progestin ) and the assays used to assess total T and free T. METHODS A review of the literature was performed using data base search es ( MEDLINE , EMBASE and the Cochrane Central Register of Clinical Trials ) and all publications ( from inception date until July 2012 ) investigating the effect of COCs on and rogen levels in healthy women were considered eligible for selection . Three review ers were involved in study selection , data extraction and critical appraisal . For the meta- analysis , data on total T , free T and SHBG were extracted and combined using r and om effects analysis . Additional subgroup analyses were performed to evaluate differences between the various types of COCs ( e.g. estrogen dose , type of progestin ) and the assays used to assess total T or free T. RESULTS A total of 151 records were identified by systematic review and 42 studies with a total of 1495 healthy young women ( age range : 18–40 years ) were included in the meta- analysis . All included studies were experimental studies and 21 were non-comparative . Pooling of the results derived from all the included papers showed that total T levels significantly decreased during COC use [ mean difference ( MD ) ( 95 % confidence interval , CI ) −0.49 nmol/l ( −0.55 , −0.42 ) ; P lower levels of free T were also found [ relative change ( 95 % CI ) 0.39 ( 0.35 , 0.43 ) ; P contrary , SHBG concentrations significantly increased during all types of COC use [ MD ( 95 % CI ) 99.08 nmol/l ( 86.43 , 111.73 ) ; P effects on total and free T compared with COCs with 30–35 µg EE . In addition , suppressive effects on T levels were not different when comparing different types of progestins . However , subgroup analyses for the estrogen dose and the progestin type in relation to changes in SHBG levels did show significant differences : COCs containing second generation progestins and /or the lower estrogen doses ( 20–25 µg EE ) were found to have less impact on SHBG concentrations . CONCLUSIONS The current literature review and meta- analysis demonstrates that COCs decrease circulating levels of total T and free T and increase SBHG concentrations . Due to the SHBG increase , free T levels decrease twice as much as total T. The estrogen dose and progestin type of the COC do not influence the decline of total and free T , but both affect SHBG . The clinical implication s of suppressed and rogen levels during COC use remain to be eluci date	[ "It is generally assumed that the oral contraceptives cause the carrier proteins to change . Notoriously this effect is used to evaluate indirectly their estrogenicity/gestagenicity ratio . In order to assess the residual intrinsic and rogenic activity of two new 19-nor-derivative components , Desogestrel ( DG ) 150 micrograms and Gestodene ( GD ) 75 micrograms , both in association with Ethinylestradiol ( EE ) 30 micrograms , Sex Hormone Binding Globulin , Thyroxine Binding Globulin , Ceruloplasmin and Free And rogen Index ( FAI ) , were studied in 40 young normally cycling healthy volunteers , matched for body mass index and age . The participants were r and omly assigned to either EE-DG or EE-GD treatment . A marked significant increase in all the carrier proteins was found . Conversely , the values for FAI decreased significantly . The changes in the two groups were substantially of the same magnitude . These results are an indirect confirmation of the well-known negligible receptor binding affinity of the two progestogen in vitro , also supporting for these compounds the lack of relevant and rogenic effects", "The effect of two oral contraceptive ( OC ) pills , both containing 150 micrograms of desogestrel , but with 20 ( Mercilon ) or 30 micrograms ( Marvelon/Desolett ) of ethinyl estradiol on plasma levels of lipids , lipoproteins and sex hormone binding globulin ( SHBG ) , total and free testosterone were compared in a double-blind , r and omized , two-center study in a total of 60 women over one year . A significant rise with Marvelon but not with Mercilon was seen in total cholesterol , HDL cholesterol , HDL-3 and apolipoprotein B , whereas LDL cholesterol decreased with Mercilon only . These effects result ed in significant differences between the two groups in the magnitude of responses in all these parameters except HDL-3 . HDL-2 , apolipoprotein A-1 and total phospholipids were elevated with both pills after treatment and with no difference in the degree of response between groups . The HDL/LDL cholesterol ratio tended to increase in both groups and that of apolipoproteins A-1/B in the women on Mercilon . Total triglycerides increased in both groups , but more in the women on Marvelon . Total testosterone decreased , particularly in the Marvelon group , whereas the two pills caused a similar increase in SHBG and decrease in free testosterone . It is concluded that the direction of changes in plasma lipids and lipoproteins with both these pills may as a whole be interpreted as beneficial , and that the differences in effect on LDL cholesterol and apolipoprotein B may suggest a slightly advantageous effect of Mercilon in this aspect . However , the clinical significance of these changes is uncertain . The results indicate a lack of and rogenicity of both pills", "This six-cycle , multicenter , open-label , r and omized study compared the clinical experience of two low-dose oral contraceptives ( OC ) : a triphasic OC containing norgestimate ( NGM ) and 35 micrograms ethinyl estradiol ( EE ) ( Ortho Tri-Cyclen ) and a monophasic OC containing norethindrone acetate ( NETA ) and 20 micrograms EE ( Loestrin Fe 1/20 ) . Cycle control , lipid and and rogen profiles , and user satisfaction were studied in new-start OC users ( i.e. , no prior use within 60 days ) . Breakthrough bleeding or breakthrough spotting ( BTB/BTS ) occurred in a significantly smaller percentage of NGM/EE users than NETA/EE users during each of six cycles ( p incidence of BTB/BTS ranged from 3.7 % to 13.5 % for NGM/EE users and from 23.5 % to 49.7 % for NETA/EE users . Significantly fewer NGM/EE users than NETA/EE users experienced absence of menses at cycles 2 through 6 ( p percentages of women having no menses at each cycle ranged from 0.9 % to 4.7 % for NGM/EE users and from 10.3 % to 21.3 % for NETA/EE users . NGM/EE users reported a significantly ( p level of satisfaction with their OC at the end of six cycles than did NETA/EE users , but there was no significant difference in compliance , discontinuation rates , or adverse events between the two groups . NGM/EE produced a significantly ( p beneficial effect on HDL-C , HDL2 , and apo A-I than did NETA/EE . No statistically significant treatment differences were found for total cholesterol , LDL-C , triglycerides , or apo-B. Both OC increased sex hormone binding globulin and decreased free testosterone , but NGM/EE had a significantly greater effect ( p < 0.009 )", "BACKGROUND Oral contraceptive is the most commonly used method of fertility control . Yasmin is a combination of a novel progestogen with anti- and rogenic and anti-mineralcorticoid activities ( 3 mg Drospirenone ( DRSP ) and 30 microg ethinylestradiol ( EE ) ) . It has been shown in many clinical trials that Yasmin is an efficacious oral contraceptive , lacking undesired effects as with other oral contraceptives such as weight gain . However the effects of Yasmin on sexual desire and libido have not been intensively investigated so far OBJECTIVE Investigate the effects of Yasmin on sexual desire , libido and changes in the free and rogen index ( FAI ) compare to Meliane ( 75 microg gestodene + 20 microg ethinylestradiol ) . MATERIAL AND METHOD The authors ' report the results of a double blind r and omized controlled study using a translated version of the Female Sexual Function Index question naire ( FSFI ) for the assessment of the sexual function . The free and rogen index was calculated from measurements of testosterone and sexual hormone binding globulin . RESULT The result shows statistically significant improvements regarding sexual desire , arousal and overall satisfaction in the Yasmin group . Additionally , an increased frequency of orgasms in the Meliane group was reported . Statistically significant differences between the two treatments regarding changes in the FSFI score and changes in the free and rogen index have not been observed . CONCLUSION The novel oral contraceptive containing drospirenone ( Yasmin ) and the non-anti- and rogenic progestin containing oral contraceptive ( Meliane ) do not show unfavorable effects on sexual response and libido", "The relationships between plasma free testosterone ( FT ) and measures of sexual attitude , sexual behavior , and gender role behavior were assessed in 55 oral contraceptive-using and 53 nonusing female undergraduates . Plasma FT and other measures of and rogenicity were substantially lower in the oral contraceptive ( OC ) group . Correlations between FT and certain behavioral and attitudinal measures were found in the OC users but not the nonusers . In the OC users , FT was positively associated with frequency of sexual intercourse but not with frequency of masturbation . It was negatively associated with restrictive sexual morality . Correlations between FT and measures of gender role behavior were negligible , and FT was unrelated to proceptivity , homosexual interest , or the use of sexual fantasy . The occurrence of some predicted correlations among pill-using women but not the nonusers requires explanation , particularly in view of the substantially lower levels of FT in the pill-using group . It is suggested that and rogen — behavior relationships in women are easily obscured by psychosocial influences and in this sample of young women such influences may have been more powerful among those not using OCs . Such psychosocial influences are likely to differ at different stages of women 's life cycles . The importance of controlling for such influences in any study of hormone — sexual behavior relationships in women is emphasized , and the need for prospect i ve studies of women before and after starting on steroidal contraception is recognized", "The aim of this study was to examine whether changes in plasma and rogen levels ( total testosterone ( T ) , free testosterone ( FT ) , and dehydro-epi and rosterone-sulfate ( DHEA-S ) ) induced by oral contraceptive ( OC ) use were related to changes in sexual interest or response or in mood . Sixty-one women provided blood sample s and were assessed , using interviews and st and ardized question naires , prior to starting , and after 3 months on OCs ( Ortho-Tricyclen , Ortho-Tricyclen-Lo , or Ortho-Cyclen , all containing the same progestagen , norgestimate ) . Significant decreases in T , FT , and DHEA-S were found after 3 months , although the extent of reduction was variable across women . There was some support for a relationship between the degree of reduction in total T and FT and the frequency of sexual thoughts after 3 months on OCs . However , some women had no loss of sexual interest in spite of substantial reduction in FT , and there was overall no evidence that reduction in FT affected enjoyment of sexual activity with a partner . The findings are consistent with the idea that some women may be more sensitive to changes in T than others . No relationship was found between negative mood , as assessed by the Beck Depression Inventory , and changes in T , FT , or", "OBJECTIVE To compare complications of third and second generation oral contraceptive pills ( OCPs ) . METHODS In a r and omized clinical trial from October 2007 to October 2008 , 100 healthy women of reproductive age referred to Amir Hospital Family Planning Clinic and some heath centers in Semnan , Iran were r and omized in 2 equal groups . They received either a third generation OCP ( 150 microgram desogestrel [ DSG ] + 30 microgram ethinylestradiol [ EE ] ) or a second generation type ( 150 microgram levonorgestrel [ LNG ] + 30 microgram EE ) . Six months later , changes of weight , acne , and hirsutism severity , as well as serum titers of sex hormone-binding globulin ( SHBG ) and free testosterone were compared between the 2 groups . RESULTS Forty-five women were evaluated in the DSG+EE OCP group , and 46 women in the LNG+EE OCP group . The BMI was significantly higher in the second group ( p=0.000 ) after 6 months duration . Likewise , the decrement of acne and hirsutism severity was significantly higher in the DSG+EE users ( p=0.000 ) . Mean changes of serum free testosterone ( p=0.967 ) and SHBG ( p=0.916 ) were comparable between the 2 groups . CONCLUSION In comparison with the LNG+EE OCP , the DSG+EE OCP is a contraceptive pill that significantly decreases the severity of acne and hirsutism , without any significant change in weight", "The relationship between plasma testosterone ( T ) secretion and patterns of sexual behavior was examined in 18 women using oral contraceptives ( OCs ) and 13 nonusers matched for partner availability . Retrospective assessment s of perimenstrual symptoms , sexual attitudes , and sexual experience were obtained and women completed daily ratings of the frequency of sexual activities and the level of well-being for 1 month . Plasma levels of sex hormone binding globulin ( SHBG ) , progesterone , Total T , Free T , and non-SHBG bound T were determined by radioimmunoassay at four phases of the pill or menstrual cycle . Overall , women not using OCs had higher plasma levels of Total , Free , and non-SHBG bound T and lower plasma levels of SHBG than those of OC users . Further , only nonusers had perimenstrual decreases in plasma levels of Total and Free T. The two groups were comparable on most retrospective measures . However , OC users reported more satisfaction with their sexual partners than did nonusers and prospect i ve monitoring revealed that they engaged in sexual interactions more frequently than did nonusers across the cycle . In contrast , both groups reported a similar frequency of autosexual activities across the cycle . There were no correlations between average levels of T and levels of sexual desire , sexual interactions , or autosexuality . Moreover , only nonusers reported a decrease in levels of sexual desire during the perimenstrual period that was associated with the changes in Free T over the menstrual cycle", "The effects of different monophasic combinations of ethinyl estradiol and norethindrone on FSH , LH , sex hormone binding globulin , total testosterone , and rostenedione , and dehydroepi and rosterone sulfate levels in non-obese , non-hirsute women were compared . Retrospective analysis of frozen serum from a prospect i ve r and omized trial in which women received one of three oral contraceptive pills containing ethinyl estradiol 50 micrograms/norethindrone 1 mg , ethinyl estradiol 35 micrograms/norethindrone 1 mg or ethinyl estradiol 35 g/norethindrone 0.5 mg for nine cycles was conducted . Blood sample s were obtained prior to treatment and during the third , sixth and ninth pill cycles . Ethinyl estradiol 50 micrograms/norethindrone 1 mg and ethinyl estradiol 35 micrograms/norethindrone 1 mg suppressed FSH , LH , and total testosterone and increased sex hormone binding globulin to a similar degree . Ethinyl estradiol 35 micrograms/norethindrone 0.5 mg result ed in less suppression of FSH , LH , and total testosterone , but greater elevation of sex hormone binding globulin . Dehydroepi and rosterone sulfate was suppressed to a similar degree with ethinyl estradiol 35 micrograms/norethindrone 1 mg and ethinyl estradiol 35 micrograms/norethindrone 0.5 mg , but ethinyl estradiol 50 micrograms/norethindrone 1 mg result ed in the least suppression of dehydroepi and rosterone sulfate . Ethinyl estradiol 35 micrograms/norethindrone 1 mg caused greater suppression of and rostenedione than did the other two oral contraceptives . Oral contraceptive-induced changes in gonadotropins , and rogens , and sex hormone binding globulin can be predicted by considering the relative amounts of estrogen and progestin in the pill . When combined with 1 mg of norethindrone , 50 micrograms of ethinyl estradiol did not result in greater suppression of FSH , LH , or total testosterone or in greater elevation of sex hormone binding globulin than did 35 micrograms of ethinyl estradiol ", "Oral contraceptives ( OC ) suppress excess and rogen production ; however , different progestins in combination with low-dose estrogens produce divergent effects on sex hormone-binding globulin ( SHBG ) and testosterone that may influence clinical outcomes . This multicenter , open-label , r and omized study compared biochemical and rogen profiles and clinical outcomes associated with two OC containing the same amounts of ethinyl estradiol ( EE , 20 micrograms ) but different progestins , levonorgestrel ( LNG , 100 micrograms ) , and norethindrone acetate ( NETA , 1000 micrograms ) . Fifty-eight healthy women ( 18 - 28 years old ) received three cycles of treatment with LNG/EE ( n = 30 ) or NETA/EE ( n = 28 ) . The results showed that LNG reduced and rogen levels in three compartments -- adrenal , ovarian , and peripheral . NETA reduced only adrenal and peripheral and rogens . Despite a 2.2-fold greater relative increase in SHBG with NETA than LNG , bioavailable testosterone ( T ) was reduced by the same amount with LNG and NETA . Both treatments improved acne and were well tolerated . Low-dose OC ( EE , 20 micrograms ) are effective in reducing circulating and rogens and acne lesions without causing weight gain . Although LNG and NETA affected secondary markers differently , both OC formulations produced an equivalent decrease in bioavailable", "BACKGROUND Since very little research in this field is available , this study aims to assess the role of psychosexual , relationship , hormonal and genetic measures in the sexual desire of users of three hormonal contraceptive products [ low-dose combined oral contraceptive ( 20 mcg ethinylestradiol/150 mcg desogestrel ) , progestin-only pill ( 75 mcg desogestrel ) and vaginal ring ( daily dose of 15 mcg ethinylestradiol/120 mcg etonogestrel ) ] . STUDY DESIGN Fifty-five couples were r and omized over three groups in which the women consecutively used each product during 3 months . Both partners repeatedly filled out question naires on solitary and dyadic sexual desire ( desire to behave sexually by oneself or towards a partner ) . Total and free testosterone , sex hormone binding globulin and a genetic marker of and rogen receptor sensitivity [ cytosine-adenine-guanine ( CAG ) repeat length ] were assessed on blood sample s of the female partners . RESULTS Sexual desire was higher in women with either short or long CAG repeats ( solitary , p=.004 ; dyadic , p=.008 ) . Desire levels were higher during vaginal ring use ( solitary , p=.018 ; dyadic , p=.007 ) . The woman 's mood was found to impact her dyadic sexual desire ( p sexual desire ( p<.001 ) . CONCLUSIONS The current study found evidence for a role of and rogen receptor sensitivity and mood in the sexual desire of hormonal contraceptive users", "In this study , hormone profiles were studied using Diane 35 and Diane 50 before and after treatment for 4 - 25 months . A comparison of the hormone profiles with Diane 35 or Diane 50 should investigate , if both preparations induce complete ovarian suppression , independent of the given dose of ethinyl oestradiol . 43 patients were treated with Diane 35 and 15 women with Diane 50 over a different lengths of time -- up to a period of 25 cycles . Parallel to the determination of the hormone profiles ( luteinising hormone [ LH ] , follicle stimulating hormone [ FSH ] , prolactin , oestrone [ E1 ] , oestradiol [ E2 ] , progesterone , total testosterone [ T. T. ] , free testosterone [ F. T. ] , dehydroepi and rosterone-sulfate [ DHEA-S ] , delta-4- and rostenedione [ A. ] and sex hormone binding globulin [ SHBG ] ) , observations on the and rogen symptoms before treatment and their course during therapy were made . Moreover , the ratios of LH/FSH and E1/E2 as well as the and rogenic index , the ratio of total testosterone/SHBG were determined as control of treatment effects . The most important hormonal changes , which had been observed during a period up to two years are the following : --LH and FSH suppression -- prolactin with increasing tendency -- decrease of the total and rogens and free testosterone-- decrease of the oestrogens E1 , E2 - -increase of SHBG . The confirmation of the efficacy of the anti- and rogen/oestrogen combination was reflected by the decline of the and rogenic index in all groups . Acne and seborrhoe improved after 3 - 4 cycles ; alopecia after 8 - 9 cycles and hirsutism diminished after 3 cycles of treatment . In spite of different doses of the combined preparations with 2 mg cyproteronacetate and 0.035 or 0.050 mg ethinyloestradiol , no difference in ovarian suppression as well clinical effects could be found", "AIM This 12-month study was conducted to evaluate the skeletal effects of two monophasic oral contraceptives containing 20 mug of ethinylestradiol and 100 mug of levonorgestrel ( LEVO ) or 150 mug of desogestrel ( DESO ) . METHODS Fifty-two women ( 18 - 24 years ) were r and omized into the DESO group or the LEVO group ; 36 women served as controls . The areal bone mineral density ( aBMD ) of the femoral neck and the lumbar spine was evaluated by DXA , and parameters of bone geometry and volumetric bone mineral density ( vBMD ) were assessed by peripheral quantitative computed tomography at the distal radius and the tibia . RESULTS The LEVO group did not lose vertebral aBMD , whereas women in the DESO group lost 1.5 % . At the distal radius and the tibia ( shank level , 14 % ) , LEVO induced an increase in total cross-sectional area , indicating increased periosteal bone formation . Radial trabecular vBMD declined by 1.4+/-1.8 % in the DESO group , while it remained unchanged in the LEVO group . CONCLUSION Our study suggests that the skeletal effects of OC preparations may be influenced by progestogenic components in young women", "A r and omised cross-over trial was performed to compare the pharmacodynamic actions of three low-dose oral contraceptives ( OCs ) : Marvelon ( 150 micrograms desogestrel (DSG)+ 30 micrograms ethinyloestradiol ( EE ) ) , Mercilon ( 150 micrograms DSG + 20 micrograms EE ) and Microgynon ( 150 micrograms levonorgestrel ( LNG ) + 30 micrograms EE ) . None of the OCs produced any significant changes in serum cholesterol , LDL-C and apoprotein B. Triglycerides were increased by the desogestrel OCs but not by Microgynon . The latter however increased the glucose and insulin responses to a glucose tolerance test whereas Marvelon and Mercilon had no effect . HDL-C increased with Marvelon , was unchanged with Mercilon and was decreased with Microgynon . Apoprotein AII was increased by all three OCs but only the DSG OCs increased apoprotein AI . All OCs produced similar increases in caeruloplasmin but the increase in SHBG was much greater with Marvelon and Mercilon than with Microgynon . Testosterone was reduced more with Microgynon than with the DSG OCs . Many of the changes reflect the strong anti-oestrogenic action of LNG on metabolic parameters compared to DSG . Except for the effect on HDL-C , there was little difference between Marvelon and Mercilon on metabolic parameters and this complements the findings from large-scale clinical trials of the two OCs . Mercilon , therefore provides a very satisfactory alternative to Marvelon", "INTRODUCTION A new oral contraceptive containing the natural estrogen estradiol and a 19-nortestosterone derivate dienogest ( DNG ) in a four-phasic 28-day regimen may be used by women . AIM To investigate the quality of sexual life of healthy women on estradiol valerate and DNG ( E2V/DNG ) oral contraceptive . METHODS Fifty-seven women ( age range 18 - 48 years ) were enrolled . The Short Form-36 ( SF-36 ) question naire to assess quality of life ( QoL ) was administered at baseline and at the 26th day of both the 3rd and 6th cycles of oral contraceptive ( OC ) intake . The Short Personal Experience Question naire ( SPEQ ) to measure the change of sexual behavior was used at the 2nd , 7th , 14th , 21st , 26th , and 28th days of the baseline cycle , as well as at the same days of both the 3rd and 6th cycle of contraceptive intake . MAIN OUTCOME MEASURE The SF-36 and the SPEQ question naires . RESULTS Women reported QoL improvement at the 3rd ( P improvement of sexuality during the 3rd and the 6th cycle with respect to baseline experience was observed ( P frequency of sexual activity remained basically unchanged ( P = NS ) . Enjoyment and desire improved at the 6th cycle with respect to the 3rd cycle ( P dyspareunia at the 3rd and 6th cycles ( P desire , arousal , orgasm , enjoyment , and sexual activity improved , reaching a peak around the 14th day of the menstrual cycle ( P sexually cyclic , but the peak improvement of desire , arousal , orgasm , enjoyment , and sexual activity appeared around the 7th day of OC intake ( P E2V/DNG multiphasic extended regimen has been found to positively modify the sexuality of users", "And rogen deficiency in women is increasingly recognized as a new clinical syndrome and has raised our awareness of the importance of accurate and well-vali date d measurements of serum free testosterone ( T ) concentrations in women . Therefore , we compared serum free T levels measured by equilibrium dialysis to those measured by a direct RIA ( analog method ) and to those calculated from the law of mass action ( requires the measurement of total T and SHBG ) . We also calculated the free and rogen index , 100 x T/SHBG , as a simple index known to correlate with free T. Subjects were 147 women with variable and rogen and estrogen statuses . All were studied three times in 1 month and included women 1 ) with regular menses ( estrogen positive , T positive ) , 2 ) more than 50 yr old and not receiving estrogen ( estrogen negative , T positive ) , 3 ) receiving estrogen ( estrogen positive , T negative ) , and 4 ) with severe and rogen deficiency secondary to hypopituitarism ( estrogen negative , T negative ) . Calculated values for free T using the laws of mass action correlated well with those obtained from equilibrium dialysis ( r = 0.99 ; P total T and SHBG . In contrast , the direct RIA method had unacceptably high systematic bias and r and om variability and did not correlate as well with equilibrium dialysis values ( r = 0.81 ; P of detection was higher for the direct RIA than for equilibrium dialysis or calculated free T. Free and rogen index correlates well with free T by equilibrium dialysis ( r = 0.93 ; P < 0.0001 ) , but is a unitless number without reference to the physical reality of free T. We conclude that the mass action equation and equilibrium dialysis are the preferred methods for use in diagnosing and rogen deficiency in women", "The pharmacokinetics of levonorgestrel ( LNG ) and ethinylestradiol ( EE2 ) were determined in 14 healthy women ( age 18 to 27 years ) during a treatment period of three months with a tri-step combination oral contraceptive ( Triquilar ) . Prior to this treatment period , the same women received a single administration of a coated tablet containing 0.125 mg LNG together with 0.03 mg EE2 . There was a washout phase of one week between both treatments . Following single dose administration , a mean terminal half-life of 22 h was observed for LNG . The total clearance was 1.0 ml x min-1 x kg-1 and the volume of distribution was 128 l. During a treatment cycle , LNG levels in the serum accumulated by a factor of about four as compared to single dose administration . Steady-state drug levels were reached during the second half of each cycle . As compared to single dose administration , the following changes were observed for LNG at the end of treatment cycles one and three : reduced total ( 0.5 ml x min-1 x kg-1 ) and free clearance ( 50 ml x min-1 x kg-1 ) and a reduced volume of distribution ( 52 l ) . A concomitant increase in the SHBG concentrations by a factor of two as compared to pretreatment values was observed during treatment and appeared to be mainly responsible for the changes in the pharmacokinetics of LNG . Marked changes were also seen for the serum protein binding of LNG . After single dose administration , the free fraction of LNG was 1.4 % and the fractions bound to SHBG and albumin were 55.0 % and 43.6 % , respectively . At the end of cycle one , the free fraction was only 1.0 % and the fractions bound to SHBG and albumin were 69.4 % and 30.0 % , respectively . There was no difference in corresponding pharmacokinetic parameters and in the serum protein binding of LNG at the end of cycles one and three . On the last day of treatment cycles one and three , the AUC(0 - 4h ) values of EE2 were 331.2 and 369.6 pg x ml-1 x h , respectively , which corresponds to an about 11 - 24 % increase as compared to single dose administration , where an AUC(0 - 4h ) value of 298.3 pg x ml-1 x h was found . Total and free testosterone concentrations decreased during treatment cycles one and three by about 41 % and 55 % , respectively , compared with the corresponding values measured prior to treatment", "Changes in endogenous and rogen metabolism were compared in healthy women taking one of four low-dose modern oral contraceptives ( OCs ) . One hundred women were r and omized to ( 1 ) 35 micrograms ethinyl estradiol ( EE ) + 250 micrograms norgestimate ( Cilest ) ; ( 2 ) 20 micrograms EE + 150 micrograms desogestrel ( Mercilon ) ; ( 3 ) 30 micrograms EE + 150 micrograms desogestrel ( Marvelon ) ; or ( 4 ) 30 micrograms EE + 75 micrograms gestodene ( Femodene ) . During the luteal phase of the pretreatment cycle , body weight and blood pressure were recorded , and plasma levels of the following variables were recorded : sex-hormone-binding globulin ( SHBG ) , cortisol-binding globulin ( CBG ) , testosterone , free testosterone , dihydrotestosterone , and rostenedione , dihydroepi and rosterone sulfate ( DHEAS ) , and hydroxyprogesterone . The free and rogen index was also calculated . These variables were remeasured during the third week of OC intake and during the fourth and sixth cycles . There were no statistically significant differences in and rogenic variables among the four OCs . The DHEAS concentration decreased less with the 20 micrograms EE + desogestrel formulation compared with either 30 micrograms EE + desogesterel or norgestimate-containing formulations ( 20 % vs. 45 % ) . Concentrations of SHBG and CBG increased significantly in all four groups ( average 263 + /- 119 % and 94 + /- 26 % , respectively ) ; CBG increased less in women taking 20 micrograms EE + desogestrel ( about 75 % ) than in the other formulations ( about 100 % ) . The four modern , low-dose OCs tested had similar impacts on endogenous and rogen metabolism , yielding significant decreases in testosterone , dihydrotestosterone , and rostenedione , and DHEAS . All of these formulations may be beneficial in women with and rogen-related syndromes such as acne and hirsutism . Large studies are under way to establish which of the third-generation OCs is the least and rogenic . In vitro studies suggest that norgestimate has the least and rogenic profile", "The aim of the present study was to compare changes in the endogenous and rogen environment in healthy women while on low-dose oral contraceptives ( OCs ) . One-hundred healthy women were r and omized to receive one of four OCs during six months : 21 tablets of Cilest , Femodeen , Marvelon , or Mercilon . During the luteal phase of the pretreatment cycle , body weight and blood pressure were recorded and the following parameters were measured : sex hormone-binding globulin ( SHBG ) , corticosteroid-binding globulin ( CBG ) , testosterone ( T ) , free testosterone ( FT ) , 5 alpha-dihydrotestosterone ( DHT ) , and rostenedione ( A ) , dehydroepi and rosterone-sulphate ( DHEA-S ) and 17 alpha-hydroxyprogesterone ( 170HP ) while also the free and rogen index ( FAI ) was calculated . Measurements were repeated during the 3rd week of pill intake in the 4th and the 6th pill month . There were no differences on body mass and blood pressure with the use of the four OCs . The mean serum DHEA-S decreased significantly in all groups though less in the Mercilon group when compared to Cilest and Marvelon ( approximately 20 % vs 45 % ) . Mean serum SHBG and CBG increased significantly in all four groups approximately 250 % and 100 % , respectively . In each group CBG also increased significantly but less in women taking Mercilon ( -75 % ) as compared to the others ( -100 % ) . Current low-dose OCs were found to have similar impact on the endogenous and rogen metabolism with significant decreases of serum testosterone , DHT , A , and DHEA-S. They may be equally beneficial in women with and rogen related syndromes such as acne and hirsutism", "Circulating concentrations of sex hormone-binding globulin ( SHBG ) are increased by use of oral estrogen . The objective of this study was to determine whether postmenopausal women who used oral estrogen had higher serum concentrations of SHBG and lower serum concentrations of free testosterone ( T ) than nonusers , and whether free T was associated with lean body mass , particularly skeletal muscle mass . Subjects were 70 postmenopausal women , 46 - 55 yr old , 46 of whom used oral estrogen . Total and regional body composition were determined by dual-energy x-ray absorptiometry . Serum concentrations of SHBG , total T , and estradiol ( E(2 ) ) were determined by RIA . Free T was calculated from concentrations of total T and SHBG . Hormone users had higher serum concentrations of E(2 ) and SHBG ( 182.0 + /- 58 . 5 vs. 82.9 + /- 41.1 nmol/L , mean + /- SD , P : free T ( 3.7 + /- 2.2 vs. 7.9 + /- 4.1 pmol/L , mean + /- SD , P : total T did not differ . Total lean mass and leg lean mass were significantly correlated with free , but not total T [ r values of 0.29 ( P : arm lean mass was not correlated with either measure of T. Serum E(2 ) was significantly correlated with SHBG ( r = 0.50 , P : T ( r = -0.33 , P : oral estrogen therapy may accelerate or augment lean mass loss among postmenopausal women . This conclusion awaits confirmation by longitudinal observation", "OBJECTIVE RIA-based sex hormone measurements offer only limited precision and specificity in the low concentration range of women . Therefore , we aim ed to establish age-specific reference ranges for serum sex hormone concentrations in women using mass spectrometry and quantile regression . METHODS AND RESULTS Data from 985 women aged 20 - 80 yr , recruited for the prospect i ve Study of Health in Pomerania , were included in the analyses . Quantile regressions models were performed to calculate the age-specific 2.5th and 97.5th percentiles for sex hormone concentrations in women . Serum total testosterone ( TT ) and and rostenedione ( AD ) concentrations were measured by liquid chromatography-t and em mass spectrometry . Measured concentrations of SHBG and TT were used to calculate free testosterone ( free T ) . TT , AD , and free T concentrations showed a distinct age-related decline across 10-yr age groups ( one way ANOVA P hormone reference ranges for TT , AD , and free T were determined across each single year of age and for 10-yr age groups . Reference ranges over the whole age range of 20 - 80 yr were 0.35 - 1.97 nmol/liter for TT , 0.89 - 4.56 nmol/liter for AD , and 0.0025 - 0.0253 nmol/liter for free T. Separate reference ranges were provided for pre- and postmenopausal women as well as after inclusion of women using oral contraceptives or hormone therapy ( n = 1357 ) . CONCLUSION This is the first study to establish age-specific reference ranges for liquid chromatography-t and em mass spectrometry-measured TT and AD and calculated free T concentrations based on quantile regression analyses , accurately accounting for the observed low concentration range and the strong age dependency of these sex hormones in women", "BACKGROUND This study was conducted to compare the effects of two contraceptive pills with different doses of the same components , on plasma and rogen levels and female sexual function among women without previous sexual dysfunction . STUDY DESIGN The participants were r and omized into two groups , to receive pills containing ethynylestradiol ( EE ) 30 mcg and levonorgestrel ( LNG ) 150 mcg or EE 20 mcg and LNG 100 mcg , for six cycles . Sexual function was assessed using a st and ardized question naire [ Female Sexual Function Index ( FSFI ) ] . Hormone assays were performed at baseline and after the sixth cycle . RESULTS Forty-nine women were included in the EE30/LNG150 group and 48 in the EE20/LNG100 group . EE30/LNG150 group presented 54 % and 67 % decreases of total testosterone and free and rogen index , respectively , with statistical significance . EE20/LNG100 presented reductions of 20 % and 42 % , respectively , but without statistical significance . Both groups showed improvements in the FSFI \" desire \" score , but with statistical significance only for EE20/LNG100 group . CONCLUSIONS EE30/LNG150 decreased plasma and rogen levels , but there was no impairment in sexual desire , on the other h and , sexual desire score increased with EE20/LNG100 formulation", "OBJECTIVE The purpose of this study was to compare biochemical and rogen profiles in women treated with the contraceptive patch versus an oral contraceptive ( OC ) . STUDY DESIGN Twenty-four healthy women were r and omly assigned to receive 3 cycles of either the contraceptive patch ( ethinyl estradiol [ EE ] 20 microg/d and norelgestromin 150 microg/d ) or OC ( EE 35 mug and norgestimate 250 microg ) . Blood sample s were taken at baseline and end of treatment . Serum levels of sex hormone-binding globulin ( SHBG ) , total testosterone ( T ) , and rostenedione ( A ) , dehydroepi and rosterone sulfate ( DHEAS ) , dihydrotestosterone ( DHT ) , and 3alpha- and rostanediol glucuronide ( 3alpha-diol G ) were quantified by immunoassay methods ; free T was calculated . The paired t and Student t tests were used for statistical analysis . RESULTS Nineteen women completed the study ( patch , n = 10 ; OC , n = 9 ) . Despite a 1.6-fold relative increase in SHBG levels with the patch versus OC ( 449 % vs 274 % , P = .03 ) , free T decreased equally in both groups ( patch 60 % , P DHEAS decreased by 26 % in the patch group ( P 3alpha-diol G was reduced by 52 % in the patch group ( P OC was associated with significant decreases in A and DHT . CONCLUSION The contraceptive patch had an effect comparable to the OC on several key and rogenic markers . Given these biochemical findings , the contraceptive patch has significant potential as a therapeutic agent for disorders of and rogen excess", "CONTEXT There is no st and ardized assay of testosterone in women . Liquid chromatography mass spectrometry ( LC/MS ) has been proposed as the preferable assay by an Endocrine Society Position Statement . OBJECTIVE The aim was to compare assay results from a direct RIA with two LC/MS . DESIGN AND SETTING We conducted a blinded laboratory study including masked duplicate sample s at three laboratories -- two academic ( University of Virginia , RIA ; and Mayo Clinic , LC/MS ) and one commercial ( Quest , LC/MS ) . PARTICIPANTS AND INTERVENTIONS Baseline testosterone levels from 596 women with PCOS who participated in a large , multicenter , r and omized controlled infertility trial performed at academic health centers in the United States were run by varying assays , and results were compared . MAIN OUTCOME MEASURE We measured assay precision and correlation and baseline Ferriman-Gallwey hirsutism scores . RESULTS Median testosterone levels were highest with RIA . The correlations between the blinded sample s that were run in duplicate were comparable . The correlation coefficient ( CC ) between LC/MS at Quest and Mayo was 0.83 [ 95 % confidence interval ( CI ) , 0.80 - 0.85 ] , between RIA and LC/MS at Mayo was 0.79 ( 95 % CI , 0.76 - 0.82 ) , and between RIA and LC/MS at Quest was 0.67 ( 95 % CI , 0.63 - 0.72 ) . Interassay variation was highest at the lower levels of total testosterone ( ≤50 ng/dl ) . The CC for Quest LC/MS was significantly different from those derived from the other assays . We found similar correlations between total testosterone levels and hirsutism score with the RIA ( CC=0.24 ) , LC/MS at Mayo ( CC=0.15 ) , or Quest ( CC=0.17 ) . CONCLUSIONS A testosterone RIA is comparable to LC/MS assays . There is significant variability between LC/MS assays and poor precision with all assays at low testosterone levels", "The effects of the oral contraceptive combinations 0.125 mg Org 2969 ( desogestrel ) ( 13-ethyl-11-methylene-18,19-dinor-17alpha-pregn-4-en-20-yn-17-ol ) + 0.05 mg ethinyloestradiol ( EE ) and 0.125 mg levonorgestrel + 0.05 mg EE on serum sex-hormone-binding globulin ( SHBG ) , ceruloplasmin , transcortin and ratio free testosterone over total testosterone ( percentage free testosterone ) and ratio free 5alpha-dihydrotestosterone over total 5alpha-dihydrotestosterone ( percentage free 5alpha-dihydrotestosterone ) were compared in healthy female volunteers . Treatment was r and omly distributed over the volunteers ; 11 women received Org 2969 + EE and 11 women received levonorgestrel + EE . These combinations induced similar increases in transcortin levels ( 115 and 140 % ) and ceruloplasmin levels ( 115 and 123 % ) after 3 months of treatment . However , the combination Org 2969 + EE induced a substantial increase ( 213 % ) in SHBG capacity after 3 months of treatment , whereas a smaller increase ( 80 % ) was observed with levonorgestrel + EE . A return to pretreatment values was observed 2 months after termination of treatment for all parameters . The difference in the effects of both preparations oh SHBG was statistically significant and can be best explained by a difference in the and rogenicity of the progestogens . A good correlation was free testosterone and the reciprocal value of the percentage free 5 alpha-dihydrotestosterone . These results confirm that SHBG is the major regulator of the biologically active free and rogen fraction in women before , during and after combined oral contraceptive treatment", "In a double-blind , controlled , r and omized , four-arm , bicentric clinical study , the effect of four oral contraceptives ( OCs ) on various hormone parameters and serum-binding globulins was investigated . Four groups with 25 volunteers each ( 18 - 35 years of age ) were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinylestradiol ( EE ) + 2 mg dienogest ( DNG ) ( 30EE/DNG ) , 20 microg EE + 2 mg DNG ( 20EE/DNG ) , 10 microg EE + 2 mg estradiol valerate ( EV ) + 2 mg DNG ( EE/EV/DNG ) or 20 microg EE + 100 microg levonorgestrel ( LNG ) ( EE/LNG ) . The study was completed by 91 subjects . Blood sample s were taken after at least 12 h of fasting on Day 21 - 26 of the preceding control cycle and on Day 18 - 21 of the first , third and sixth treatment cycle . The serum concentrations of free testosterone were significantly decreased by about 40 - 60 % in all four groups , while those of dehydroepi and rosterone sulfate ( DHEAS ) showed a time-dependent decrease during treatment . Except for EE/EV/DNG , which increased prolactin significantly during the third and sixth cycles , no change was observed with the EE-containing preparations . There was a significant increase in the levels of serum-binding globulins during treatment , which differed according to the composition of the OCs used . The rise in sex hormone-binding globulin ( SHBG ) was highest during intake of 30EE/DNG ( + 320 % ) and lowest with EE/LNG ( + 80 % ) , while the effect of 20EE/DNG and EE/EV/DNG was similar ( + 270 % ) . The thyroxine-binding globulin ( TBG ) levels increased significantly , by 50 - 60 % , during treatment with the DNG-containing formulations , while the effect of EE/LNG was less significant ( + 30 % ) . The rise in corticosteroid-binding globulin ( CBG ) , which occurred in all groups , was most pronounced in women treated with 30EE/DNG ( + 90 % ) and least with EE/EV/DNG ( + 55 % ) , indicating a strong influence of EE and no effect of the progestogen component . In all treatment groups , the frequency of intracyclic bleeding rose in the first treatment cycle and decreased thereafter . Cycle control was significantly better with 30EE/DNG or EE/LNG than with 20EE/DNG or EE/EV/DNG . There was no significant change in blood pressure , body mass index or pulse rate throughout the study . In conclusion , the DNG-containing OCs caused a higher rise in SHBG and TBG levels than the LNG-containing preparation . The effects on CBG suggest a lesser hepatic effect of 2 mg EV as compared to 20 or 30 microg EE . In contrast to EE , the use of estradiol in OCs appeared to increase prolactin release , while the cycle control was better with the OC containing 30 microg EE", "ABSTRACT Objectives To compare the effects of two monophasic combined oral contraceptives , containing either nomegestrol acetate/17β-oestradiol ( NOMAC/E2 ) or levonorgestrel/ ethinylestradiol ( LNG/EE ) on endocrine function , and rogens , and sex hormone-binding globulin ( SHBG ) . Methods R and omised , open-label , multi-centre trial involving 121 healthy women , aged 18–50 years old . Participants received NOMAC/E2 ( 2.5 mg/1.5 mg ) in a 24/4-day regimen ( n = 60 ) or LNG/EE ( 150 μg/30 μg ) in a 21/7-day regimen ( n = 61 ) for six cycles . The primary outcome was the change from baseline to cycle 6 in markers of adrenal and thyroid function , and rogens , and SHBG . Results Total cortisol , corticosteroid-binding globulin ( CBG ) , and thyroxine-binding globulin ( TBG ) increased from baseline in both groups , with significantly greater increases in the LNG/EE group . No relevant changes from baseline or differences between the groups were observed for thyroid-stimulating hormone ( TSH ) and free thyroxine ( T4 ) . And rogens and and rogen precursors decreased from baseline in both groups , with significantly greater decreases in the LNG/EE group ( except for free testosterone ) . A greater increase in SHBG was observed with NOMAC/E2 than with LNG/EE . Conclusions NOMAC/E2 has significantly less influence on markers of adrenal and thyroid function and and rogens than LNG/EE . The clinical relevance of these findings requires further study", "In this study , we vali date d measurements of free testosterone ( fT ) and free estradiol ( fE(2 ) ) concentrations calculated from total serum concentrations of testosterone ( T ) , estradiol ( E(2 ) ) , and sex hormone-binding globulin ( SHBG ) , measured by direct , commercial radioimmunoassays , by comparison with reference measurements obtained by dialysis plus an in-house radioimmunoassay after extraction and chromatographic purification . The study was conducted in serum sample s from 19 postmenopausal women who were part of an ongoing prospect i ve cohort study . We also performed sensitivity analyses to examine the robustness of the theoretical calculations . Sensitivity analyses showed that in this population , competitive binding of dihydrotestosterone and total T could be ignored in the calculation of fE(2 ) , and competitive binding by dihydrotestosterone does not need to be taken into account for calculation of fT. Furthermore , variations in albumin and SHBG concentrations had negligible effects on fT and fE(2 ) calculations . Values of fT and fE(2 ) , calculated from total T and E(2 ) concentrations obtained by the same in-house radioimmunoassay used for the dialysis method , correlated highly with the measurements by dialysis ( Pearson 's coefficients of correlation above 0.97 ) . When calculating fT and fE(2 ) using total T and total E(2 ) concentrations obtained by different direct radioimmunoassays , almost all kits gave good correlations with the reference method for fT ( Pearson 's r > 0.83 ) , but only a few gave good correlations for fE(2 ) ( Diagnostic System Laboratories and DiaSorin ; r > 0.80 ) . The direct radioimmunoassays giving the best correlation for fT and fE(2 ) with the dialysis method were those that best measured total concentrations of T and E(2 ) . Furthermore , mean values of fT and fE(2 ) corresponded well to mean values by the reference method if SHBG measurements were also well calibrated . We conclude that in postmenopausal women , theoretical calculations are valid for the determination of fT and fE(2 ) concentrations and can give reliable estimation of cancer risk in epidemiological studies when the total concentrations of T , E(2 ) , and SHBG are measured accurately", " Twenty-six healthy , non-hirsute women had antecubital venous blood obtained before and during treatment with various contraceptive steroids for the measurement of dehydroepi and rosterone sulfate ( DHEA-S ) . Six of the women were r and omized to receive Ortho Novum 1/35 ( O/N ) , 7 were assigned to Ovcon 35 ( OV ) , and another five received Nordette ( N ) . The 6 women ingesting O/N as well as the 7 receiving OV had significant decreases in serum concentrations of DHEA-S ( p less than 0.05 ) . The percentage of decrease in DHEA-S in the O/N group ( 39 + /- 6 % ) and in the OV group ( 30 + /- 5 % ) was not statistically different . The group receiving N showed no changes from baseline measurements . Serum sample s from another 8 women who had received subcutaneous implants of levonorgestrel ( 1-Ng ) were obtained . No significant changes occurred in serum DHEA-S between baseline and six-month sample s. The data that 1-Ng alone and the combination of 1-Ng and ethinylestradiol did not change DHEA-S levels suggest that 1-Ng does not affect adrenal and rogen secretion . Because N , O/N and OV contain similar quantities of ethinylestradiol , these results indicate that norethindrone , but not 1-Ng , has a major suppressive effect upon adrenal and rogen secretion", "Anti and rogens or progestins with an anti and rogenic component usually have only a weak antigonadotropic activity . It is thus possible that the anti and rogenic effect on the cellular level is cancelled or at least reduced by an increased ovarian and rogen production . The aim of the four su bmi tted clinical studies of the progestin and anti and rogen dienogest alone ( 0.5 - 2 mg/day ) or of a combined regimen of ethinylestradiol ( 0.03 mg ) plus dienogest ( 2 mg ) ( EE/DNG ) was to examine the influence on the serum and rogen and SHBG concentrations as well as on the serum FSH , LH , progesterone and 17 beta-estradiol concentrations in young women . Like the progesterone derivatives , dienogest has a relatively low antigonadotropic activity . Inhibition of ovulation is mainly produced by peripheral mechanisms such as the reduction of preovulatory 17 beta-estradiol secretion . Dienogest alone has no significant effects on the serum SHBG and and rogen concentrations . Unlike this , the combination of EE plus DNG markedly increases SHBG concentrations ( to 2.1 - 3.7 fold the basal levels ) . The decrease in serum and rogens with total testosterone ( by 17 and 40 % ) , free testosterone ( by 48 and 54 % ) and dehydroepi and rosterone sulfate ( by 51 % ) corresponds to the values shown in the literature for other oral contraceptives with modern progestins . EE/DNG does not affect the serum concentrations of 5 alpha-dihydrotestosterone ( DHT ) , although the marker of the peripheral transformation from T to DHT , and rostanediol glucuronide , is distinctly reduced ( by 38 % ) . In a double-blind comparison no differences are found between EE/DNG and a regimen combining 0.02 mg of ethinylestradiol and 0.150 mg of desogestrel . Solely the SHBG concentrations , with EE/DNG , as expected , are significantly higher . In a sequential regimen , dienogest , chlormadinone acetate and desogestrel ( progestins without binding to SHBG ) enhance the inhibitory effect of ethinylestradiol sulfonate on free testosterone , whereas norethindrone acetate and levonorgestrel ( progestins with a strong binding to SHBG ) reduce this effect of the estrogen significantly . These results exclude the possibility that the very distinct anti and rogenic effect of dienogest on a cellular level is neutralised or reduced by an increased systemic supply of and rogen", "The effectiveness of a low-dose oral contraceptive ( OC ) in suppressing plasma levels of gonadotropins , ovarian , and adrenal and rogens and stimulating sex hormone-binding globulin ( SHBG ) was evaluated prospect ively in nonhirsute women . Thirty-three women ingested 35 micrograms of ethinyl estradiol and 1 mg of norethindrone beginning within day 1 to 5 of the menstrual cycle . Baseline levels of luteinizing hormone , follicle-stimulating hormone , total testosterone ( T ) , and rostenedione ( A ) , dehydroepi and rosterone sulfate ( DHEAS ) , and SHBG were obtained before ingestion of the OC and repeated after 3 , 6 and , 9 months of OC use on day 1 to 5 of the OC \" cycle \" . A significant suppression of gonadotropin levels is seen in nonhirsute women . Sex hormone binding globulin is consistently stimulated by the low-dose OC . A significant suppression of T and DHEAS is observed . No change was seen in levels of A. The demonstrated effects become evident at 3 months and are maintained at 6 and 9 months", " Twenty women using oral contraceptives and complaining of impaired sexual function were compared with twenty women without sexual problems , matched for age and oral contraceptive . Whilst the sexual behaviour differed in the two groups , the plasma testosterone , and rostenedione , oestradiol and SHBG concentrations were very similar . The total and rogen levels were low in both groups . Plasma testosterone and oestradiol concentrations were correlated with measures of sexual interest in the no‐problem group , but not in the problem group . Administration of exogenous and rostenedione to women in the problem group , using a double blind cross‐over comparison with a placebo , failed to improve their sexual function except in one case . The majority of women showed a rise in and rogen and oestradiol between day 24 of one pill cycle and day 4 of the next . The possible behavioural indications of this pattern are discussed", " Two triphasic oral contraceptives containing gestodene ( GES ) ( a new progestogen ) and levonorgestrel ( LNG ) were compared with respect to contraceptive effect , cycle control , acceptability and side effects . The serum concentrations of ingested hormones were measured together with ovarian , pituitary , and some adrenal hormones , as well as sex hormone binding globulin ( SHBG ) . The contraceptive effect and cycle control were good with both preparations , and there were only a few minor side effects . SHBG was elevated 2-fold in the LNG group and 3-fold in the GES group . The GES concentration in serum varied more than the LNG concentration , but with correction for variations in SHBG binding , less variability in actual GES and LNG concentrations was seen . Serum levels of FSH , LH , estradiol and progesterone were all depressed with both preparations . The depression was more marked in the GES group , despite lower progestogen ingestion and similar serum concentrations . Equal decreases were found in testosterone , and rostenedione and dehydroepi and rosterone sulfate ( DHEA-S ) with both preparations", "The study was performed in 14 young women . The combination oral contraceptive contained 75 μg gestodene ( GSD ) and 20 μg ethinyl estradiol ( EE2 ) per dosage unit . The volunteers received a single dose on day 21 of a treatment-free precycle ( PCd21 ) and , after a washout period of 7 days , used the preparation in a 21 d/7 d schedule for three months . Daily drug serum level profiles were taken on PCd21 and on days 1 and 21 of treatment cycles 1 and 3 . In addition , trough drug serum levels were followed every other day during treatment cycles 1 and 3 . Serum levels of GSD , EE2 , CBG , SHBG and testosterone ( T ) were determined by means of specifically developed or commercially available RIAs . Pharmacokinetic evaluation was carried out with TOPFIT and parameters were evaluated for differences with thet-test . Main target variables wereCmax , tmax and AUC for EE2 , GSD and unbound GSD on day 21 , cycle 3 vs. PCd21.EE2 pharmacokinetics were in agreement with a dose of 20 μg/unit . Single-doseCmax of 65 pg/ml and AUC of 612 pg h ml−1 increased by 40–60 % during treatment cycles as a result of accumulation . EE2 induced basal SHBG ( 102 nmol/L ) and CBG ( 42 μg/ml ) serum levels to about 220 nmol/L and 87 μg/ml , respectively , at the end of treatment cycles 1 and 3.Serum T levels dropped to 50 % of baseline levels during treatment cycles and free T concentrations were reduced by 60–70 % . GSD pharmacokinetics at the end of treatment cycles 1 and 3 were different from single-dose pharmacokinetics . Single-doseCmax of 3.5 ng/ml and AUC0–24 h of 22 ng h ml−1 increased to steady-state levels of 8–8.7 ng/ml and 90–106 ng h ml−1 , respectively . The increase in GSD levels under treatment is the result of two parallel processes , i.e. accumulation and enlargement of the specific binding compartment . This was shown by protein-binding experiments , demonstrating an increase in specific ( SHBG ) binding from 69 % to 80 % and a reduction in the free fraction of GSD by 40 % during treatment . The results of GSD and EE2 pharmacokinetics obtained in the present study confirm previous results with Femodene , when the reduction in the EE2 dose by 10 μg/d is taken into account . ResuméCette étude a été réalisée sur 14 jeunes femmes . Le contraceptif oral combiné contenait 75 μg de gestodène ( GSD ) et 20 μg d'éthinyl oestradiol ( EE2 ) par dose unitaire . Les volontaires ont reçu une dose unique au vingt et unième jour du cycle préliminaire sans traitement ( CPj21 ) et — après une période de 7 jours de sevrage — elles ont absorbé la préparation selon une posologie de 2lj/7j pendant trois mois . Les profils journaliers du taux sérique du produit ont été établis au jour CPj21 et aux jours 1 et 21 des cycles de traitement 1 et 3 . En outre , on a suivi tous les deux jours , durant les cycles 1 et 3 du traitment , les taux sériques inférieurs du produit . On a déterminé , selon des méthodes de RIA spécifiquement mises au point ou commercialement disponibles , les taux sériques de GSD , EE2 , CBG , SHBG et testostérone ( T ) . L'évaluation pharmacocinétique a été exécutée à l'aide du TOPFIT et les paramètres ont été évalués en vue de déterminer les différences avec les résultats du test-t . Les principales variables ciblées étaient lesCmax , tmax et ASC pour l'éthinyl oestradiol , GSD et GSD non lié , au jour 21 du cycle 3 par rapport au CPj21.La pharmacocinétique de l'EE2 correspondait à une dose de 20 μg/unité . LeCmax d'une dose unique de 65 pg/ml et l'ASC de 612 pg h ml−1 augmentaient de 40 à 60 % durant les cycles de traitement par suite d'accumulation . L'EE2 induisait des taux sériques de SHBG de base ( 102 nmol/l ) et de CBG ( 42 μg/ml ) d'environ 220 nmol/l et 87 μl/ml respectivement à la fin des premier et troisième cycles . Les taux sériques de T tombaient à 50 % des niveaux de base durant les cycles de traitement et les concentrations de T libre étaient réduites de 60 à 70 % . La pharmacocinétique du GSD à la fin des cycles de traitement 1 et 3 était différente de celle d'une dose unique . LesCmax d'une dose unique de 3,5 ng/ml et l'ASC0–24h de 22 ng h ml−1 augmentaient jusqu'à des niveaux stables de δ-8,7 ng/ml et 90–106 ng h ml−1 respectivement . La hausse des taux de GSD durant le traitement résulte de deux processus parallèles : accumulation et élargissement du compartiment spécifiquement liant . Ce fait est démontré par des expériences de liaison des protéines , lesquelles indiquent une liaison spécifique accrue ( SHBG ) , passant de 69 à 80 % et une réduction de la fraction libre de GSD de 40 % au cours du traitement . Les résultats de la pharmacocinétique du GSD et de l'EE2 obtenus dans la présente étude confirment ceux obtenus précédemment avec le Femodene , lorsque la réduction de 10 μg/j de la dose de EE2 est prise en compte . ResumenEste estudio se realizó con 14 mujeres jóvenes . La combinación de anticonceptivos orales contenía 75 μg de gestodén ( GDS ) y 20 μg de etinil estradiol ( EE2 ) por unidad de dosificación . Las voluntarias recibieron una sola dosis en el vigésimo primer día de un preciclo sin tratamiento ( PCd21 ) y , después de un período de interrupción de siete días — utilizaron la preparación al séptimo día de un programa de 21 días durante tres meses . Se obtuvieron perfiles diarios del nivel sérico de los fármacos en el PCd21 y en los días 1 y 21 de los ciclos del primer y tercer ciclo de tratamiento . Además , se realizó el seguimiento de los niveles séricos mínimos de los fármacos cada dos días durante el primer y tercer ciclo de tratamiento . Los niveles séricos de GSD , EE2 , CBG , SHBG y testosterona ( T ) se determinaron mediante RIA específicamente desarrollados o comercialmente disponibles . La evaluación farmacocinética se realizó con TOPFIT y se evaluaron las diferencias de los parámetros con el test-t . Las principales variables a determinar fueronCmáx , tmáx y AUC para EE2 , GSD y GSD no ligado al vigésimo primer día del tercer ciclo en comparación con PCd21.La farmacocinética de EE2 guardaba conformidad con una dosis de 20 μg/unidad . LaCmáx de dosis única de 65 pg/ml y AUC de 612 pg h ml−1 aumentó en un 40–60 % durante los ciclos de tratamiento debido a la acumulación . EE2 indujo niveles séricos de SHBG basal ( 102 nmol/l ) y CBG ( 42 μg/ml ) de aproximadamente 220 nmol/l y 87 μg/ml , respectivamente , al final del primer y tercer ciclo de tratamiento . Los niveles séricos de T se redujeron al 50 % de los niveles de línea de referencia durante los ciclos de tratamiento y las concentraciones de T libre se redujeron en un 60–70 % . La farmacocinética del GSD al concluir el primer y tercer ciclo de tratamiento fue diferente de la correspondiente a la dosis única . LaCmáx de dosis única de 3,5 ng/ml y AUC0–24h de 22 ng h ml−1 aumentó a niveles de estado estable de 8–8,7 ng/ml y 90–106 ng h ml−1 , respectivamente . El aumento de los niveles de GSD con el tratamiento se debe a dos procesos paralelos , es decir , acumulación y ampliación del compartimiento específico de ligazón . Esto se demostró mediante experimentos de ligazón de proteínas , que señalaron un aumento de la ligazón específica ( SHBG ) del 69 % al 80 % y una reducción de la fracción libre de GSD en un 40 % durante el tratamiento . Los result ados de la farmacocinética de GSD y EE2 obtenidos en el presente estudio confirman result ados anteriores con Femodene , al tenerse en cuenta la reducción de la dosis de EE2 en 10 μg/d", "The effect of seven low-dose oral contraceptive preparations on sex hormone binding globulin ( SHBG ) , cortisol binding globulin ( CBG ) , total and absolute free testosterone were investigated in groups of 10 healthy volunteers . All preparations contained about the same amount of ethinylestradiol but they differed in type and /or dose of progestagen . The progestagens studied were : levonorgestrel ( LNG ; in mono- and triphasic preparations ) , norethisterone ( NET ; in monophasic preparation ) , desogestrel ( DSG ; in mono- and biphasic preparations ) and gestodene ( GSD ; in triphasic preparation ) , all 19-nortestosterone derivatives , and the anti- and rogen cyproterone acetate ( CPA ) in a monophasic preparation . Differences observed in SHBG level , which reflect the estrogen- and rogen balance , can be attributed to the intrinsic and rogenic ( or anti- and rogenic ) properties of the progestagens , and were in agreement with the results of published receptor binding studies , performed in vitro . Based on our results the following ranking ( high to low ) can be made with respect to the and rogenicity of the preparations : monophasic LNG greater than or equal to monophasic NET = triphasic LNG greater than or equal to triphasic GSD = biphasic DSG = monophasic DSG greater than monophasic CPA . An anti-estrogenic effect of the 19-nortestosterone derived progestagens can be excluded by the effect on CBG , a marker for estrogenic activity . All preparations containing a 19-nortestosterone derived progestagen , independent of their type and dose , induce a similar rise in CBG , whereas the preparation with cyproterone acetate induced an even higher CBG level . Irrespective of the effect on total testosterone , which varies between the preparations , the absolute free testosterone level decreased to a comparable degree for all preparations . ( ABSTRACT TRUNCATED AT 250 WORDS", "In young women , low estrogen levels complicate a wide variety of diseases , including premature ovarian failure , anorexia nervosa , athletic amenorrhea , prolactinoma , hypopituitarism , and chronic kidney disease . Hypoestrogenemia may also result from therapy with GnRH agonists , glucocorticosteroids , chemotherapy , and especially aromatase inhibitors . All of these situations are associated with bone loss , because estrogen chronically suppresses bone resorption . Several mechanisms are involved : 1 ) estrogen increases osteoclast apoptosis ; 2 ) by suppressing interleukins and proinflammatory cytokine expression in bone marrow cells , estrogen decreases the number of osteoclasts ; 3 ) by inhibiting the production of receptor activator of nuclear factor-κB lig and , estrogen reduces the number and activity of osteoclasts ; and 4 ) by increasing stromal cell/osteoblast cell expression of TGFβ , estrogen inhibits osteoclast activity . Estrogen also has some positive effects on bone formation by acting as a mitogen to cells early in the osteoblast line , reducing apoptosis of osteoblasts , and increasing expression of TGFβ , bone morphogenetic proteins , and IGF-I ( 1 ) . In these pathological conditions , the cause of the bone loss is frequently multifactorial . For example , women with anorexia nervosa also have low IGF levels . Nonspecific factors such as poor diet , reduced exercise , or chronic inflammation may further increase bone resorption . Low estrogen levels are also seen in healthy young women who are using depo-medroxyprogesterone acetate ( DMPA ) for contraception . Bone loss is a side effect of this medication ( 2 ) . The bone mineral density ( BMD ) decreases at a more rapid rate during the first years of therapy and then continues to decrease at a slower rate ( 3 ) . After 5 yr , the loss is about 6 % ( 0.5 sd ) . The DMPA effects are worse in teenagers ; combined results from four prospect i ve studies found an average loss of spine BMD of 3.1 % over 2 yr in DMPA users compared with a gain of 7.2 % in untreated controls ( 4 ) . A cross-sectional study in this issue by Walsh and colleagues ( 5 ) focused on the age of starting DMPA . One group aged 18–25 started DMPA before age 20 , and another group aged 35–45 started after age 34 . Each group had matched controls . Importantly , the average use was 37 months in both groups . This avoids the confounding between age and duration of use , which is encountered in other studies . The BMD was significantly lower than controls when DMPA was started in teenagers but not when it was started after age 34 . Estrogen levels were lower in the DMPA users than the non-hormone users and were also lower in the younger women than in the older women . The authors concluded that estrogen levels mediated the effect of DMPA on bone markers because adding DMPA to a regression model reduced the correlation between markers and estrogen . These correlations were not very strong ( r = −0.17 between N-telopeptide and estradiol-treated ) , so this is a tenuous conclusion , but it is bolstered by the findings from two other studies that adding estrogen to DMPA abolishes the negative effect on the skeleton ( 6,7 ) . The age range of the older group of women is underrepresented in most of the previous studies of skeletal effects of DMPA . These results lead to several questions about basic bone biology . How are adolescent bones different from mature bones ? How does DMPA use compare to the natural state of low estrogen seen in healthy lactating women ? Is bone completely restored in these situations ? There are also important clinical questions about potential risk of fractures and the skeletal risks from other forms of contraception", "The effect of two triphasic oral contraceptives ( Triquilar [ TRQ ] and Trisiston [ TRS ] ) containing ethinyl estradiol ( EE ) and levonorgestrel ( LNG ) on various hormonal parameters was investigated in 26 women during a cross-over study . TRS consisted of 0.03 mg EE + 0.05 mg LNG ( six tablets ) , 0.04 mg EE + 0.075 mg LNG ( six tablets ) , and 0.03 mg EE + 0.15 mg LNG ( nine tablets ) , whereas TRQ was different in the second phase ( five tablets ) and third phase ( 10 tablets ) . Blood sample s were taken on days 6 , 11 , 21 , and 28 of the control and washout cycles and the third treatment cycle . Both formulations inhibited ovulation reliably and decreased the serum levels of gonadotropins , free testosterone , and dehydroepi and osterone sulfate in a time-dependent manner , whereas estradiol and testosterone were already suppressed on day 6 , indicating a direct suppressive effect on ovarian steroid synthesis . Prolactin , which rose sporadically in some women , was not significantly changed . In contrast , the levels of sex hormone binding globulin , corticosteroid binding globulin , and cortisol were significantly elevated by 100 % . During the hormone-free interval of 7 days , all parameters returned at least partly to baseline . There was no significant difference between the effects of both formulations . The results suggest the possibility of a direct inhibitory effect of contraceptive steroids on ovarian steroid synthesis", "Twenty-four healthy female volunteers with normal ovulatory cycles , aged between 20 and 34 years ( 27.5 + /- 4.3 ) , were included in a single-center , non-comparative study to investigate the effect on inhibition of ovulation of an oral contraceptive containing 20 micrograms ethinylestradiol in combination with 100 micrograms levonorgestrel . At baseline , during three treatment cycles and post-treatment , ultrasonography was used to examine the ovaries , to measure follicular size , and to measure the thickness of the endometrium . Serum levels of LH , FSH , estradiol , progesterone , total testosterone , free testosterone , SHBG , and CBG were also measured . Compared with treatment cycle 1 , an increase in residual ovarian activity ( follicle grade s 4 - 5 ) was observed in cycles 2 and 3 . Mean levels of LH , FSH , 17 beta-estradiol and progesterone remained suppressed during treatment . No escape ovulation was observed during the treatment phase of the study and there were no pregnancies . Ovulation was noted to return rapidly in the posttreatment cycle . Subjective and objective tolerance of the present regimen was noted to be good . Results indicate that the monophasic oral contraceptive containing 100 micrograms levonorgestrel combined with 20 micrograms ethinylestradiol effectively inhibits ovulation , providing adequate suppression of ovarian activity", "The effect of a triphasic oral contraceptive containing ethinylestradiol and gestodene ( EE/GSD ) on various serum hormonal parameters was compared with that of a monophasic formulation containing 35 micrograms ethinylestradiol and 250 micrograms norgestimate ( EE/NGM ) . Blood sample s were collected from 46 women on days 2 , 11 , and 21 of the preceding control cycle and of the third , sixth and twelfth treatment cycle . There was no significant difference in the influence on any hormonal parameter between both formulations . Both EE/GSD and EE/NGM caused a time-dependent suppression of serum dehydroepi and rosterone sulphate ( DHEA-S ) by 20 - 30 % ( p 5 alpha- and rostane-3 alpha , 17 beta-diol glucuronide by 50 - 60 % ( p rostenedione levels were reduced by 25 % ( p levels of total testosterone by 30 - 35 % ( p free testosterone by 60 % ( p sex hormone-binding globulin ( SHBG ) was increased by 200 - 240 % on days 11 and 21 ( p SHBG levels were reduced to a certain degree but remained elevated by 100 % as compared to the pretreatment values . The serum levels of corticosteroid-binding globulin ( CBG ) which is known to be influenced only by the estrogenic component of combination pills , increased significantly by 170 % ( p CBG levels decreased but were still elevated by 90 - 100 % as compared to the control cycle . Similarly , the serum levels of cortisol were significantly elevated by 110 - 140 % ( p < 0.01 ) during treatment with both preparations . The results demonstrate a profound suppression of and rogen levels and peripheral and rogen metabolism", "BACKGROUND This study was conducted to investigate the effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on thyroid hormones and and rogen parameters . STUDY DESIGN Thyroid and and rogen parameters were measured in 59 women treated with a monophasic combined oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest ( EE/DNG ) either conventionally ( 13 cycles with 21 days of treatment+7 days without hormones ) or according to an extended-cycle regimen ( four extended cycles with 84 days of continuous administration of EE/DNG , followed by a hormone-free interval of 7 days ) . Blood sample s were taken on Days 21 - 26 of the preceding control cycle and on Days 19 - 21 of the 3rd and 13th conventional cycle , or on Days 82 - 84 of the first and fourth extended cycle . RESULTS At both time points , the serum concentrations of thyroxine-binding globulin were elevated by about 65 % in both treatment regimens . Likewise , both groups showed an increase in total triiodothyronine ( T3 ) and total thyroxine ( T4 ) by 30 - 40 % , and no change in free T4 . Until the 12th month of conventional treatment , the level of free T3 remained unchanged but decreased slightly during the extended-cycle regimen . In both groups there was a rise of sex hormone-binding globulin by 210 - 230 % after 3 months and by 220 - 250 % after 12 months . The levels of total testosterone were reduced by about 40 % and those of free testosterone by 55 - 65 % after 3 and 12 months . CONCLUSION The results suggest that , during conventional and extended-cycle treatment with EE/DNG , a steady state in the effects on thyroid hormones and and rogen parameters was reached within 3 months and that the changes in the various hormonal parameters did not substantially differ between conventional and extended-cycle regimen", "The pharmacokinetics and and rogenic activity of Estrostep , a new oral contraceptive providing low-dose estrogen in a graduated sequence with a constant dose of progestin , were characterized in an open-label , nonr and omized study in 17 normally cycling women treated for three cycles with Estrostep . Women received 1 mg of norethindrone acetate daily combined with 20 microg of ethinyl estradiol daily for the first 5 days ( 1/20 ) , 30 microg of ethinyl estradiol daily for the next 7 days ( 1/30 ) , and 35 microg of ethinyl estradiol daily for 9 days ( 1/35 ) . No medication was given for 7 days in each cycle to allow for withdrawal bleeding . Serial blood sample s for the measurement of ethinyl estradiol and norethindrone concentrations were collected on days 5 , 12 , and 21 of the third treatment cycle for the 1/20 , 1/30 , and 1/35 dose , respectively . Sex hormone-binding globulin ( SHBG ) and free testosterone were measured at baseline , on day 1 of cycles 2 and 3 ( SHBG only ) , and on days 5 , 12 , and 21 of cycle 3 . Mean steady-state plasma ethinyl estradiol and norethindrone concentrations increased over cycle 3 . The increases in ethinyl estradiol concentrations were proportional to dose . The increases in norethindrone concentrations were related to ethinyl estradiol-dependent increases in SHBG concentrations , which were 218 % , 253 % , and 296 % of baseline values on days 5 , 12 , and 21 , respectively . Mean plasma free testosterone concentrations decreased 47 % , 60 % , and 64 % below baseline on days 5 , 12 , and 21 of cycle 3 , respectively . Graduated ethinyl estradiol doses combined with a constant norethindrone acetate dose progressively increase SHBG and decrease free testosterone , which overrides any theoretic concerns of and rogenic activity of norethindrone acetate . Although true and rogenic activity can be determined only by assessing endpoints such as acne , hirsutism , and lipids in large controlled trials , the observed changes in circulating SHBG and free testosterone concentrations indicate that Estrostep has little , if any , intrinsic and rogenic activity", "At Hospital Saint-Louis in Paris France physicians compared data on 34 women using a levonorgestrel triphasic oral contraceptive ( OC ) with data on 32 women using a norgestimate triphasic OC to examine the triphasic OCs effects on blood lipids and and rogen levels . They also compared post-OC blood lipids and and rogen levels with baseline blood lipids and and rogen levels . 47 % of all subjects smoked . After 6 cycles neither triphasic OC caused a significant difference in low density lipoprotein ( LDL ) cholesterol levels or in triglyceride levels . High density lipoprotein ( HDL ) levels in women using the norgestimate OC were significantly higher than in those using the levonorgestrel OC ( p = .001 ) . Accordingly the OCs had a significant effect on the LDL/HDL ratio . Levels of HDL subfractions ( HDL-2 and HDL-3 ) were also significantly higher in the norgestimate OC group than in the levonorgestrel OC group ( p norgestimate OC had a significant increase in apolipoproteins A-1 and 1 - 2 after 6 cycles ( 12.7 % and 15.8 % respectively ; p = .001 and .0001 respectively ) . Neither triphasic OC affected a greater increase in sex hormone binding globulin ( SHBG ) levels than did the levonorgestrel OC ( 163 % vs. 72 % ; p = .0005 ) . It reduced the free testosterone level by 40 % . The levonorgestrel OC reduced it by 30 % but neither change was significant . Neither OC had an effect on body weight or blood pressure . These findings showed a trend toward lower and rogenicity with the norgestimate OC . The norgestimate OC may be beneficial since it was linked with significant increases in all HDL subfractions and SHBG", "Objective To compare the effects on ovarian activity of two oral contraceptives containing nomegestrol acetate (NOMAC)/17β-oestradiol ( E2 ) or drospirenone (DRSP)/ethinylestradiol ( EE ) . Methods In this open-label , r and omised , six-cycle study , 32 subjects using NOMAC/E2 ( 2.5–1.5 mg ; 24/4-day regimen ) were compared to 16 subjects using DRSP/EE ( 3 mg–30 μg ; 21/7-day regimen ) . Measurements included serum oestradiol , progesterone , follicle stimulating hormone ( FSH ) and luteinising hormone ( LH ) , and ultrasonography of follicular diameter . Results No ovulations occurred during treatment . Progesterone was fully suppressed , with mean maximum values For NOMAC/E2 , mean maximum follicular diameter decreased from 19.3 mm before treatment to between 6.9 and 8.2 mm during treatment , with no subject having a follicular diameter ≥15 mm . For DRSP/EE , a decrease from 19.6 to between 7.4 and 10.8 mm was observed , with two subjects ( 12.5 % ) having a maximum follicle diameter ≥15 mm . These findings were consistent with observed FSH reductions ; full suppression of LH surges was observed in both groups . Post-treatment return of ovulation in both groups occurred on average 21 days after the last active tablet intake . Conclusions NOMAC/E2 achieves consistent ovulation inhibition , with suppressive effects on the ovaries at least similar to those of DRSP/EE", "Dehydroepi and rosterone sulfate ( DHEAS ) , which is of almost exclusive adrenal origin , is important for the and rogen status in women and prepubertal children , and DHEAS assays are used in the investigation of hyper and rogenism . There are conflicting reports concerning a diurnal variation in serum DHEAS . Although of adrenocortical origin , serum DHEAS levels are decreased by oral contraceptives ( OCs ) . DHEAS is strongly bound to serum albumin and has a very low metabolic clearance rate . The present study was performed in order to investigate whether a diurnal variation in serum DHEAS exists and , if so , whether this diurnal variation and the decreased DHEAS levels following OC use are related to alterations in adrenocortical steroids or to changes in serum albumin . Serum concentrations of DHEAS , dehydroepi and rosterone ( DHEA ) , cortisol and albumin were determined in blood sample s taken every half hour over a 24-h period in 10 healthy women before and during use of combined OCs . Significant and frequently synchronous diurnal variations in serum DHEAS and albumin were found before as well as during OC use . These variations were not synchronous with the diurnal variation in DHEA . OCs significantly decreased serum DHEAS and albumin levels . A multiple regression analysis showed changes in albumin to be the most decisive factor for the diurnal variation as and for OC-induced changes in DHEAS . Changes in serum DHEAS during the day and following OC use are related to alterations in its main binding protein , serum albumin , rather than to changes in adrenocortical steroid secretion", "CONTEXT Continuous oral contraception may better suppress the ovary and endometrium , lending itself to the treatment of other medical conditions . OBJECTIVE Our objective was to determine the effects of continuous vs. cyclical oral contraception . DESIGN This was a r and omized double-blind trial . SETTING This trial was performed at an academic medical center in Pennsylvania . PATIENTS A total of 62 healthy women with regular menses were included in the study . INTERVENTION Cyclical oral contraception ( 21-d active/7-d placebo given for six consecutive 28-d cycles ) vs. continuous ( 168-d active pill ) therapy using a monophasic pill ( 20 microg ethinyl estradiol and 1 mg norethindrone acetate ) was examined . MAIN OUTCOME MEASURES The primary outcome was vaginal bleeding , and secondary outcomes included hormonal , pelvic ultrasound , quality of life , and safety measures . RESULTS There was no statistically significant difference in the number of total bleeding days between groups , but moderate/heavy bleeding was significantly greater with the cyclical regimen [ mean 11.0 d ( sd 8.5 ) vs. continuous 5.2 d ( sd 6.8 ) ; P = 0.005 ] , with both groups decreasing over time . Endogenous serum and urinary estrogens measured over six cycles were significantly lower ( P = 0.02 and 0.04 , respectively ) in the continuous group than the cyclical group . Women in the continuous group also had a smaller ovarian volume and lead follicle size over the course of the trial by serial ultrasound examinations . The Moos Menstrual Distress Question naire showed that women on continuous therapy had less associated menstrual pain ( P = 0.01 ) and favorable improvements in behavior ( P = 0.04 ) during the premenstrual period . CONCLUSIONS Continuous oral contraception does not result in a reduction of bleeding days over a 168-d period of observation but provides greater suppression of the ovary and endometrium . These effects are associated with improved patient symptomatology" ]	411894ce-06ff-11f0-808a-c43d1ab1c353
OBJECTIVE This study aim ed at exploring available clinical instruments and methods for assessing physical oral health , and at identifying those with sufficient diagnostic performance . METHODS A systematic literature search was conducted in Embase and MEDLINE . Identified instruments and methods were critically appraised , and quality of diagnostic performance was rated by two independent review ers as A ( sufficient diagnostic performance ) , B ( either sufficient reliability or validity ) or C ( insufficient quality , or empirical results unsatisfactory and /or inconsistent ) . For all A-rated instruments and methods , an in-depth literature search was conducted to supplement and verify their effectiveness and accuracy . RESULTS A total of 141 instruments and methods were identified . Only 12 methods with sufficient diagnostic performance could be rated as A , 72 were rated as B , and 34 received a C-rating . Further 23 instruments and methods could not be rated due to lack of available information on diagnostic performance . Of all A-rated instruments , six were design ed for tooth structure , two for periodontium , one for endodontium and three for temporom and ibular joints and muscles . CONCLUSION Even though some instruments and methods exhibited good to excellent reliability and validity and can be recommended for research and clinical practice , they do not allow assessing all components of physical oral health . There is a need to identify and define st and ard instruments , and for components of physical oral health where methods with sufficient diagnostic performance are lacking , further research is required	[ "Measuring salivary flow rates among the frail elderly is a challenge . The currently used spit collection method requires levels of time and cooperation that often may exclude the frail elderly who are at high risk for salivary compromise . A measurement method that is not only valid and reliable , but also feasible and acceptable is needed for use in population studies of compromised adults . This study compared two salivary flow rate assessment methods using a suction machine against the currently accepted spit collection method in an elderly population aged 75 and older . Three methods of flow rate ( g/min ) assessment were compared at three time periods among 16 elders ( mean age 86.6 years ) . Flow rates using the 2-min open suction method compared well with the 10-min spit method ( r=0.778 ) but the 2-min closed suction method did not ( r=0.158 ) . Reliability evaluation of the open suction method and the spit method was assessed using a test/retest with a 1-week interval . Both methods demonstrated good comparable reliability ( spit method r=0.566 , P=0.01 ) ; open suction method , ( r= 0.861 , P 16 elderly subjects preferred the use of the suction machine to the spit method . These results indicate that the 2-min open suction method technique is a valid and reliable means of measuring salivary flow . The lower level of patient cooperation needed , the shorter time period required , and this preliminary report of its acceptability support the use of this method in future population studies of frail elders", "The aim of this study was to develop a valid and reproducible index of orthodontic treatment priority . After review ing the available literature , it was felt that this could be best achieved by using two separate components to record firstly the dental health and functional indications for treatment , and secondly the aesthetic impairment caused by the malocclusion . A modification of the index used by the Swedish Dental Health Board was used to record the need for orthodontic treatment on dental health and functional grounds . This index was modified by defining five grade s , with precise dividing lines between each grade . An illustrated 10-point scale was used to assess independently the aesthetic treatment need of the patients . This scale was constructed using dental photographs of 12-year-olds collected during a large multi-disciplinary survey . Six non-dental judges rated these photographs on a visual analogue scale , and at equal intervals along the judged range , representative photographs were chosen . To test the index in use , two sample population s were defined ; a group of patients referred for treatment , and a r and om sample of 11 - 12-year-old schoolchildren . Both sample s were examined using the index and satisfactory levels of intra- and inter-examiner agreement were obtained", "OBJECTIVES The aim of this r and omised clinical trial was to investigate if a laser fluorescence device is able to discriminate between sound and carious approximal sites and between enamel and dentinal lesions , as well as to find appropriate cut-off values . METHODS One hundred and seventeen sound or uncavitated carious sites in permanent molars were visually and radiographically examined , then either opened or not , after which their laser fluorescence was measured . Forty-three lesions were opened , the caries removed and the clinical ly identified caries depths were registered in addition to the radiographical scoring . Seventy-four sites were radiographically deemed sound or had enamel caries and were not opened . Here , the radiographical scorings were registered . RESULTS Taking the radiographic scoring as gold st and ard for all investigated approximal sites , sound sites ( D(0 ) , n=40 ) showed significantly lower laser fluorescence measurements than carious sites ( D(1 - 4 ) , n=77 ) ( Mann-Whitney test , P laser fluorescence values and radiographical scoring was found ( rho=+0.47 , P<0.01 ) . Analysing the 43 opened lesions with their clinical ly found lesion depths as gold st and ard , there was a fair positive correlation to the laser fluorescence values ( rho=+0.34 , P=0.03 ) and a moderately strong correlation to the radiographic scoring ( rho=+0.67 , P<0.01 ) . CONCLUSION The device may be an adjunct tool in the approximal detection of caries along with established procedures", "Today facial heat emission patterns may be rapidly obtained and quantified with the use of advanced electronic thermography units that have the promise of being a nonionizing , noninvasive , low-cost diagnostic alternative for the evaluation of temporom and ibular joint disorders . This study design measured the use of electronic thermography as a tool to select between asymptomatic ( control ) subjects and a patient group with mild to moderate temporom and ibular joint disorders . Study population s consisted of 24 asymptomatic ( control ) subjects and 20 patients with ( 1 ) either locked or unlocked temporom and ibular joints , ( 2 ) varying degrees of limitation of mouth opening , ( 3 ) mild to moderate muscle pain , and ( 4 ) mild to moderate temporom and ibular joint arthralgia . The results indicated that the control group demonstrated a high level of thermal symmetry over the temporom and ibular joint region . The patient group demonstrated a low level of thermal symmetry with a delta T value of 0.4 degrees C. The control group was selected from the patient group with 85 % sensitivity ( 17 of 20 ) , and 92 % specificity ( 22 of 24 ) , and 89 % overall accuracy ( 39 of 44 ) , when selecting among the 44 subjects used in this study . The conclusion therefore is that electronic thermography shows promise as a method of diagnosing mild to moderate temporom and ibular joint disorders", "OBJECTIVE The purpose of this study was to investigate interobserver reliability of a new technique for quantification of magnetic resonance images of temporom and ibular joint disk status . STUDY DESIGN Sixty magnetic resonance images of adolescent temporom and ibular joints were r and omly drawn for analysis . Four experienced observers traced the articular disk and osseous structures on sagittal magnetic resonance slice images . Quantitative measurements of disk length and disk displacement were recorded for each slice of 57 joints traced by each observer through use of a new quantification technique . Intraclass correlation coefficients were computed to assess interobserver agreement in the tracing of joint structures . RESULTS The calculated intraclass correlation coefficient was 0.681 for disk length and 0.830 for disk displacement . In addition , the mean variability among observers was 1.041 mm for measurement of disk length and 0.972 mm for measurement of disk displacement . CONCLUSIONS Interobserver agreement is high when the new quantification technique is used to interpret magnetic resonance images", "Clinical and radiographic diagnosis of occlusal caries is difficult . Resistance measurements in pits and fissures have shown better sensitivity compared with the more conventional methods of diagnosis . Two machines have been manufactured for this purpose : the Vanguard and the Caries Meter L. The aims of this study were to calibrate the readouts of these machines against a variable st and ard resistance box and use the Vanguard to compare readings taken in vivo and in vitro after extraction of the teeth . The diagnostic accuracy of clinical , radiographic , Vanguard and Caries Meter L diagnoses were also assessed . One hundred occlusal sites in 40 teeth of 20 patients were investigated in vivo with the Vanguard , noting clinical and radiographic appearances . The teeth were then extracted and the Vanguard readings repeated in vitro , together with Caries Meter L readings . The in vivo/in vitro comparison between Vanguard readings showed excellent reproducibility ( Cohen 's Kappa = 0.80 ) . The sensitivity and specificity for the different examination techniques at the enamel level of diagnosis were 27 % and 89 % for visual , 6 % and 100 % for radiographic , 81 % and 78 % for the Vanguard and 74 % and 74 % for the Caries Meter L. In conclusion , this study supports the renewed interest in resistance measurements as a diagnostic technique and indicates that the in vitro model used gives results comparable to those in", "PURPOSE To determine the value of magnetic resonance ( MR ) sialography for the diagnosis of sialolithiasis by comparing results prospect ively with those of ultrasonography ( US ) and digital sialography . MATERIAL S AND METHODS MR sialography was prospect ively performed with T2-weighted three-dimensional ( 3D ) constructive interference in steady-state ( CISS ) and rapid acquisition with relaxation-enhancement ( RARE ) sequences in 24 patients suspected of having sialolithiasis . Evoked salivation was used as contrast material . T1-weighted spin-echo and T2-weighted turbo spin-echo MR imaging also were performed . The results were then compared with those of US and digital sialography , with the latter as st and ard of reference . RESULTS The 3D CISS images were significantly ( P : sensitivity and specificity were 100 % and 80 % , respectively , for CISS MR sialography and 80 % and 100 % , respectively , for RARE MR imaging . The sensitivity and specificity of US were both 80 % . CONCLUSION MR sialography with evoked salivation is noninvasive and allows delineation of the subm and ibular ductal system and detection of sialoliths with accuracy that is similar to that of digital sialography and superior to that of US", "Conventional caries trials last from 24 to 36 months . This study evaluated whether the previously established difference in efficacy between 1000- and 2500-ppm-fluoride dentifrices could be detected after 12 months . Caries was assessed by clinical visual assessment ( CVA-simplified version of Dundee Selectable Threshold Method - DSTM ) , bitewing radiography , and Fiber Optic Transillumination ( FOTI ) . Changes in status for individual surfaces were classified by means of pre-prepared matrices as 0 ( unchanged ) , + 1 ( initiation or progression ) , or -1 ( regression ) and summed for each subject to yield an event score . Mean group event scores were calculated for each product . DSTM at the D1 [ enamel and dentin ] threshold showed significant inter-group differences in mean event scores ( p < 0.003 ) and D1MFS increment ( < 0.007 ) at 12 months ; these were confirmed at 24 months by traditional increment analysis ( CVA & FOTI at the D3 ( dentin only ) threshold + radiography , p < 0.03 ) . This study confirms the validity of an abbreviated trial protocol", "AIMS To examine various dimensions of reliability of the Craniom and ibular Index , a commonly used instrument for quantifying the severity of signs and symptoms of temporom and ibular disorders . METHODS Classical psychometric theory and generalizability theory were used to assess the reliability of data obtained from a calibration study of examiners participating in a multi-site clinical trial and from a r and om community sample . RESULTS The reliability of aggregate scores formed by summing individual binary scored items was high , with intraclass correlations ranging from 0.81 to 0.88 . When it was required that examiners recognize and agree upon a specific pattern of signs and symptoms exhibited by a patient , however , reliability dropped dramatically ( multivariate kappas ranged from 0.26 to 0.32 ) . A group of practicing examiners also showed limited ability to agree with the pattern of signs and symptoms identified by a \" gold st and ard \" examiner ( multivariate kappas ranging from 0.25 to 0.32 ) . Generalizability analysis failed to identify the specific sources of measurement error that played a major role in limiting reliability but demonstrated that generalizability of aggregate scores was very high . CONCLUSION Methods of classical psychometric theory and generalizability theory support the conclusion that the reliability of aggregate scores is acceptably high . Individual items assessing certain aspects of jaw mobility and joint sounds are measured with poor reliability . Reliability declines when it is defined as the ability of examiners to agree among themselves upon a specific constellation of signs and symptoms or their ability to identify correctly a \" correct \" constellation identified by an expert examiner", "BACKGROUND A study group composed of research ers from across the United States undertook a study to evaluate the sensitivity and specificity of OralCDx ( OralScan Laboratories Inc. ) , a computer-assisted method of analysis of the oral brush biopsy , in the detection of precancerous and cancerous lesions of the oral mucosa . METHODS The study group conducted a multicenter double-blind study comparing results of OralCDx analysis with those of scalpel biopsy of suspicious oral lesions , as well as using OralCDx on oral lesions that appeared benign clinical ly . RESULTS In 945 patients , OralCDx independently detected every case of histologically confirmed oral dysplasia and carcinoma ( sensitivity = 100 percent , false-negative rate = 0 percent ) . Every OralCDx \" positive \" result was subsequently confirmed by histology as dysplasia or carcinoma . The specificity for the OralCDx \" positive \" result was 100 percent , while the specificity for the OralCDx \" atypical \" results was 92.9 percent . In 4.5 percent of clinical ly benign-appearing lesions that would not have received additional testing or attention other than clinical follow-up , OralCDx uncovered dysplasia or carcinoma ( statistical sensitivity > 96 percent , P 97 percent and for the \" atypical \" result > 90 percent , P OralCDx is a highly accurate method of detecting oral precancerous and cancerous lesions . OralCDx can aid in confirming the nature of apparently benign oral lesions and , more significantly , revealing those that are precancerous and cancerous when they are not clinical ly suspected of being so . All OralCDx \" atypical \" and \" positive \" results should be referred for scalpel biopsy and histology to completely characterize the lesion . CLINICAL IMPLICATION S Given the difficulty in clinical ly differentiating premalignant and malignant lesions from benign lesions with a similar appearance , OralCDx appears to determine the significance of an oral lesion definitively and detect innocuous-appearing oral cancers at early , curable stages", "BACKGROUND Current methods of measuring saliva volume often are difficult to perform in a general dental or medical office setting . This study seeks to determine whether the Schirmer test for measuring eye dryness can be modified to measure mouth dryness . METHODS The authors performed a modified Schirmer test ( MST ) on a control group composed of 41 healthy adult volunteers and a study group composed of 10 patients who had received head and neck radiation and 10 patients who had oral chronic graft-versus-host disease ( CGVHD ) . The authors placed the strip on the floor of each subject 's mouth and took readings at one minute , two minutes and three minutes . Fourteen control subjects also spat into a container over a five-minute interval , and the authors weighed the collected saliva . RESULTS The mean reading for the control subjects at three minutes was 29.5 millimeters , while the mean reading for the test subjects was 6.9 mm ( P healthy adult volunteers and subjects who experienced profound xerostomia and hyposalivation . CLINICAL IMPLICATION S The MST as used in this preliminary study is an objective , inexpensive , easy-to-perform and well-tolerated test for measuring mouth dryness . It readily distinguishes between patients who are healthy and asymptomatic and those who experienced profound xerostomia and hyposalivation", "PURPOSE Patient salivary characteristics are being measured as part of the Northwest PRECEDENT ( Practice -based REsearch Collaborative in Evidence -based DENTistry ) study on caries risk assessment . Prior to the implementation of these salivary diagnostic tests in a practice -based cohort study , inter-examiner reliability was assessed for resting salivary pH , stimulated salivary flow rate , pH and buffering capacity . METHODS An initial evaluation of inter-examiner reliability of the 4 salivary tests was conducted among 6 dental auxiliary examiners using a convenience sample of 40 dental students . An in complete block design was used to assign sample s to examiners ( 3 examiners per sample and 20 sample s per examiner ) . Inter-examiner reliability testing was conducted on a patient population representative of the practice -based network in 4 member practice s. Two dental assistants per practice independently conducted the salivary tests on sample s provided by a r and om selection of 20 to 25 patients . A separate analysis was performed for each study . For each test , an inter-examiner reliability index was computed . RESULTS Results from two studies are reported . In the first , stimulated salivary flow rate demonstrated excellent inter-examiner reliability , and resting salivary pH showed high inter-examiner reliability , while buffering capacity and stimulated salivary pH had moderate and very low inter-examiner reliability , respectively . In the second , inter-examiner reliability was excellent for the stimulated salivary flow rate and the resting salivary pH. The inter-examiner reliability for the stimulated salivary pH was also high and the stimulated salivary buffering capacity test had moderate reliability . CONCLUSION The small variance in stimulated salivary pH and buffering capacity in dental students may have artificially made the reliability appear low in the first attempt at inter-examiner reliability testing . In the second study , all 4 tests had an accept able performance", "OBJECTIVE To provide evidence that the Dutch periodontal screening index ( DPSI ) is a valuable tool for the screening of the periodontal status and to evaluate the application of the DPSI by general practitioners in the Netherl and s. MATERIAL AND METHODS To assess the validity of the DPSI , an available data set was used consisting of 131 subjects with various degrees of periodontal breakdown in whom plaque , calculus , pocket depth , bleeding on probing and attachment loss was evaluated at all inter-proximal sites . The application of the DPSI in general practice was studied in a r and om sample of 300 practising dentists in the Netherl and s by means of a question naire . RESULTS Full-mouth inter-proximal measurements showed that 19.1 % of the subjects had > or=6 mm attachment loss at > or=2 sites . The DPSI identified 100 % of the subjects with this condition . The results of the survey question naire showed that about 75 % of the general dental practitioners were applying the DPSI , although only 15.1 % were performing this consistently when a regular check-up was performed . The mean time required for the assessment of the DPSI was 3 min . CONCLUSION The DPSI is valuable tool for the screening of the periodontal condition during general dental check-ups" ]	4118950a-06ff-11f0-808a-c43d1ab1c353
This systematic review examined the measurement properties of the 6-min walk test ( 6MWT ) , incremental shuttle walk test ( ISWT ) and endurance shuttle walk test ( ESWT ) in adults with chronic respiratory disease . Studies that report the evaluation or use of the 6MWT , ISWT or ESWT were included . We search ed electronic data bases for studies published between January 2000 and September 2013 . The 6-min walking distance ( 6MWD ) is a reliable measure ( intra-class correlation coefficients ranged from 0.82 to 0.99 in seven studies ) . There is a learning effect , with greater distance walked on the second test ( pooled mean improvement of 26 m in 13 studies ) . Reliability was similar for ISWT and ESWT , with a learning effect also evident for ISWT ( pooled mean improvement of 20 m in six studies ) . The 6MWD correlates more strongly with peak work capacity ( r=0.59 - 0.93 ) and physical activity ( r=0.40 - 0.85 ) than with respiratory function ( r=0.10 - 0.59 ) . Method ological factors affecting 6MWD include track length , encouragement , supplemental oxygen and walking aids . Supplemental oxygen also affects ISWT and ESWT performance . Responsiveness was moderate to high for all tests , with greater responsiveness to interventions that included exercise training . The findings of this review demonstrate that the 6MWT , ISWT and ESWT are robust tests of functional exercise capacity in adults with chronic respiratory disease	[ "BACKGROUND AND OBJECTIVE Cycle ergometer training is an important component of pulmonary rehabilitation for patients with COPD . However , incremental cycle tests from which individualized cycle training intensity can be prescribed may not be readily available to clinicians . The aims of the study were to ( i ) investigate the physiological and psychophysical responses to the 6-min walk test ( 6MWT ) , incremental shuttle walk test ( ISWT ) and cycle ergometer test ( CET ) ; and ( ii ) determine whether the distance walked in either the 6MWT or the ISWT could be used to estimate peak work rate on a cycle ergometer . METHODS A repeated measures study was undertaken in COPD patients in a stable condition . The 6MWT , ISWT and CET were performed in r and om order , and physiological responses , rate of perceived exertion and dyspnoea were measured . RESULTS Twenty-two patients with COPD completed the study . There was no significant difference in peak oxygen uptake between the 6MWT , ISWT and CET . The significant correlation between the 6MWD and incremental shuttle walk distance with peak watts on the CET ( r = 0.63 , P = 0.002 and r = 0.75 , P peak work rate measured on the CET and that estimated from either the 6MWT or the ISWT . CONCLUSIONS The significant relationships found between the three exercise tests , and the regression equations predicting peak work rate on the CET from the 6MWT or the ISWT , may allow for the estimation of intensity of cycle exercise training from walk tests in COPD patients", "Background In patients with COPD , both laboratory exercise tests and field walking tests are used to assess physical performance . In laboratory tests , peak exercise capacity in watts ( W peak ) and /or peak oxygen uptake ( VO2 peak ) are assessed , whereas the performance on walking tests usually is expressed as distance walked . The aim of the study was to investigate the relationship between an incremental shuttle walking test ( ISWT ) and two laboratory cycle tests in order to assess whether W peak could be estimated from an ISWT . Methods Ninety-three patients with moderate or severe COPD performed an ISWT , an incremental cycle test ( ICT ) to measure W peak and a semi-steady-state cycle test with breath-by-breath gas exchange analysis ( CPET ) to measure VO2 peak . Routine equations for conversion between cycle tests were used to estimate W peak from measured VO2 peak ( CPET ) . Conversion equation for estimation of W peak from ISWT was found by univariate regression . Results There was a significant correlation between W peak and distance walked on ISWT × body weight ( r = 0.88 , p agreement between W peak measured by ICT and estimated from ISWT was similar to the agreement between measured W peak ( ICT ) and W peak estimated from measured VO2 peak by CPET . Conclusion Peak exercise capacity measured by an incremental cycle test could be estimated from an ISWT with similar accuracy as when estimated from peak oxygen uptake in patients with COPD", "Background : Ambulatory oxygen is frequently prescribed for patients with chronic obstructive pulmonary disease ( COPD ) who have oxygen desaturation ≤88 % during exercise . The 6-min walk test ( 6MWT ) with continuous pulse oximetry monitoring is a common method to document this oxygen desaturation , but the reproducibility of this test in determining the need for ambulatory oxygen in patients with COPD is not well documented . Objective : The aim of this study was to establish the reproducibility of the 6MWT in determining the need for ambulatory oxygen prescription in stable COPD patients using the Centers for Medicare and Medicaid ( CMS ) criteria for ambulatory oxygen prescription . Methods : The study was design ed as a prospect i ve observational study in an academic health center and associated pulmonary rehabilitation program . Eighty-eight COPD patients referred to pulmonary rehabilitation underwent continuous pulse oximetry while performing st and ard 6MWT on 3 separate days . Results : Fifty-one ( 58 % ) of these patients desaturated by continuous pulse oximetry to an SpO2 ≤88 % on a least one of the 6MWTs . Only 26 patients ( 30 % ) demonstrated consistency in meeting the criteria for ambulatory oxygen set forth by the CMS on all three 6MWT with a κ statistic of 0.62 . The percent agreement between 6MWTs for ambulatory oxygen prescription was 72 % and the paired observation was 51 % . Conclusions : The 6MWT distance is simple and widely used as a consistent measure of functional capacity in patients with COPD ; however , the 6MWT oxygen saturation has only modest reproducibility in determining the need for ambulatory oxygen in stable COPD patients undergoing pulmonary rehabilitation", "Respiratory rehabilitation improves exercise capacity and quality of life in younger patients but is untried in the aged . We aim ed to : ( a ) assess repeatability of the 6-minute walk test , factors affecting it and its relation to quality of life in elderly patients with chronic obstructive airways disease ( COAD ) ; ( b ) assess compliance of such patients with an intensive respiratory rehabilitation protocol ; ( c ) pilot the assessment of the effect of respiratory rehabilitation on the 6-minute walk test in these patients . Seventeen subjects with stable , symptomatic COAD were recruited , 15 ( six men ) , 70 - 89 ( mean 76 ) years , completed the study . Mean ( st and ard deviation ) 1-second forced expiratory volume ( FEV1 ) = 49 (5)% predicted . Six-minute walk tests were repeated single-blind , 2 - 10 days apart . Quality of life was measured using Guyatt respiratory question naire . Patients underwent 12 weeks incremental respiratory rehabilitation ( x4/day step-ups , unweighed arm raises , inflating balloons ) . Baseline 6-minute walk was repeatable and was correlated with the log Guyatt dyspnoea score ( r = 0.65 , p = 0.006 ) . In multiple regression neither age nor FEV1 predicted walk distance : body mass index , maximal expiratory mouth pressure ; calorie intake . Mean ( SEM ) 6-minute walk distance after-rehabilitation was greater than baseline ( p = 0.003 ) . Elderly patients with COAD tolerate intensive respiratory rehabilitation and a controlled , blinded study is needed", "BACKGROUND The protocol used for the 6-min walk test ( 6MWT ) influences its results . The only study to examine the effect of modifying track layout performed a retrospective analysis and concluded that institutions using continuous tracks yield greater distances than those using straight tracks . Agreement between the distances measured on different tracks could not be examined . We evaluated the effect of modifying track layout on walk distance and examined the agreement and repeatability of distances measured on different tracks . METHODS In a prospect i ve , r and omized , cross-over study , 27 COPD subjects ( FEV(1 ) , 38 + /- 14 % [ mean + /- SD ] ; 15 men ) attended three separate test sessions , completing six 6MWTs . To familiarize all subjects with both tracks , the first two sessions comprised two 6MWTs on either a circular or straight track . During the final session , each subject was tested once on the straight and once on the circular track . RESULTS The distance walked on the circular track exceeded the straight track by 13 + /- 17 m ( p limit of agreement between tracks was 33 m. Coefficient of repeatability values when the test was completed on different days for the straight and circular tracks were 51 m and 65 m , respectively . CONCLUSIONS When evaluating changes in 6-min walk distance in groups of patients , track layout should be st and ardized . However , the effect of modifying track layout on an individual 's walking distance is small compared to their daily variability in walk distance . Therefore , st and ardizing track layout for any given individual may be inconsequential when evaluating the change in distances from tests performed on different days", "Background : The responsiveness of the endurance shuttle walk to functional changes following bronchodilation has recently been reported . The current literature suggests that the 6 min walking test ( 6MWT ) is less responsive to bronchodilation than the endurance shuttle walk . Aim : To compare bronchodilator-induced changes in exercise performance with the 6MWT and the endurance shuttle walk . Methods : In a r and omised , double-blind , placebo-controlled , crossover trial , 14 patients with chronic obstructive pulmonary disease ( forced expiratory volume in 1 s ( FEV1 ) 50 (8)% predicted ) completed two 6MWTs and two endurance shuttle walks , each preceded by nebulised placebo or 500 μg ipratropium bromide . Cardiorespiratory parameters were monitored during each walking test with a portable telemetric gas analyser . Quadriceps twitch force was measured by magnetic stimulation of the femoral nerve before and after each walking test . Results : The 6 min walking distance did not change significantly after bronchodilation despite a significant increase in FEV1 of 0.18 ( 0.09 ) litres ( p in FEV1 ( 0.18 ( 0.12 ) litres , p the distance walked on the endurance shuttle walk ( Δdistance ipratropium bromide – placebo = 144 ( 219 ) m , p = 0.03 ) . Quadriceps muscle fatigue was infrequent ( changes in exercise performance following bronchodilation", "We assessed the 6-min walk distance ( 6MWD ) and body weight x distance product ( 6MWw ) in healthy Brazilian subjects and compared measured 6MWD with values predicted in five reference equations developed for other population s. Anthropometry , spirometry , reported physical activity , and two walk tests in a 30-m corridor were evaluated in 134 subjects ( 73 females , 13 - 84 years ) . Mean 6MWD and 6MWw were significantly greater in males than in females ( 622 + /- 80 m , 46,322 + /- 10,539 kg.m vs 551 + /- 71 m , 36,356 + /- 8,289 kg.m , P measured 6MWD ( range , 32 + /- 71 to 137 + /- 74 m ; P 6MWD significantly correlated with age ( r = -0.39 ) , height ( r = 0.44 ) , body mass index ( r = -0.24 ) , and reported physical activity ( r = 0.25 ) . 6MWw significantly correlated with age ( r = -0.21 ) , height ( r = 0.66 ) and reported physical activity ( r = 0.25 ) . The reference equation devised for walk distance was 6MWDm = 622.461 - ( 1.846 x Ageyears ) + ( 61.503 x Gendermales = 1 ; females = 0 ) ; r2 = 0.300 . In an additional group of 85 subjects prospect ively studied , the difference between measured and the 6MWD predicted with the equation proposed here was not significant ( -3 + /- 68 m ; P = 0.938 ) . The measured 6MWD represented 99.6 + /- 11.9 % of the predicted value . We conclude that 6MWD and 6MWw variances were adequately explained by demographic and anthropometric attributes . This reference equation is probably most appropriate for evaluating the exercise capacity of Brazilian patients with chronic diseases", "Background The COPD ( chronic obstructive pulmonary disease ) assessment test ( CAT ) is a recently introduced , simple to use patient-completed quality of life instrument that contains eight questions covering the impact of symptoms in COPD . It is not known how the CAT score performs in the context of clinical pulmonary rehabilitation ( PR ) programmes or what the minimum clinical ly important difference is . Methods The introduction of the CAT score as an outcome measure was prospect ively studied by PR programmes across London . It was used alongside other measures including the St George 's Respiratory Question naire , the Chronic Respiratory Disease Question naire , the Clinical COPD Question naire , the Hospital Anxiety and Depression score , the Medical Research Council ( MRC ) dyspnoea score and a range of different walking tests . Patients completed a 5-point anchor question used to assess overall response to PR from ‘ I feel much better ’ to ‘ I feel much worse ’ . Results Data were available for 261 patients with COPD participating in seven programmes : mean ( SD ) age 69.0 ( 9.0 ) years , forced expiratory volume in 1 s ( FEV1 ) 51.1 ( 18.7 ) % predicted , MRC score 3.2 ( 1.0 ) . Mean change in CAT score after PR was 2.9 ( 5.6 ) points , improving by 3.8 ( 6.1 ) points in those scoring ‘ much better ’ ( n=162 ) , and by 1.3(4.5 ) in those who felt ‘ a little better ’ ( n=88 ) ( p=0.002 ) . Only eight individuals reported no difference after PR and three reported feeling ‘ a little worse ’ , so comparison with these smaller groups was not possible . Conclusion The CAT score is simple to implement as an outcome measure , it improves in response to PR and can distinguish categories of response", "Background — Factors that determine survival in pulmonary arterial hypertension ( PAH ) drive clinical management . A quantitative survival prediction tool has not been established for research or clinical use . Methods and Results — Data from 2716 patients with PAH enrolled consecutively in the US Registry to Evaluate Early and Long-Term PAH Disease Management ( REVEAL ) were analyzed to assess predictors of 1-year survival . We identified independent prognosticators of survival and derived a multivariable , weighted risk formula for clinical use . One-year survival from the date of enrollment was 91.0 % ( 95 % confidence interval [ CI ] , 89.9 to 92.1 ) . In a multivariable analysis with Cox proportional hazards , variables independently associated with increased mortality included pulmonary vascular resistance > 32 Wood units ( hazard ratio [ HR ] , 4.1 ; 95 % CI , 2.0 to 8.3 ) , PAH associated with portal hypertension ( HR , 3.6 ; 95 % CI , 2.4 to 5.4 ) , modified New York Heart Association/World Health Organization functional class IV ( HR , 3.1 ; 95 % CI , 2.2 to 4.4 ) , men > 60 years of age ( HR , 2.2 ; 95 % CI , 1.6 to 3.0 ) , and family history of PAH ( HR , 2.2 ; 95 % CI , 1.2 to 4.0 ) . Renal insufficiency , PAH associated with connective tissue disease , functional class III , mean right atrial pressure , resting systolic blood pressure and heart rate , 6-minute walk distance , brain natriuretic peptide , percent predicted carbon monoxide diffusing capacity , and pericardial effusion on echocardiogram all predicted mortality . Based on these multivariable analyses , a prognostic equation was derived and vali date d by bootstrapping technique . Conclusions — We identified key predictors of survival based on the patient 's most recent evaluation and formulated a contemporary prognostic equation . Use of this tool may allow the individualization and optimization of therapeutic strategies . Serial follow-up and re assessment are warranted . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00370214", "QUESTIONS Does an eight-week program of walk training improve endurance walking capacity in people with COPD compared to cycle training ? Does walk training improve peak walking capacity , cycle capacity , and quality of life compared to cycle training ? Is the endurance shuttle walk test ( ESWT ) responsive to change in walking capacity elicited by exercise training ? DESIGN R and omised trial with concealed allocation , assessor blinding , and intention-to-treat analysis . PARTICIPANTS 36 people with stable COPD recruited with four dropouts . INTERVENTION Participants were r and omised into either a walk or cycle training group . Both groups trained indoors for 30 to 45 minutes per session , three times weekly over eight weeks at Concord Hospital . Training intensities were based on baseline peak exercise tests and progressed as able . OUTCOME MEASURES The primary outcome was endurance walking capacity measured by the ESWT . Secondary outcomes included peak walking capacity , peak and endurance cycle capacity , and health-related quality of life . Measures were taken at baseline ( Week 0 ) and following training ( Week 8) . RESULTS The walk training group increased their endurance walking time by 279 seconds ( 95 % CI 70 to 483 ) more than the cycle training group . No significant differences between the groups were found for any other outcome . CONCLUSION Ground walk training increased endurance walking capacity more than cycle training and was similar to cycle training in improving peak walking capacity , peak and endurance cycle capacity and quality of life . This study provides evidence for ground walking as a mode of exercise training in pulmonary rehabilitation programs", "The effect of ambulatory oxygen use during pulmonary rehabilitation ( PR ) has not yet been clearly established , but many studies have shown benefit from oxygen acutely . Two small studies to date demonstrated no clear benefit when oxygen was used in patients who desaturated on exertion during a PR programme . One study showed the benefit of using oxygen during PR in patients who were normoxic at rest and desaturated to a minimum of 88 % on exertion . We conducted a single-blind , r and omised controlled trial comparing PR undertaken either with or without ambulatory oxygen , in those with demonstrable benefit from oxygen at baseline . Subjects from three PR services were recruited who , during baseline assessment , desaturated by more than 4 % and to less than 90 % on exertion , and walked 10 % or more further with ambulatory oxygen on endurance shuttle walk test . Patients were r and omised to either room air or oxygen via portable cylinder , titrated to optimise pulse oxygen saturation but up to a maximum flow rate of 6 L/min . All patients then completed a twice weekly , 6- to 7-week PR programme . Data were analysed as per protocol . Totally 51 patients completed the study . At the end of PR , both groups improved with PR , with patients in the oxygen group demonstrating a highly statistically significantly greater mean improvement in endurance walking distance than the controls , 490 m ( 95 % confidence interval 228–750 ; p ≤ 0.001 ) , as well as clinical ly , although not statistically , significant changes in quality of life . The use of ambulatory oxygen during a 6- to 7-week PR programme greatly improved endurance walking distance in patients who desaturated on exertion with a positive acute response to ambulatory oxygen at baseline", "Objective . The 6-minute walk test ( 6MWT ) is an important prognostic tool in various cardiovascular diseases and has been considered as a surrogate endpoint . However , conflicting results have been reported in systemic sclerosis ( SSc ) . Our objective was to evaluate the relationships of the 6-min walking distance ( 6MWD ) and organ damage in SSc . Methods . Eighty-seven consecutive patients with SSc were included and prospect ively investigated ; they underwent 6MWT in addition to conventional assessment of possible lung , heart , kidney , skin , and muscle involvement , and disease activity scoring , severity , and quality of life determination . Results . Twenty-six patients ( 30 % ) had an abnormal 6MWT and the mean 6MWD was 461.8 ± 103.0 m. When considering 6MWT as a binary variable — normal or abnormal — C-reactive protein ( CRP ) was the only independent variable associated with abnormal 6MWT . Considered as a continuous variable , the 6MWD was associated with measures of lung involvement and inflammation , with the activity and severity of disease , and also with quality of life ; nevertheless , calcinosis was the only independent factor associated in multivariate analyses with a trend for an association for CRP . Conclusion . The 6MWD relates to broad factors in SSc and these results raise doubts about the specificity of the 6MWD in this systemic disease , and its relevance to monitoring therapy", "BACKGROUND high walking frames may improve exercise capacity in young patients with chronic obstructive pulmonary disease ( COPD ) . We have assessed the effect of Zimmer , rollator and gutter frames on 6-min walking distance and on arterial oxygenation during exercise in elderly patients with COPD . METHODS 27 out- patients ( 15 men ) aged 70 - 82 ( mean 75 ) years were recruited . Exclusions comprised : COPD exacerbation or oral steroid use within 6 weeks , confusional state , participation in a pulmonary rehabilitation programme and exercise limitation by other diseases . Subjects completed 6-min walk tests unaided and with the three frames on four separate days in r and om order 30 min after nebulized salbutamol ( 5 mg ) and ipratropium ( 0.5 mg ) and were accompanied by an investigator blinded to results of all other walk tests undertaken . Oxygen saturation ( SaO2 ) was monitored by finger probe during exercise . Grouped t-tests were used to compare distances and reductions in SaO2 . RESULTS Unaided , the mean ( SEM ) 6-min walk distance was 210 ( 16 ) m and fall in oxygen saturation was 6.0 (1.1)% . Use of a rollator frame did not significantly affect either of these values . Using the Zimmer frame reduced the mean distance to 165 ( 13 ) m ( t=5.2 , P SaO2 fall similar to that recorded during the unaided walk . Using the gutter frame increased the mean distance to 234 ( 150 ) m ( t=3 . 1 , P=0.004 vs unaided walk ) and reduced the fall in SaO2 to 3.7 (0.8)% ( t=2.3 , P=0.03 vs unaided walk ) . CONCLUSIONS gutter frames improve exercise capacity and SaO2 during exercise in elderly COPD patients who remain symptomatic on optimal therapy , whereas unwheeled Zimmer frames have a deleterious effect in such patients", "RATIONALE The 6-minute-walk test ( 6MWT ) is a practical and clinical ly meaningful measure of exercise tolerance with favorable performance characteristics in various cardiac and pulmonary diseases . Performance characteristics in patients with idiopathic pulmonary fibrosis ( IPF ) have not been systematic ally evaluated . OBJECTIVES To assess the reliability , validity , and responsiveness of the 6MWT and estimate the minimal clinical ly important difference ( MCID ) in patients with IPF . METHODS The study population included all subjects completing a 6MWT in a clinical trial evaluating interferon gamma-1b ( n = 822 ) . Six-minute walk distance ( 6MWD ) and other parameters were measured at baseline and at 24-week intervals using a st and ardized protocol . Parametric and distribution-independent correlation coefficients were used to assess the strength of the relationships between 6MWD and measures of pulmonary function , dyspnea , and health-related quality of life . Both distribution-based and anchor-based methods were used to estimate the MCID . MEASUREMENTS AND MAIN RESULTS Comparison of two proximal measures of 6MWD ( mean interval , 24 d ) demonstrated good reliability ( coefficient = 0.83 ; P correlated with measures of physiologic function and health-related quality of life ; however , values were consistently and significantly lower for patients with the poorest functional status , suggesting good construct validity . Importantly , change in 6MWD was highly predictive of mortality ; a 24-week decline of greater than 50 m was associated with a fourfold increase in risk of death at 1 year ( hazard ratio , 4.27 ; 95 % confidence interval , 2.57- 7.10 ; P MCID was 24 - 45 m. CONCLUSIONS The 6MWT is a reliable , valid , and responsive measure of disease status and a valid endpoint for clinical trials in IPF", "Six-minute walk distance ( 6MWD ) is commonly used as a measure of functional exercise capacity in clinical practice and research . Regression equations to predict 6MWD in healthy individuals are available , but the equations predict distances that vary considerably for an individual . The aims of this study were to 1 ) measure 6MWDs in healthy Caucasian Australians aged 45 - 85 years ; 2 ) determine whether evidence exists for Australian-specific prediction equations for Caucasian individuals by comparing measured 6MWDs with predicted 6MWDs derived by using published regression equations ; and 3 ) develop regression equations for males and females . One hundred nine subjects ( 48 males ) completed the 6-minute walk test ( 6MWT ) . Measurements of height , leg length , weight , habitual physical activity , and peak heart rate ( HR ) achieved during the 6MWT were obtained . 6MWD ( better of two tests ) was 682 ± 73 m ( mean ± SD ) and 643 ± 70 m in the males and females , respectively ( p underestimated 6MWDs in female subjects . Gender-specific regression equations using age and anthropometric data explained 40 % and 43 % of the variance in 6MWD in males and females , respectively . Validation of the regression equations in a prospect i ve subject cohort is required", "Supplemental oxygen has acute beneficial effects on exercise performance in patients with chronic obstructive pulmonary disease ( COPD ) . The purpose of this study was to investigate whether oxygen-supplemented training enhances the effects of training while breathing room air in patients with severe COPD . A r and omized controlled trial was performed in 24 patients with severe COPD who developed hypoxaemia during incremental cycle exercise ( arterial oxygen saturation ( Sa , O2 ) All patients participated in an in-patient pulmonary rehabilitation programme of 10 weeks duration . They were assigned either to general exercise training while breathing room air ( GET/RA group : forced expiratory volume in one second ( FEV1 ) 38 % of predicted ; arterial oxygen tension ( Pa , O2 ) 10.5 kPa at rest ; Pa , O2 7.3 kPa at peak exercise ) , or to GET while breathing supplemental oxygen ( GET/O2 group : FEV1 29 % pred ; Pa , O2 10.2 kPa at rest ; Pa , O2 7.2 kPa at peak exercise ) . Sa , O2 was not allowed to fall below 90 % during the training . The effects on exercise performance while breathing air and oxygen , and on quality of life were compared . Maximum workload ( Wmax ) significantly increased in the GET/RA group ( mean ( SD ) 17 ( 15 ) W , p Six minute walking distance ( 6MWD ) , stair-climbing , weight-lifting exercise ( all while breathing room air ) and quality of life significantly increased in both groups . Acute administration of oxygen improved exercise performance before and after training . Training significantly increased Wmax , peak carbon dioxide production ( V'CO2 ) and 6MWD while breathing oxygen in both groups . Differences between groups were not significant . Pulmonary rehabilitation improved exercise performance and quality of life in both groups . Supplementation of oxygen during the training did not add to the effects of training on room air", "OBJECTIVE To determine the repeatability of the 6-minute walk test ( 6MWT ) in adolescents and adults with cystic fibrosis ( CF ) . METHODS This was a prospect i ve cross-sectional study . We included consecutive patients ages > or=15 years attending an adult CF program . The patients underwent the 6MWT , pulmonary function tests , and clinical evaluation . The second 6MWT was performed following a rest period of 60 min . RESULTS Thirty-one patients were included . The mean+/-SD age was 23.5+/-6.7 y , and the mean FEV1 was 61+/-28 % of predicted . The mean+/-SD walked distance in the first 6MWT was 583.6+/-68.6 m and in the second 6MWT was 590.0+/-72.2 m. The mean difference between the first and second 6MWT was -6.5 m , with limits of agreement between -74.9 m and 61.9 m , and the coefficient of variation was 4.3 % . The mean oxygen desaturation in the first 6MWT was 2.5+/-4.5 % , and in the second test it was 1.8+/-4.0 % . The mean difference between the first and second test was 0.6 % , and the coefficient of variation was 104 % . CONCLUSIONS Although the 6MWT distance was reproducible , the wide limits of agreement exceeded the minimum important difference for this test . These findings indicate that , in the routine evaluation of CF patients , at least two 6MWTs are required on any testing occasion to obtain a reliable estimate of the 6MWT distance", "The 6-minute walk test is used in clinical practice and clinical trials of lung diseases ; however , it is not clear whether replicate tests need to be performed to assess performance . Furthermore , little is known about the impact of walking course layout on test performance . We conducted 6-minute walks on 761 patients with severe emphysema ( mean + /- SD FEV1 % predicted = 26.3 + /- 7.2 ) who were participants in the National Emphysema Treatment Trial . Four hundred seventy participants had repeated walks on a separate day . The second test was improved by an average of 7.0 + /- 15.2 % ( 66.1 + /- 146 feet , p distance walked . Participants tested on continuous ( circular or oval ) courses had a 92.2-foot longer walking distance than those tested on straight ( out and back ) courses . Course length had no significant effect on walking distance . The training effect found in these patients with severe emphysema is less than in previous reports of patients with chronic obstructive pulmonary disease . Furthermore , the layout of the track may influence the 6-minute walk performance", "The six-minute walk test ( 6MWT ) has been broadly used in clinical setting s. Several reference equations for prediction of the total distance walked during the test ( 6MWD ) are available in literature . The present review aim ed to critically discuss studies , published in Portuguese and English ( LILACS , SCIELO , MEDLINE , PUBMED ) , which evaluated normal values and created reference equations for predicting 6MWD in healthy subjects , comparing them with the results that were recently obtained in Brazilian individuals . Age , sex , weight , height and body mass index were the main demographic and anthropometric features more often correlated with 6MWD . The equations derived from these characteristics were able to explain between 25 and 66 % of the total variability in the 6MWD . Unfortunately , the foreign equations were not applicable to the Brazilian population . Even when the 6MWT was performed following strict st and ardization , the difference in 6MWT performance between foreign and Brazilian individuals remains , indicating the necessity of providing specific reference equations for each population and /or ethnic group . Accordingly , these equations developed in Brazil are probably the most appropriate for interpreting 6MWT performance in Brazilian patients with chronic diseases affecting the exercise capacity . Future studies are necessary with larger sample sizes ( e.g. multicentric ones ) and r and omized design for the reference values of the 6MWD to be considered reliable", "UNLABELLED The 6-min walk ( 6MW ) test is commonly used to assess exercise capacity in patients with COPD and to track functional change result ing from disease progression or therapeutic intervention . Not surprisingly , distance covered has been the preferred outcome for this test . However , distance walked does not account for differences in body weight that are known to influence exercise capacity . OBJECTIVE The aim of this study was to evaluate the 6-min distance x body weight product ( 6MWORK ) as an improved outcome measure with a solid physiologic foundation . PATIENTS AND METHODS One hundred twenty-four men and women with moderate-to-severe COPD volunteered and completed the testing sequence , which included pulmonary function , a peak effort ramp cardiopulmonary exercise study with gas exchange , and the 6MW . Means and SD were generated for the variables of interest . Differences were analyzed using analysis of variance techniques . Correlation coefficients and receiver operating characteristic ( ROC ) curves were calculated for the 6-min walk distance ( 6MWD ) and 6MWORK with indexes of pulmonary function , work performance , and Borg scores for dyspnea and effort . RESULTS Men and women presented with a significant smoking history that also differed by gender ( 48 vs 66 pack-years , respectively ; p mean ( + /- SD ) FEV(1 ) values were 45 + /- 12.6 % and 48 + /- 12.1 % , respectively ( not significant ) , while the diffusing capacity of the lung for carbon monoxide ( DLCO ) was 14.7 + /- 6.1 vs 10.3 + /- 3.9 mL/min/mm Hg , respectively ( p 6MWD averaged 416.8 + /- 79.0 m for men and 367.8 + /- 78.6 m for women , and these differences were significant ( p 0.05 ) , respectively . 6MWORK averaged 35,370 + /- 9,482 kg/m and 25,643 + /- 9,080 kg/m ( p higher correlation coefficients than did 6MWD when correlated with DLCO , lung diffusion for alveolar ventilation , FEV(1 ) , FEV(1)/FVC ratio , watts , peak oxygen uptake , peak minute ventilation , and peak tidal volume . The ROC curve demonstrated that 6MWORK had a significantly larger calculated area under the curve ( p 6MWD when differentiating an objective ly selected definition of low work capacity vs high work capacity ( bike ergometry work , 55 W , respectively ) . CONCLUSIONS We conclude that work calculated as the product of distance x body weight is an improved outcome measure for the 6MW . 6MWORK can be used whenever the 6MW is required to estimate a patient 's functional capacity . This measure is also a common measure , which can be converted to indexes of caloric expenditure for direct cross-modality comparisons", "PURPOSE This study assessed the effect of a wheeled walking aid on disability , oxygenation , and breathlessness in patients with severe disability secondary to chronic irreversible airflow limitation . METHODS Eleven subjects with chronic irreversible airflow limitation , mean forced expired volume in 1 second ( FEV1 ) 0.71 L + /- .33 L , were studied . Subjects performed four 6-minute walk tests , two on each of two study days , twice unaided and twice with the assistance of a wheeled walking aid . A r and omized cross-over design was used . All subjects were oriented to 6-minute walk tests , use of bronchodilators was controlled , and st and ard encouragement was given during each walk test . Outcome measures were the distance walked in 6 minutes , change in oxyhemoglobin saturation during the walk , and breathlessness using a modified Borg Scale . RESULTS The use of a wheeled walker result ed in a significant increase in 6-minute walking distance , a significant reduction in hypoxemia with walking and a significant reduction in breathlessness during the walk test . CONCLUSIONS The use of a wheeled walker result ed in significant decreases in disability , hypoxemia , and breathlessness during a 6-minute walk test . By reducing disability and breathlessness , a wheeled walker may improve quality of life in individuals with severe impairment in lung function", "BACKGROUND AND OBJECTIVE Pulmonary rehabilitation guidelines recommend cycle ergometry training at an intensity that exceeds 60 % of peak power ( P(peak ) ) with the aim of achieving a physiologic response . However , many clinicians do not have access to an incremental cycle ergometry test ( ICET ) to allow prescription of training intensity . No studies have investigated whether the 6MWT can be used to estimate the P(peak ) achieved during an ICET in subjects with IPF or in Asian subjects with COPD . METHODS A total of 90 Japanese subjects ( IPF n = 45 , COPD n = 45 ) undertook a 6MWT and a symptom-limited ICET in r and om order . Anthropometry , quadriceps strength and lung function were measured . RESULTS Exercise tests were prematurely terminated in 10 subjects with IPF due to profound oxygen desaturation ( SpO(2 ) higher peak heart rates , dyspnea and leg fatigue in both subject cohorts ( all P magnitude of oxygen desaturation was greater during the 6MWT ( P P(peak ) ( r = 0.80 , P P(peak ) included 6MWD and FVC % pred ( R(2 ) = 0.70 ) . In the COPD subjects , 6MWD alone accounted for 64 % of the variance in P(peak ) and the inclusion of other variables did not increase R(2 ) . CONCLUSIONS P(peak ) can be estimated from the 6MWT in Japanese subjects with IPF and COPD . This may allow individualized prescription of the intensity for cycle-based training based on the 6MWT", "Objective This study determined the intensity of walking exercise prescribed from 70 % of peak speed achieved during the incremental shuttle walk test ( ISWT ) in people with chronic obstructive pulmonary disease and whether a steady-state response was achieved when exercising at this intensity . Design Each participant performed lung function tests , an incremental cycle test , two ISWTs , and a 10-min continuous walking exercise at 70 % peak ISWT speed . Oxygen consumption ( V˙O2 ) was collected using a portable system ( Cosmed K4b2 , Rome , Italy ) . The V˙O2 from the 10-min walking exercise was compared with V˙O2peak from the better ISWT as a measure of walking exercise intensity . Results Thirty-four participants completed the study . The mean intensity achieved during the 10-min walking exercise was 76 % ( 11 % ) V˙O2peak . Steady-state V˙O2 was achieved by minute 5 in the 10-min walking exercise . Conclusions Prescription of walking exercise at 70 % of the peak ISWT speed provided an intensity appropriate for achieving physiologic training responses", "Patients with pulmonary arterial hypertension ( PAH ) exhibit a limited increase in stroke volume on exercise , and the heart rate ( HR ) increases may reflect the main mechanism that allows cardiac output to increase . The current prospect i ve study documented the contribution of HR to the 6-min walking distance ( 6MWD ) in idiopathic ( IPAH ) and nonidiopathic PAH . Eighty-three patients ( 46 IPAH and 37 nonidiopathic PAH ) underwent haemodynamic evaluation and a 6MWD test . Chronotropic response ( peak walking HR minus resting HR ) and peripheral oxygen saturation were monitored . Fifty-seven patients were also assessed after 5±2 months of treatment ( bosentan n = 38 , epoprostenol n = 14 , bosentan-epoprostenol n = 3 , iloprost n = 2 ) . Before treatment , the 6MWD was related to numerous demographic , haemodynamic and walking test characteristics . Stepwise regression analysis indicated that the only factors significantly associated with the 6MWD were stroke volume and chronotropic response in both IPAH and nonidiopathic PAH patients . Following treatment , changes in 6MWD were significantly related to changes in chronotropic response in both IPAH and nonidiopathic PAH . In conclusion , baseline stroke volume and chronotropic response were independently associated with the 6-min walking distance in pulmonary arterial hypertension . The lack of chronotropic response may reflect the loss in normal physiological reserve in more unwell patients", "OBJECTIVE Surgery remains the treatment of choice in patients with potentially resectable lung carcinoma . Both the British Thoracic Society and American Chest Physician guidelines for the selection of patients with lung cancer surgery suggest the use of a shuttle walk test to predict outcome in patients with borderline lung function . The guidelines suggest that if the patient is unable to walk 250 m during a shuttle walk test , they are high risk for surgery . However , there is no published evidence to support this recommendation . Therefore , we undertook a prospect i ve study to examine the relationship between shuttle walk test and surgical outcome in 139 patients undergoing assessment for possible lung cancer surgery . METHODS The shuttle walk test was performed in 139 potentially resectable patients , recruited over a 2 year period , prior to surgery . One hundred and eleven patients underwent surgery . Outcome of surgery , including duration of hospital stay , complication and mortality rates was recorded . Student 's t-test was used to compare the shuttle walk distance in patients with good and poor outcome from surgery . RESULTS Mean age of patients undergoing surgery was 69 years ( 42 - 85 ) . Mean shuttle walk distance was 395 m ( 145 - 780 ) , with a mean oxygen desaturation of 4 % ( 0 - 14 ) during the test . Sixty nine patients had a good surgical outcome and 34 had a poor outcome . The shuttle walk distance was not statistically different in the two outcome groups . CONCLUSION Shuttle walk distance should not be used to predict poor surgical outcome in lung cancer patients , contrary to current recommendations . It is therefore advisable to perform a formal cardiopulmonary exercise test if at all possible . The usefulness of a shuttle walk test might be improved . It could be compared to a predicted value , as for a formal cardiopulmonary exercise test", "Walking tests , frequently used to document effects of treatment on exercise capacity , have never been st and ardised . We studied the effects of encouragement on walking test performance in a r and omised study that controlled for the nature of the underlying disease , time of day , and order effects . We r and omised 43 patients with chronic airflow limitation or chronic heart failure or both to receive or not receive encouragement as they performed serial two and six minute walks every fortnight for 10 weeks . Simple encouragement improved performance ( p less than 0.02 for the six minute walk ) , and the magnitude of the effect was similar to that reported for patients in studies purporting to show beneficial effects of therapeutic manoeuvres . Age and test repetition also affected performance . These results demonstrate the need for careful st and ardisation of the performance of walking tests , and suggest caution in interpreting studies in which st and ardisation is not a major feature of the study design", "Background Sarcoidosis is a chronic disease with different phenotypic manifestations . Health-related quality of life is an important aspect in sarcoidosis , yet difficult to measure . The objective of this study was to identify clinical markers predictive of poor quality of life in sarcoidosis patients that can be followed over time and targeted for intervention . Methods We assessed the quality of life of 162 patients with confirmed sarcoidosis in a prospect i ve , cross-sectional study using the Sarcoidosis Health Question naire ( SHQ ) and Short Form-36 Health Survey ( SF-36 ) . We evaluated the validity of these question naires and sought to identify variables that would best explain the performance scores of the patients . Results On multivariate regression analyses , the very best composite model to predict total scores from both surveys was a model containing the distance-saturation product and Borg Dyspnea Scale score at the end of a 6-min walk test . This model could better predict SF-36 scores ( R2 = 0.33 ) than SHQ scores ( R2 = 0.24 ) . Substitution of distanced walked in 6 min for the distance-saturation product in this model result ed in a lesser ability to predict both scores ( R2 = 0.26 for SF-36 ; R2 = 0.22 for SHQ ) . Conclusions Both the SHQ and SF-36 surveys are valuable tools in the assessment of health-related quality of life in sarcoidosis patients . The best model to predict quality of life among these patients , as determined by regression analyses , included the distance-saturation product and Borg score after the 6-min walk test . Both variables represent easily obtainable clinical parameters that can be followed over time and targeted for intervention", "The 6-min walking test ( 6MWT ) is frequently used to assess functional capacity in chronic cardiopulmonary disorders because of its simplicity . The study examines the physiological responses during encouraged 6MWT in patients with chronic obstructive pulmonary disease . Pulmonary oxygen ( O2 ) uptake ( V′O2 ) was measured in 20 male patients ( age 66±6 yrs , forced expiratory volume in one second 45±14 % predicted ) during 6MWT and incremental cycling , in r and om order . O2 tension in arterial blood , carbon dioxide tension in arterial blood and arterial lactate concentration ( [La]art ) were obtained in the last 10 patients . During the 6MWT , V′O2 showed a plateau after the 3rd min ( 1.39±0.28 , 1.42±0.31 , and 1.40±0.30 L·min−1 , 4th , 5th and 6th min , respectively ) , and minute ventilation ( V′E ) ( 42±8 L·min−1 ) was 91 % maximal voluntary ventilation . No differences were shown between 6MWT ( 6th min ) and peak cycling exercise in V′O2 ( 1.40±0.30 versus 1.41±0.28 L·min−1 , respectively ) , cardiac frequency ( 126±13 versus 130±12 beats·min−1 ) , or arterial respiratory blood gases . The two tests were significantly different in V′E ( 42±8 versus 47±8 L·min−1 , 6MWT versus cycling , respectively ) , carbon dioxide production ( 1.30±0.31 versus 1.45±0.18 L·min−1 ) and [La]art ( 2.9±1.99 versus 5.9±1.51 M ) . The study demonstrates that an encouraged 6-min walking test generates a high but sustainable oxygen uptake . Since the oxygen uptake plateau reflects the integrated response of the system , it may explain the high prognostic value of the 6-min walking test ", "Background Measurements of Energy Expenditure ( EE ) at rest ( REE ) and during physical activities are increasing in interest in chronic patients . In this study we aim ed at evaluating the validity/reliability of the SenseWear ® Armb and ( SWA ) device in terms of REE and EE during assisted walking in Chronic Respiratory Failure ( CRF ) patients receiving long-term oxygen therapy ( LTOT ) . Methodology /Principal Findings In a two-phase prospect i ve protocol we studied 40 severe patients and 35 age-matched healthy controls . In phase-1 we determined the validity and repeatability of REE measured by SWA ( REEa ) in comparison with st and ard calorimetry ( REEc ) . In phase-2 we then assessed EE and Metabolic Equivalents-METs by SWA during the 6-minute walking test while breathing oxygen in both assisted ( Aid ) or unassisted ( No-Aid ) modalities . When compared with REEc , REEa was slightly lower in patients ( 1351±169 vs 1413±194 kcal/day respectively , p COPD patients with CRF patients reported a significant gain with Aid as compared with No-Aid modality in terms of meters walked , perceived symptoms and EE . Conclusions / Significance SWA provides a feasible and valid method to assess the energy expenditure in CRF patients on LTOT , and it shows that aided walking results in a substantial energy saving in this population", "The purpose of this study was to investigate the relationship between performance on the shuttle walking test and maximal oxygen uptake ( VO2max ) during a conventional treadmill test in patients with chronic airflow limitation . Two different techniques were used to measure oxygen consumption , i.e. conventional Douglas bag techniques ( treadmill test ) and a portable oxygen consumption meter ( shuttle test ) . Initially , 19 patients performed a shuttle walking test ( after one practice walk ) and a maximal treadmill walking test , in a r and omized , balanced design . Subsequently , 10 patients , ( after one practice ) completed an unencumbered shuttle walking test and one supporting the portable oxygen consumption meter , in r and om order . The results of the first experiment revealed a strong relationship between performance during the shuttle walking test and VO2max during the treadmill walking test ( r = 0.88 ) . The results of the second experiment consistently demonstrated an incremental increase in oxygen consumption and ventilation in response to the increasing intensity of the shuttle walking test . Again , a strong relationship between VO2max and performance on the shuttle test was demonstrated ( r = 0.81 ) . We concluded that the shuttle walking test is a valid field exercise test of functional capacity . Performance on the test relates strongly to VO2max , the traditional indicator of cardiorespiratory capacity", "Exercise impairment as measured by the 6-min walk distance ( 6MWD ) test afflicts many patients with chronic obstructive pulmonary disease ( COPD ) and is known to predict mortality . Reference equations for the 6MWD in adults have been published but not yet vali date d. The present authors prospect ively followed 1,379 COPD patients for 55±30 months and tested the predictive value of the baseline 6MWD in metres , the 6MWD work ( kg·m−1 ) and as a percentage of predicted values the 6MWD in meters according to two reference equations . All-cause mortality was the validating outcome . The best threshold values were identified for each of the tests using receiver operating characteristic ( ROC ) curves . The threshold values obtained were : 350 m for the 6MWD , 25,000 kg·m−1 for the 6MWD work , and 67 and 54 % predicted for the two reference equations . All modalities of the testing were similar at predicting COPD mortality and correlated well with the 6MWD test . In conclusion , all modalities of testing predict mortality in chronic obstructive pulmonary disease equally well . In the 6-min walk distance test , a value with increased mortality and should be regarded as abnormal", "Our aim was to determine the minimal important difference ( MID ) for 6-min walk distance ( 6MWD ) and maximal cycle exercise capacity ( MCEC ) in patients with severe chronic obstructive pulmonary disease ( COPD ) . 1,218 patients enrolled in the National Emphysema Treatment Trial completed exercise tests before and after 4–6 weeks of pre-trial rehabilitation , and 6 months after r and omisation to surgery or medical care . The St George 's Respiratory Question naire ( domain and total scores ) and University of California San Diego Shortness of Breath Question naire ( total score ) served as anchors for anchor-based MID estimates . In order to calculate distribution-based estimates , we used the st and ard error of measurement , Cohen 's effect size and the empirical rule effect size . Anchor-based estimates for the 6MWD were 18.9 m ( 95 % CI 18.1–20.1 m ) , 24.2 m ( 95 % CI 23.4–25.4 m ) , 24.6 m ( 95 % CI 23.4–25.7 m ) and 26.4 m ( 95 % CI 25.4–27.4 m ) , which were similar to distribution-based MID estimates of 25.7 , 26.8 and 30.6 m. For MCEC , anchor-based estimates for the MID were 2.2 W ( 95 % CI 2.0–2.4 W ) , 3.2 W ( 95 % CI 3.0–3.4 W ) , 3.2 W ( 95 % CI 3.0–3.4 W ) and 3.3 W ( 95 % CI 3.0–3.5 W ) , while distribution-based estimates were 5.3 and 5.5 W. We suggest a MID of 26±2 m for 6MWD and 4±1 W for MCEC for patients with severe COPD", "Few studies have shown that the endurance shuttle walking test ( ESWT ) is responsive to treatment in patients with chronic obstructive pulmonary disease ( COPD ) . This exercise test needs to be further investigated because of its relevance for activity of daily living . The aim of the present study was to evaluate , in patients with COPD , the responsiveness of the ESWT in detecting improvement in walking performance after a single dose of salmeterol . In a r and omised , double-blind , placebo-controlled crossover trial , 20 patients with COPD performed two ESWT at 80 % of peak capacity 2.5 h after inhaling either a placebo or 50 µg of salmeterol . Cardiorespiratory parameters were monitored during each walking test . Inspiratory capacities and Borg ratings for dyspnoea were obtained every other minute throughout the tests . Compared with placebo , salmeterol produced a significant change in lung function and a significant improvement in walking performance ( mean±sd difference in time : 117±20 s ; difference in distance : 160±277 m ) . At isotime ( the latest exercise time that was reached on both ESWT ) , a significant reduction in dyspnoea was observed after bronchodilation . Bronchodilation with salmeterol reduced dyspnoea during walking and improved walking capacity in patients with chronic obstructive pulmonary disease . These findings provide further support for the use of the endurance shuttle walking test as an evaluative tool in chronic obstructive pulmonary disease", "PURPOSE To investigate whether the acute benefits of rollator use are consistent over time in individuals with moderate to severe chronic obstructive pulmonary disease . METHODS Thirty-one stable subjects with chronic obstructive pulmonary disease ( 13 men , 18 women ) , aged 68 + /- 8 years , with a forced expiratory volume in 1 second of 0.7 + /- 0.2 L ( 33 % + /- 12 % predicted ) and a baseline 6-minute walk ( 6MW ) of 261 + /- 68 m , were recruited from a respiratory clinic after completion of a pulmonary rehabilitation program . Two 6MWs were performed at baseline , 4 weeks , and 8 weeks , one walking unaided and the other walking with the assistance of a rollator . The test order was r and omly chosen at baseline , and the same test order was used at each time point . The primary outcome measures were distance walked in 6 minutes ( meters ) , perceived dyspnea using a modified Borg scale , and number of rests taken . RESULTS Subjects achieved higher 6MW distances during assisted compared with unassisted walking at baseline ( 292 + /- 67 vs 263 + /- 67 m ) , 4 weeks ( 296 + /- 62 vs 275 + /- 63 m ) , and 8 weeks ( 283 + /- 65 vs 259 + /- 68 m ) ( P = .013 ) , with no time effect ( P = .5 ) . In addition , use of a rollator result ed in a significant improvement in dyspnea ( P = .004 ) at baseline , 4 weeks , and 8 weeks , with no time effect ( P = .7 ) . The use of a rollator also reduced the number of rests taken during the 6MW ( P Rollator use result ed in improvements in performance in the 6MW , which were consistent over time among individuals with moderate to severe chronic obstructive pulmonary disease who walk less than 375 m during an unaided 6MW", "The effect of oxygen on breathlessness and exercise tolerance was examined in \" pink and puffing \" patients with fixed airways obstruction . When breathing oxygen , patients were less breathless and walked further . This was true whether the cylinder was carried by the patient or by an assistant . It was not possible to identify those patients who would benefit most . The best method of assessing improvement was by comparing breathlessness on a st and ardised progressive exercise test on a treadmill . Four patients had a greater than 30 % reduction in breathlessness on submaximum exercise when breathing oxygen . Breathing oxygen for five or fifteen minutes before exercise but not during exercise ( predose ) result ed in a similar improvement in exercise tolerance . For short periods of exercise predosing with oxygen provides a convenient alternative to continuous oxygen . For longer periods of exercise the benefits of portable oxygen in selected patients have been previously underestimated", "RATIONALE There is no consensus regarding which exercise test to use to evaluate the functional impact of bronchodilators in patients with chronic obstructive pulmonary disease . OBJECTIVE AND METHODS Bronchodilator-induced changes in endurance time were evaluated during cycling and walking in 17 patients with chronic obstructive pulmonary disease who completed two cycle endurance tests and two endurance shuttle walks at 80 % of peak capacity . Each endurance test was preceded by the nebulization of a placebo or 500 microg of ipratropium bromide using a r and omized , double-blind , crossover design . Quadriceps twitch force was measured with magnetic stimulation of the femoral nerve before and after each endurance test . RESULTS Cycling endurance time did not improve significantly after bronchodilation despite a significant increase in FEV1 ( delta endurance time ipratropium bromide - placebo : 51 + /- 255 s , p = 0.42 ) . A similar change in FEV1 was associated with a significant improvement in walking endurance time ( delta endurance time ipratropium bromide - placebo : 164 + /- 177 s , p quadriceps twitch force was observed after cycling , whereas no significant change was seen after walking . CONCLUSION The endurance shuttle walk is a sensitive test to detect changes in exercise tolerance after bronchodilation . Differences in the occurrence of quadriceps muscle fatigue may explain , in part , the different responsiveness to change between cycling and walking", "BACKGROUND Exercise tolerance is an important clinical aspect of chronic obstructive pulmonary disease that can be easily and reliably measured with the 6-minute walking test ( 6MWT ) . To improve the utility of the 6MWT for patient and health care system management , the interpretation of the functional status measure in relation to death and hospitalization should be eluci date d. METHODS Three-year , prospect i ve , multicenter observational study to evaluate the predictive power of 6MWD for death or exacerbation-related hospitalization and to evaluate the factors that help determine 6MWD . RESULTS We measured 6MWD at baseline and annually in 2110 patients with clinical ly stable Global Initiative for Obstructive Lung Disease ( GOLD ) stage II-IV COPD and recorded exacerbation-related hospitalizations and all-cause mortality . During the study , 200 patients died and 650 were hospitalized . Using receiver operating characteristics , the best predictive thresholds of the 6MWD were 334 m for increased risk of death and 357 m for exacerbation-related hospitalization ( area under the curve 0.67 and 0.60 respectively ) ; however , the discriminatory thresholds , especially for mortality , were influenced by age . The mean ( SE ) 6MWD declined by 1.6 ( 1.2 ) m per year in GOLD II , 9.8 ( 1.3 ) m per year in GOLD III , and 8.5 ( 2.4 ) m per year in GOLD IV . CONCLUSION The 6MWD provides prognostic information that may be useful for identifying high-risk patients with COPD", "STUDY OBJECTIVE To assess the relationship of distance ambulated during the 6-min walk test ( 6'WT ) to maximal oxygen consumption ( VO2 max ) . DESIGN Multivariate analysis of patient characteristics to VO2 max . SETTING Pre-lung transplant evaluation . PATIENTS 60 patients ( 22 men , 38 women ; mean age , 44 years ) with end-stage lung disease ( mean FEV1 and forced vital capacity of 0.97 and 1.93 , respectively ) . MEASUREMENTS AND RESULTS The 6'WT was performed on a level hallway surface , and VO2 max was obtained during maximal cycle ergometry exercise testing with respiratory gas analysis . Multivariate analysis of patient characteristics ( age , sex , weight , FEV1 , FVC , diffusing capacity for carbon monoxide ( DCO ) , 6'WT distance ambulated , number of rests per 6'WT , and the maximal heart rate , blood pressure , rate-pressure product , respiratory rate , oxygen saturation , rating of perceived exertion , and amount of supplemental oxygen used during the 6'WT ) was performed on two groups of 30 patients each ( group A or B ) who were r and omly assigned to either group by a process of r and om selection using a computer-generated r and om numbers program . Distance ambulated was the strongest independent predictor of VO2 max ( r = 0.73 ; p distance ambulated during the 6'WT to VO2 max , the prediction equation obtained from the multivariate analysis of group A , VO2 max = 0.006 x distance ( feet ) + 3.38 , was used to estimate the VO2 max of the group B patients . No significant difference was observed between the estimated ( x + /- SD = 8.9 + /- 2.4 mL/kg/min ) and observed ( x + /- SD = 9.4 + /- 3.8 mL/kg/min ) VO2 max ( mean difference , 0.5 mL/kg/min ; SD of the difference = 2.88 ) . CONCLUSIONS The distance ambulated during a 6'WT can predict VO2 max in patients with end-stage lung disease . The addition of several patient characteristics can increase the ability to predict VO2 max and account for more of the variability . Such information is valuable when assessing patient response to therapeutic intervention if respiratory gas analysis is unavailable or impractical", "STUDY OBJECTIVE We analyzed the effects of the use of a rollator on walking distance and physiologic variables : pulmonary gas exchange , heart rate , minute ventilation ( Ve ) , oxygen saturation , and symptoms during the 6-min walk test ( 6MWT ) in patients with COPD . SETTING Outpatient clinic at university hospital . PATIENTS Fourteen patients with COPD in stable clinical condition . One patient had mild COPD , five patients had moderate COPD , six patients had severe COPD , and two patients had very severe COPD . INTERVENTIONS Two 6MWTs were performed with a portable metabolic system ( VmaxST 1.0 ; Viasys Healthcare ; MEDA ; Aartselaar , Belgium ) with a rollator and without a rollator , in r and om order . In addition , maximal voluntary ventilation ( MVV ) was measured with and without a rollator , r and omly . RESULTS The median 6MWT distance increased significantly with a rollator : 416 m without a rollator ( interquartile range [ IQR ] , 396 to 435 m ) , vs 462 m with a rollator ( IQR , 424 to 477 m ) [ p = 0.04 ] . Significant increases were also seen in oxygen uptake ( 0.04 L/min [ IQR , - 0.002 to 0.09 L/min ] ) ; tidal volume ( 0.06 L/min [ IQR , - 0.001 to 0.11 L/min ] ) ; and Ve ( 0.95 L/min [ IQR , - 0.67 to 7.1 L/min ] ) , recorded in the last minute of the 6MWT ; as well as in MVV ( 3 L/min [ IQR , 0 to 12 L/min ] ) [ p Borg dyspnea scores tended to be lower with a rollator : 6 ( IQR , 4 to 7 ) without a rollator , vs 5 ( IQR , 4 to 7 ) with a rollator ( p = 0.10 ) . The variation in the 6MWT was explained by individual changes in walking efficiency ( partial R(2 ) = 0.31 ) and changes in Ve ( partial R(2 ) = 0.36 ) [ p model rollator improves walking distance of patients with COPD through an increased ventilatory capacity and /or better walking efficiency", "Background : There is a concern that comorbidity or frailty in older people could limit the usefulness of currently available exercise tests for chronic lung disease . This study evaluated the feasibility and reproducibility of the incremental shuttle walking test ( SWT ) in people aged 70 years or over , compared exercise tolerance with other disability markers , and assessed whether the SWT is responsive to change after bronchodilators . Methods : Fifty elderly patients with chronic airflow limitation ( CAL ) and 32 controls without airflow limitation attempted the SWT before and after combined nebulised salbutamol/ipratropium bromide . Subjects also completed the Nottingham Extended Activities of Daily Living index ( NEADL ) and the London H and icap score ( LHS ) . Results : Forty four subjects with CAL ( 88 % ) and 29 controls ( 84 % ) completed the SWT , including many with co-morbidities . Two week repeatability was good and the SWT was strongly associated with EADL ( r=0.51 , p LHS ( r=0.43 , p forced expiratory volume in 1 second ( FEV1 ) ( r=0.31 , p=0.05 ) . Subjects with CAL walked a mean distance of 177.7 m compared with 243.3 m in controls ( p distance walked increased in the CAL group by 13.2 % ( p=0.009 ) . Conclusion : The SWT is a feasible and reproducible measure of exercise tolerance in elderly people with and without airflow obstruction and correlates with other markers of disability . It is sensitive to change following bronchodilation in subjects with CAL , although the change correlates less well with improvements in FEV1 . Overall , these results suggest that the SWT might be an appropriate measure to assess interventions in elderly people", "Spencer LM , Alison JA , McKeough ZJ : Six-minute walk test as an outcome measure : are two six-minute walk tests necessary immediately after pulmonary rehabilitation and at three-month follow-up ? Am J Phys Med Rehabil 2008;87:224–228.A 3-mo prospect i ve , longitudinal , repeated- measures study was undertaken in subjects with chronic obstructive pulmonary disease ( COPD ) . The study aim ed to determine whether there was a difference in 6-min walk distance ( 6MWD ) when two 6-min walk tests were performed after pulmonary rehabilitation ( n = 44 ) and at 3-mo follow-up ( n = 40 ) , and whether the results reflected the program outcomes . There was a significant increase in 6MWD between two 6-min walk tests before rehabilitation ( P 6MWD from before to after pulmonary rehabilitation ( P Six-minute walk tests performed twice before and after pulmonary rehabilitation programs and at 3-mo follow-up assessment s ensure accuracy of measurement of the 6MWD and program outcomes", "OBJECTIVES ( 1 ) To examine the concurrent criterion validity of the modified shuttle walk test ( MSWT ) by using the 6- ( 6MWT ) and 12-minute walk test ( 12MWT ) , ( 2 ) to examine the concurrent criterion validity of the estimated maximum oxygen uptake ( Vo2max ) of the MSWT with actual Vo2max , and ( 3 ) to determine test-retest reliability of the MSWT in patients with chronic obstructive pulmonary disease ( COPD ) . DESIGN Validation study . SETTING Outpatient pulmonary rehabilitation program . PARTICIPANTS Thirty clinical ly stable adults with COPD . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Subjects were r and omly assigned to receive either the 6MWT and 12MWT or the MSWT first . The MSWT was repeated 1 week later ( N = 30 ) . Estimated Vo2max was calculated , and actual Vo2max was conducted by using the Jones test . Validity of the MSWT was assessed by comparing endurance scores and Vo2max with results from the 6MWT and 12MWT and Jones test , respectively . RESULTS There was a moderately high correlation between the MSWT and the 6MWT and 12MWT at initial testing ( .82 and .74 , respectively ) . Correlation between estimated and actual Vo2max was r equal to .68 . Test-retest reliability for the entire sample was high ( intraclass correlation coefficient , .88 ) . Results remained quite stable across severity , age , and sex subgroups . CONCLUSIONS The MSWT is a st and ardized externally paced submaximal endurance walking test . The results indicate that the MSWT has high concurrent validity and test-retest reliability for patients with COPD", "The need for a 6-min walk distance ( 6-MWD ) reference equation for healthy North African adults older than 40 years was assessed in a prospect i ve cross-sectional study . Anthropometric data and 6-MWD were measured in 229 healthy Tunisian adults ( 125 women ) over 40 years old . Two subgroups of 38 women were identified according to the parity ( low or=6 ) . The published reference equations did not reliably predict measured 6-MWD . The 6-MWD was significantly correlated with gender , age , weight and height ( p 6-MWD decline ( r=-0.39 , p or=6 ) showed different 6-MWD ( 589+/-60 m vs. 555+/-57 m , p 6-MWD was satisfactory . In conclusion , this reliable 6-MWD reference equation enriches the World Bank and provides an important element of interpretation for women with high parity ", "OBJECTIVES To investigate cardiorespiratory and dyspnea responses to incremental and self-paced exercise tests in patients with COPD . DESIGN A prospect i ve within-subject design was used . PATIENTS Twenty stable subjects ( 15 men ) , with a mean ( + /- SD ) age of 64.0 + /- 7.5 years and moderate-to-severe COPD ( ie , mean FEV(1 ) , 0.8 + /- 0.3 L and 28.9 + /- 7.9 % predicted ) were studied . METHODS Each subject completed a 6-min walk test ( 6MWT ) , an incremental shuttle walking test ( ISWT ) , and a cycle ergometer test ( CET ) , within a 2-week period . The tests were performed at least 24 h apart . St and ardized encouragement was utilized in each test with the aim of maximizing performance . Heart rate ( HR ) and dyspnea were measured each minute throughout the tests , and pulse oximetric saturation ( Spo(2 ) ) was measured before and immediately after each test . The distances walked in the 6MWT and ISWT were compared to peak oxygen uptake ( Vo(2 ) ) values from the CET . RESULTS HR increased linearly with increasing workload during the CET and ISWT , but increased alinearly with a disproportionate increase early in the 6MWT . In contrast , dyspnea scores increased linearly during the 6MWT , but increased alinearly with a disproportionate increase late during the CET and ISWT . Peak HR and dyspnea were not significantly different between tests . Spo(2 ) was significantly lower at the end of both walking tests compared to that at the end of the CET ( p distance walked in both the ISWT and 6MWT were related to peak Vo(2 ) values on the CET ( for both tests , r = 0.73 ; p response in HR and dyspnea seen during the 6MWT suggest that patients with COPD titrate exertion against dyspnea to achieve a peak tolerable intensity . This strategy is not possible in an externally paced ISWT or CET . However , it is a limited strategy , with performance converging at higher workloads . Similar peak exercise responses were achieved in the 6MWT , ISWT , and CET . Greater oxygen desaturation was observed during the field walking tests , suggesting that both the ISWT and 6MWT are more sensitive than the CET in detecting exercise-induced hypoxemia and in assessing ambulatory oxygen therapy needs ", "Background : The 6-min walk test ( 6MWT ) is increasingly used as an outcome measure in interstitial lung disease ( ILD ) . Aim : To evaluate the usefulness of the 6MWT in a cohort of patients with ILD secondary to systemic sclerosis ( SSc ) and to correlate with established physiological parameters . Methods : 163 patients with SSc-ILD were recruited for a multicentre , r and omised , double-blind clinical trial . Available data at protocol screening included repeated 6MWTs , pulmonary function testing with diffusing capacity , Doppler echocardiography and high-resolution computed tomography of the thorax . Borg Dyspnoea Index was evaluated before and after 6MWT . Results : Mean ( st and ard deviation ( SD ) ) distance walked during walk test 1 was 396.6 ( 84.55 ) m compared with 399.5 ( 86.28 ) m at walk test 2 . The within-subject , intertest correlation as determined by Pearson ’s correlation coefficient testing was 0.95 ( p with percentage forced vital capacity and the Borg Dyspnoea Index were observed , and no correlation was observed with percentage diffusing capacity . Conclusion : These data confirm the high reproducibility of the 6MWT in patients with SSc-ILD and therefore the validity of the test in this cohort . The lack of correlation of 6MWT with st and ard physiological parameters of ILD suggests a multifactorial basis for limited exercise capacity in patients with SSc and calls into question the utility of the 6MWT as a measure of outcome in future studies on SSc-ILD", "The purpose of the present study was to compare the characteristics of three different exercise tests in evaluating the effects of oxitropium bromide on exercise performance . Thirty-eight males with stable chronic obstructive pulmonary disease ( COPD ) ( FEV(1 ) = 40.8 + /- 16.5 % predicted ; mean + /- SD ) completed r and omized , double-blind , placebo-controlled , crossover studies for each exercise test . The exercise tests were performed 60 min after the inhalation of either oxitropium bromide 400 microg or placebo . The patients performed 6-min walking tests ( 6MWT ) on Days 1 and 2 , progressive cycle ergometry ( PCE ) on Days 3 and 4 , and cycle endurance tests at 80 % of the maximal workload of PCE on Days 5 and 6 . Spirometry was conducted before and at 45 and 90 min after the inhalation . Oxitropium bromide significantly increased FEV(1 ) as compared with placebo . Oxitropium bromide increased the endurance time significantly , by 19 % ( p 6-min walking distance by 1 % ( p maximal oxygen consumption ( V O(2)max ) in PCE . The responses in these three exercise tests were different , and we conclude that the endurance test was the most sensitive in detecting the effects of inhaled anticholinergic agents on exercise performance in patients with stable COPD . An endurance procedure may be performed to detect clinical changes in evaluating the effects of oxitropium bromide on exercise performance", "STUDY OBJECTIVES To assess oxygen desaturation during activities and to evaluate the short-term effects of supplemental O(2 ) use in patients with severe COPD who do not qualify for long-term O(2 ) therapy . DESIGN A double-blind , r and omized , placebo-controlled trial . SETTING Out patients from the pulmonary diseases division of a tertiary-care university hospital . PATIENTS Twenty patients with stable COPD with FEV(1)/FVC ratios of 60 mm Hg when resting . INTERVENTIONS Patients were initially evaluated with pulmonary function tests , blood gas analysis , and Doppler echocardiography , and they underwent the following three 6-min walking tests ( WTs ) in a r and om sequence : basal WT ( BWT ) ; WT while breathing compressed air ( CAWT ) ; and WT while breathing O(2 ) ( O(2)WT ) . MEASUREMENTS AND RESULTS The distance walked was recorded in meters . Dyspnea was measured by Borg scale measurement before and after the tests , and arterial oxygen saturation measured by pulse oximetry ( SpO(2 ) ) was continuously monitored . Results were analyzed by grouping patients in the following manner : desaturators ( DSs ) ( ie , patients with a drop in SpO(2 ) of at least 5 % and walked and /or a decrease of at least 3 points in Borg index score ) vs nonresponders . During the BWT , 11 of 20 patients ( 55 % ) were defined as desaturators . During the O(2)WT , the SpO(2 ) remained at > 90 % in every patient . The distance walked increased by 22 % ( p dyspnea decreased 36 % ( p ) administration reduced dyspnea by 47 % ( p distance walked did not improve . Responses were markedly different from one patient to another . No significant differences were noticed between the results of the BWT and CAWT in any of the groups . Thirteen O(2 ) responders did not differ from 7 nonresponders either in basal data or in desaturation measure during the BWT , except that all walking responders ( five patients ) were above the median of basal left ventricle performance . CONCLUSIONS Most of the studied COPD patients desaturated during the BWT . O(2 ) administration avoided desaturation and could increase the distance walked and reduce dyspnea , but these effects were not related to walking desaturation in individual cases . Improvements were not a placebo effect . The therapeutic role of O(2 ) during activities in some patients with severe COPD needs to be individually assessed", "BACKGROUND Exercise training programmes for patients with COPD are effective in improving exercise capacity . The few trials that have investigated the effects of exercise programmes on daily physical activity show contradictory results . AIM To investigate the relation between daily physical activity level and exercise capacity in patients with COPD using data of a r and omised controlled trial in which the exercise intervention was aim ed at improvement of both physical activity and exercise capacity ( the COPE-II study ) . METHODS These are secondary analyses of the COPE-II study , a r and omised controlled trial in which a community-based physiotherapeutic exercise programme was evaluated . Daily physical activity was measured with a pedometer ( steps/day ) . Exercise capacity was measured with an incremental maximal cycle ergometer test , the incremental ( ISWT ) and endurance shuttle walk test ( ESWT ) . Pearson correlation coefficients were calculated . RESULTS At baseline , correlations between steps/day and VO(2peak ) , ISWT ( m ) , ESWT ( m ) and ESWT ( s ) were 0.54 , 0.59 , 0.44 , and 0.34 , respectively ( all p intervention group , correlations between change in steps/day over 7 months and change in ISWT ( m ) , ESWT ( m ) and ESWT ( s ) were 0.47 , 0.41 , and 0.38 , respectively ( all p control group , these same correlations were weak to non-existent . CONCLUSIONS A moderate to weak relationship was found between daily physical activity and exercise capacity . These results strengthen our beliefs that exercise interventions need to target not only exercise capacity but also behaviour change with regard to daily physical activity to achieve improvements in both parameters", "RATIONALE Although commonly used as the primary outcome measure of clinical trials in pulmonary arterial hypertension ( PAH ) , the minimal important difference ( MID ) of the 6-minute walk test ( 6MWT ) has not been well defined for this population of patients . OBJECTIVES To estimate the MID in the 6MWT in patients with PAH . METHODS Study subjects from the clinical trial of tadalafil in PAH , a 16-week , parallel-group , r and omized clinical trial of patients who were treatment naive or on background therapy with an endothelin receptor antagonist , were eligible . 6MWT was performed using a st and ardized protocol . Distributional and anchor-based methods were used to estimate the MID ; the latter method used the Physical Component Summary Score ( PCS ) of the Medical Outcomes Study 36-item short form ( SF-36 ) . MEASUREMENTS AND MAIN RESULTS Four hundred five subjects were analyzed . Domains of the SF-36 were weakly to modestly associated with 6MWT . Change in the PCS of the SF-36 was most strongly associated with change in 6MWT ( r = 0.40 , P MID ranging from 25.1 to 38.5 m , whereas anchor-based analyses yielded an estimate of 38.6 m. CONCLUSIONS Using both distributional and anchor-based methods , the estimated consensus MID in the 6MWT for PAH is approximately 33 m. These results have important implication s for ( 1 ) assessing treatment responses from clinical trials and metaanalyses of specific PAH therapy , and ( 2 ) sample size calculations for future study design", "The 6-min walk test ( SMWT ) performed in the hallway ( HW ) is used as a clinical indicator of functional capacity in patients with lung disease . A 6-min walk test utilizing a treadmill ( TM ) is easier to perform and allows easier patient monitoring . Therefore , we formulated a st and ardized TM SMWT protocol and compared the results with those of a HW SMWT . All patients were enrolled in a pulmonary rehabilitation program . Patients with current infection , recent change in inhaled medications or oral steroid use , and significant cardiovascular disease were excluded . Each subject performed three HW SMWTs and three TM SMWTs assigned r and omly on subsequent days . There was a 30-min rest between each walk and at least a 48-h rest between each test day . All patients completed both HW and TM SMWT within 7 d. Supplemental oxygen was utilized or increased if the saturation fell below 88 % . The best of the three tests was used for data analysis . Twenty-one subjects completed the protocol . The mean age was 65 + /- 10.9 yr ( range , 35 to 79 yr ) . Ten subjects were receiving supplemental oxygen . The mean FEV(1 ) was 1.07 + /- 0.53 L. The mean HW SMWT distance was 1,228 + /- 255 ft ( range , 612 to 1,679 ft ) and the mean TM SMWT distance was 1,060 + /- 389 ft ( range , 475 to 1,819 ft ) , which were statistically different ( p = 0.01 ) . The mean difference was 168 + /- 280 ft ( range , -326 to 743 ft ) . Oxygen saturation and supplemental oxygen requirements did not differ significantly . The intra-test variability of the three HW SMWTs was similar to the three TM SMWTs and no significant difference in the coefficient of variation was found . A st and ardized TM SMWT is feasible and allows easier patient monitoring , but there is a statistically significant difference between the HW and TM SMWT distance and therefore they are not interchangeable . However , the intratest reproducibility of the TM and HW SMWTs are similar when three walks are performed in a single test session . The role of the TM SMWT in pulmonary rehabilitation requires further exploration", "BACKGROUND : The development of portable liquid oxygen systems , capable of delivering high flow rate oxygen for long periods , justifies re assessment of the value of supplemental oxygen to aid exercise tolerance in patients with chronic respiratory insufficiency . The type of exercise test and the low oxygen flow rates previously used may account for the variable and often poor responses to supplemental oxygen reported in earlier studies . METHODS : The walking tolerance of 30 patients with severe respiratory disability was measured while they were breathing air and increasing doses of supplemental oxygen ( 2 , 4 , 6 1/min ) by using both the st and ard six minute walking test and an endurance walking test . To assess the initial learning effect and repeatability of the walking tests , three six minute walks and three endurance walks were performed on day 1 and a single walk of each type on days 2 , 3 , and 14 . In addition , oxygen dosing studies were performed on days 2 and 3 after the initial baseline walking tests . Each dosing study comprised four endurance walking tests or four six minute walking tests with patients breathing either air at a flow rate of 4 1/min from a portable cylinder or supplemental oxygen at a flow rate of 2 , 4 or 6 1/min from a portable liquid oxygen supply . The order of the tests was r and omised . Walking distance with each flow rate of oxygen was compared with walking distance with patients carrying cylinder air and for the initial unburdened walks . Breathlessness was assessed by visual analogue scoring on completion of each walk . RESULTS : Exercise ability and breathlessness were significantly improved with supplemental oxygen and this benefit outweighed the reduction in performance result ing from carrying the portable device . Supplemental oxygen at flow rates of 2 , 4 , and 6 1/min increased mean endurance walking distances by 37.9 % , 67.7 % and 85.0 % and six minute walking distances by 19.2 % , 34.5 % , and 36.3 % by comparison with distances when the patient was carrying air with a flow rate of 4 1/min . The additional work of carrying the portable gas supply reduced endurance walking distance by 22.2 % and six minute walking distance by 14.1 % by comparison with a baseline unburdened walk . Comparison of supplemental oxygen at 2 , 4 , and 6 1/min with the baseline unburdened performance showed increased endurance walking distances of 7.3 % , 30.4 % , and 43.9 % and six minute walking distances of 2.3 % , 15.5 % , and 17.0 % . Walking distance was increased by more than 50 % by comparison with an unburdened walk in seven patients with the endurance walking test but in only three patients with the six minute walking test . The benefit was similar in patients with obstructive and with interstitial lung disease . Individual responses were variable and only desaturation during the baseline walk in patients with obstructive lung disease had any predictive value for benefit with oxygen . CONCLUSION : As there was no clear relation between response to oxygen therapy and the patients ' characteristics , assessment for supplemental oxygen therapy will depend on exercise testing . It is suggested that portable oxygen should be considered only if a patient shows a 50 % improvement in exercise ability with high flow rate oxygen ( 4 - 6 1/min ) by comparison with an unburdened walk", "It is unclear whether short-term benefits from supplemental oxygen translate into improved quality of life in patients with severe COPD . In a 12 wk double-blind r and omized crossover study , we assessed the effects of supplemental air and oxygen on exercise performance ( step tests and 6 min walking distance [ 6MWD ] ) initially and after two 6 wk periods at home using exertional cylinder air or oxygen . We measured quality of life at baseline and after the two 6 wk domiciliary periods . The 26 patients ( 24 males ) had a mean age of 73 + /- 6 yr ; mean FEV1 , 0.9 + /- 0.4 L ; mean DLCO , 10.6 + /- 2.4 ml/min/mm Hg ; mean resting PO2 , 69 + /- 8.5 ( range 58 to 82 ) mm Hg ; mean PCO2 , 41 + /- 3.3 mm Hg ; and mean resting SaO2 , 94 + /- 2.1 ( mean + /- SD ) . Laboratory tests were performed breathing intranasal air or oxygen at 4 L/min , and measurements were made of SaO2 and Borg dysnea scores . Supplemental oxygen increased 6MWD and steps by small , statistically significant increments acutely at baseline and after 6 and 12 wk , without corresponding falls in Borg score . Degree of desaturation at baseline did not correlate with increase in 6MWD or steps achieved at baseline or at 6 or 12 wk , nor with the domiciliary gas used . There was no difference in 6MWD or steps achieved while breathing supplemental oxygen after 6 wk of domiciliary oxygen compared with domiciliary air . Small improvements in quality of life indices were found after domiciliary oxygen , and mastery also improved after domiciliary air . There were no differences in quality of life , however , when domiciliary oxygen was compared with domiciliary air . Although oxygen supplementation induced small acute increments in laboratory exercise performance , such improvements had little impact on the patients ' daily lives", "Resting pulmonary function and exercise variables are widely used to stage and monitor idiopathic interstitial pneumonia ( IIP ) . However , the variability of exercise data ( maximal exercise and the 6-minute walk test ) has not been evaluated definitively . We have prospect ively quantified the reproducibility of resting and exercise functional data in fibrotic IIP ( idiopathic pulmonary fibrosis , fibrotic nonspecific interstitial pneumonia ) and have evaluated interrelationships between variables . Thirty consecutive patients with fibrotic IIP underwent serial resting pulmonary function tests , 6-minute walk ( n = 29 ) , and maximal exercise ( n = 24 ) at an interval of 1 week , with all testing performed in accordance with American Thoracic Society st and ards . Within-subject reproducibility was excellent for 6-minute walk distance ( SD/mean = 4.2 % ) and clinical ly acceptable for resting pulmonary function indices and VO(2)max on maximal exercise testing . However , the amplitude of oxygen desaturation at the end of exercise was poorly reproducible in both 6-minute walk and maximal exercise testing ( SD/mean > 25 % ) . There was a highly significant relationship between VO2max on maximal exercise testing and 6-minute walk distance ( r(s ) = 0.78 , p 6-minute walk distance is a major advantage in routine staging and monitoring , whereas maximal exercise variables are poorly reproducible", "BACKGROUND The goal of the 6-min walk test ( 6MWT ) is to enable patients to walk \" as far as possible \" as a measure of their functional ability . The impact of the specific walk instructions on patient 6MWT performance is unknown . METHODS Patients with pulmonary arterial hypertension ( PAH ) , idiopathic pulmonary fibrosis ( IPF ) , and other forms of interstitial lung disease ( ILD ) were recruited to perform four identical 6MWTs with one differing instructional phrase . The st and ard instruction to walk \" as far as possible \" was substituted in r and om order with \" as fast as possible , \" \" at your normal pace , \" or \" at a leisurely pace . \" RESULTS Twenty-four patients ( 10 with PAH , eight with IPF , six with other ILD ) were enrolled and completed all four 6MWTs . Patients attained the greatest distance with the fast instruction , exceeding the st and ard instruction distance by a mean of 52.7 m ( P mean difference between the fast and st and ard walks was 41.5 m in the PAH group , 66.5 m in the IPF group , and 53 m in the other ILD group . CONCLUSIONS Patients do not walk as far as they are able with the st and ard American Thoracic Society instruction for 6MWT . Changing the wording from \" far \" to \" fast \" may facilitate a better effort and greater distance during the test . It is possible that this modified 6MWT instruction may result in improved accuracy and reproducibility , thereby enhancing its clinical and research trial usefulness", "BACKGROUND There has been no direct comparison between an incremental and endurance walking test to detect the relative oxygen desaturation in patients with chronic obstructive pulmonary disease ( COPD ) . This is of some importance as current guidelines have suggested that ambulatory oxygen should only be prescribed after a st and ard assessment and desaturation documented . No clear advice about the nature of the required exercise task is given . This study therefore compared the relative desaturation between the incremental shuttle walking test ( ISWT ) and the constant speed walking test ( ESWT ) and response to ambulatory oxygen . METHODS Forty-one patients ( 29 male ) , mean ( SD ) , age 71.18 ( 7.48 ) yrs , FEV(1 ) 0.85 ( 0.29 ) l with stable COPD were recruited after completion of a 7-week pulmonary rehabilitation programme . Patients completed a baseline ( without carrying a cylinder ) ISWT and ESWT and then , in r and om order in double blind fashion , completed the walk tests with a cylinder of air or a cylinder of oxygen . Measurements included distance walked , oxygen saturation , heart rate , perceived breathlessness and exertion ( Borg scale ) . RESULTS All patients desaturated ( desaturation between the ISWT and the ESWT . There was a significant improvement in performance with supplementary oxygen compared to cylinder air ( p distance walked for either test . There was a significant decrease in walking performance on both the ISWT and the ESWT when carrying an air cylinder compared with the control walk . When comparing the percentage difference between oxygen and air for responders ( i.e. those that achieve a 10 % or more increase ) , the ESWT showed a greater percentage change 42.1 % compared to 26.1 % for the ISWT . CONCLUSIONS This study identifies that incremental and endurance walking provokes significant desaturation and that there is a short-term benefit of oxygen versus air in enhancing exercise performance . There was no significant difference in the level of desaturation between tests . Therefore the ISWT is a suitable exercise test that can be used to evaluate desaturation and is practically more realistic", "In a prospect i ve , r and omized study we examined the effect of ( i ) ambulatory oxygen and ( ii ) a portable , inspiratory pressure support ( IPS ) device on the endurance shuttle walk test ( ESWT ) in patients with severe chronic obstructive pulmonary disease ( COPD ) . Ten out patients [ median ( range ) FEV1 0.60 l(0.35 , 1.45 ) ] performed the ESWT under five test conditions : baseline walk ( no assistance ) , IPS at 14 cmH2O from a portable ventilator ( the HIPPY , Friday Medical , U.K. ) , sham IPS ( ambulatory oxygen at 2 l min(-1 ) , and sham oxygen ( carrying the portable oxygen cylinder and breathing air ) . There were significant improvements in the ESWT with ambulatory oxygen , but a negative effect with the HIPPY device [ mean ( SD ) time : baseline 172 ( 48 ) sec ; oxygen 242 ( 62 ) sec ; HIPPY 84 ( 35 ) sec ] . The ESWT appeared sensitive to the effect of cylinder weight although differences in endurance capacity were not significant [ sham oxygen 151 ( 45 ) sec ] . The ESWT was sensitive to the acute application of oxygen , demonstrating a beneficial effect on endurance performance in patients with severe COPD . The ESWT could form the basis of a st and ardized assessment for ambulatory oxygen", "OBJECTIVE To establish the minimal important difference ( MID ) for the six-minute walk distance ( 6MWD ) in persons with chronic obstructive pulmonary disease ( COPD ) . DESIGN Analysis of data from an observational study using distribution- and anchor-based methods to determine the MID in 6MWD . SETTING Outpatient pulmonary rehabilitation program at 2 teaching hospitals . PARTICIPANTS Seventy-five patients with COPD ( 44 men ) in a stable clinical state with mean age 70 years ( SD 9 y ) , forced expiratory volume in one second 52 % ( SD 21 % ) predicted and baseline walking distance 359 meters ( SD 104 m ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Participants completed the six-minute walk test before and after a 7-week pulmonary rehabilitation program . Participants and clinicians completed a global rating of change score while blinded to the change in 6MWD . RESULTS The mean change in 6MWD in participants who reported themselves to be unchanged was 17.7 meters , compared with 60.2 meters in those who reported small change and 78.4 meters in those who reported substantial change ( P=.004 ) . Anchor-based methods identified an MID of 25 meters ( 95 % confidence interval 20 - 61 m ) . There was excellent agreement with distribution-based methods ( 25.5 - 26.5 m , kappa=.95 ) . A change in 6MWD of 14 % compared with baseline also represented a clinical ly important effect ; this threshold was less sensitive than for absolute change ( sensitivity .70 vs .85 ) . CONCLUSIONS The MID for 6MWD in COPD is 25 meters . Absolute change in 6MWD is a more sensitive indicator than percentage change from baseline . These data support the use of 6MWD as a patient-important outcome in research and clinical practice", "Background : Despite widespread use of the incremental shuttle walk distance ( ISWD ) , there are no reference equations for predicting it . Objectives : We aim ed to evaluate ISWD in healthy subjects and to establish a reference equation for its prediction . Methods : 131 Brazilian individuals ( 61 males ; 59 ± 10 years ) performed 2 walk tests in a 10-m long corridor . We assessed height , weight , body mass index , forced expiratory volume in 1 s , forced vital capacity and self-reported physical activity . Results : Mean ISWD was greater in males than in females ( 606 ± 167 vs. 443 ± 117 m ; p ) . ISWD correlated significantly ( p ISWD variance . In an additional group of 20 subjects prospect ively studied , the difference between measured and predicted ISWD was not statistically significant ( 534 ± 84 vs. 552 ± 87 m , respectively ) , representing 97 ± 12 % of the predicted value calculated with our reference equation for ISWD . Conclusions : This reference equation including demographic and anthropomorphic attributes could be useful for interpreting the walking performance of patients with chronic diseases that affect exercise capacity", "STUDY OBJECTIVES This study was conducted to examine the short-term effects of using a rollator on functional exercise capacity among individuals with COPD and to characterize which individuals benefit most from its use . DESIGN Repeated- measures r and omized crossover design using the 6-min walk test ( 6MWT ) as the primary outcome measure . SETTING Respiratory rehabilitation center . PATIENTS Forty stable subjects who had received a diagnosis of COPD . INTERVENTIONS Two 6MWTs were performed on each study day . One 6MWT was performed unaided , and the other was performed with a rollator . The order was r and omized on the first day and reversed on the second day . RESULTS Use of the rollator was associated with a significant reduction in dyspnea ( p and duration of rest ( reduction for the total group , 19 s ; and reduction for those who walked distance walked ( p = 0.02 ) . No changes were found for the measures of cardiorespiratory function or gait ( p > 0.05 ) . The requirement to rest during an unaided 6MWT was a significant predictor of improved functional exercise capacity with the use of the rollator ( p rollator to walking unaided . CONCLUSIONS Use of a rollator was effective in improving functional exercise capacity by reducing dyspnea and rest duration among stable individuals with severe COPD . Individuals who walked rollator in terms of reduced dyspnea , reduced rest time , and improved distance walked", "QUESTIONS Do patients with chronic obstructive pulmonary disease ( COPD ) achieve a different distance on the six minute walk test ( 6MWT ) conducted on a 10 m course versus on a 30 m course ? When assessing the distance on a 6MWT conducted on a 10 m course , is it valid to use existing reference equations that were generated on longer courses ? DESIGN A r and omised double-crossover experimental study . PARTICIPANTS Forty-five patients with COPD in primary physiotherapy care . INTERVENTION All patients performed a 6MWT twice over a 10 m course and twice over a 30 m course . The 6MWTs were performed in accordance with the American Thoracic Society guidelines . OUTCOME MEASURES 6MWD was assessed and predicted distance was calculated based on a range of reference equations . RESULTS The 6MWD on the 10 m course was 49.5 m shorter than on the 30 m course , which was statistically significant ( 95 % CI 39.4 to 59.6 ) . By using existing reference equations for a 6MWT conducted on the 10 m course , the predicted distance is highly overestimated ( with a range of 30 % to 33 % ) and the average distance as a percentage of the predicted value is 8%pred lower compared to a 6MWT conducted on the 30 m course , result ing in a worse representation of a COPD patient 's functional exercise capacity . CONCLUSION This study shows that the impact of course length on the 6MWD and on the use of reference equations in patients with COPD is substantial and clinical ly relevant ( based on the most conservative published minimum clinical ly important difference ) . Therefore , existing reference equations established for a 6MWT conducted over a 30 m ( or longer ) course can not be applied to predict the distance achieved on the 6MWT on a 10 m course , which is frequently used in primary care physiotherapy practice s for patients with COPD", "In a large , prospect ively followed , two‐center cohort of patients listed for lung transplantation ( n = 376 ) , we used Cox proportional hazards models to determine the importance of baseline 6‐min walk distance ( 6MWD ) in predicting patient survival . 6MWD used as a continuous variable was a significant predictor of survival after adjusting for other important covariates when transplant was considered as a time‐varying covariate ( HR for each 500 ft increase in 6MWD = 0.57 , 95 % CI : 0.43–0.77 , p = 0.0002 ) . 6MWD remained an important predictor of survival in models that considered only survival to transplant ( HR for each 500 ft increase in 6MWD = 0.41 , 95 % CI : 0.27–0.62 , p or survival only after transplant ( HR for each 500 ft increase in 6MWD = 0.40 , 95 % CI : 0.22–0.72 , p = 0.002 ) . Unadjusted Kaplan‐Meier analysis demonstrates significantly different survival by 6MWD tertiles ( 1200 ft , p‐value = 0.0001 ) . In the overall model , 6MWD prediction of survival was relatively homogeneous across disease category ( 6MWD by disease interaction term , p‐value = 0.63 ) . Our results demonstrate a significant relationship between baseline 6MWD and survival among patients listed for lung transplantation that exists across all native disease categories and extends through transplantation . The 6MWD is thus a useful measure of both urgency and utility among patients awaiting lung transplantation", "BACKGROUND In patients with idiopathic pulmonary fibrosis ( IPF ) , our objectives were to identify predictors of abnormal heart rate recovery ( HRR ) at 1 min after completion of a 6-min walk test ( 6MWT ) [ HRR1 ] and 2 min after completion of a 6MWT ( HRR2 ) , and to determine whether abnormal HRR predicts mortality . METHODS From 2003 to 2008 , we identified IPF patients who had been evaluated at our center ( n = 76 ) with a pulmonary physiologic examination and the 6MWT . We used logistic regression to identify predictors of abnormal HRR , the product-limit method to compare survival in the sample stratified on HRR , and Cox proportional hazards analysis to estimate the prognostic capability of abnormal HRR . RESULTS Cutoff values were 13 beats for abnormal HRR1 and 22 beats for HRR2 . In a multivariable model , predictors of abnormal HRR1 were diffusing capacity of the lung for carbon monoxide ( odds ratio [ OR ] , 0.4 per 10 % predicted ; 95 % confidence interval [ CI ] , 0.2 to 0.7 ; p = 0.003 ) , change in heart rate from baseline to maximum ( OR , 0.9 ; 95 % CI , 0.8 to 0.97 ; p = 0.01 ) , and having a right ventricular systolic pressure > 35 mm Hg as determined by transthoracic echocardiogram ( OR , 12.7 ; 95 % CI , 2.0 to 79.7 ; p = 0.01 ) . Subjects with an abnormal HRR had significantly worse survival than subjects with a normal HRR ( for HRR1 , p = 0.0007 [ log-rank test ] ; for HRR2 , p = 0.03 [ log-rank test ] ) ; these results held for the subgroup of 30 subjects without resting pulmonary hypertension ( HRR1 , p = 0.04 [ log-rank test ] ) . Among several c and i date variables , abnormal HRR1 appeared to be the most potent predictor of mortality ( hazard ratio , 5.2 ; 95 % CI , 1.8 to 15.2 ; p = 0.004 ) . CONCLUSION Abnormal HRR after 6MWT predicts mortality in IPF patients . Research is needed to confirm these findings prospect ively and to examine the mechanisms of HRR in IPF patients", "RATIONALE Breathing supplemental oxygen reduces breathlessness during exercise in patients with chronic obstructive pulmonary disease ( COPD ) . Replacing nitrogen with helium reduces expiratory flow resistance and may improve lung emptying . Combining these treatments should be independently effective . OBJECTIVES Study the effect of changing oxygen or helium concentration in inspired gas during exercise in patients with stable COPD . METHODS In 82 patients ( mean age , 69.7 yr ; mean FEV(1 ) , 42.6 % predicted ) , we measured endurance shuttle walking distance , resting and exercise oxygen saturation , and end-exercise dyspnea ( Borg scale ) while patients breathed Heliox28 ( 72 % He/28 % O(2 ) ) , Heliox21 ( 79 % He/21 % O(2 ) ) , Oxygen28 ( 72 % N(2)/28 % O(2 ) ) , or medical air ( 79 % N(2)/21 % O(2 ) ) . Gases were administered using a r and omized , blinded , crossover design via a face mask and an inspiratory dem and valve . RESULTS Breathing Heliox28 increased walking distance ( mean+/-SD , 147+/-150 m ) and reduced Borg score ( -1.28+/-1.30 ) more than any other gas mixture . Heliox21 significantly increased walking distance ( 99+/-101 m ) and reduced dyspnea ( Borg score , -0.76+/-0.77 ) compared with medical air . These changes were similar to those breathing Oxygen28 . The effects of helium and oxygen in Heliox28 were independent . The increase in walking distance while breathing Heliox28 was inversely related to baseline FEV(1 ) breathing air . CONCLUSION Reducing inspired gas density can improve exercise performance in COPD as much as increasing inspired oxygen . These effects can be combined as Heliox28 and are most evident in patients with more severe airflow obstruction", "Background : The 6-minute walk distance ( 6MWD ) has been useful in the evaluation of men with COPD . Little is known about 6MWD in women with the disease . Objectives : Using healthy women as a reference , to evaluate the factors that help determine 6MWD in women with COPD . To explore if the 350 meters threshold differentiates survival in women as it does in men . Methods : Healthy women ( n = 164 ) and with COPD ( n = 223 ) were included in the study . Age , pack-years history , smoking status , comorbidities ( Charlson Index ) , BMI , MRC dyspnea , spirometry and 6MWD were recorded in all participants and PaO2 and IC/TLC in COPD women . The patients were prospect ively followed and deaths registered . Factors predicting 6MWD were determined by multiple regression analysis . ROC analysis was used to calculate the best threshold value for the 6MWD with mortality as gold st and ard . Kaplan-Meier curves compared survival of patients that walked more or less than 350 m by age categories . Results : The 6MWD is decreased in women with COPD . Values decrease with age and GOLD stages . Age , BMI , smoking status , comorbidities , MRC and FEV1 % are statistical significant predictors of 6MWD . A 350 m cut-off value has a good sensitivity and specificity to predict ( 73 % and 80 % respectively ) and differentiate survival ( p women with COPD , the 6MWD decreases with age and GOLD stages . A 350 m distance is a valid threshold to differentiate survival . Further studies in different setting s should confirm our findings", "The product of walking distance and body weight ( D x W ) mimics the work of walking . We hypothesized the superiority of D x W to walking distance ( D ) alone in any correlation with lung function , anaerobic threshold ( AT ) and maximal oxygen uptake ( VO2max ) . We further hypothesized that the D x W product for a 6-min walk test ( 6 MWT ) would correlate with the AT and VO2max because all three are markers of exercise ability . Thirty-three male chronic obstructive pulmonary disease ( COPD ) patients with mean forced expiratory volume in 1 sec ( FEV1 ) of 1.2+/-0.4 l ( range 0.58 - 1.86 l ) were enrolled . Six patients were excluded due to inability to achieve a maximal test . Lung function and self-assessed every-day activities using a oxygen-cost diagram were evaluated before entry of the study . A maximal effort ramp-pattern cardiopulmonary exercise test ( CPET ) and a 6 MWT were conducted in r and om order . Borg score , heart rate , and O2 saturation with pulse oximetry ( SpO2 ) were measured during both exercise tests . VO2 AT and minute ventilation were also measured during the CPET . Correlations were sought between the distance covered in the 6 MWT , and the D x W product with AT , VO2max and other variables . The average D and D x W were 456 m and 27.5 kg km(-1 ) , respectively . D x W was superior to D alone when correlated with the VO2max and AT determined from the CPET , while modestly correlated with the change ( delta ) in Borg score and delta SpO2 in the 6 MWT and self-assessed every-day activities . Distance x weight product was correlated with the AT and VO2max . In addition , D x W was better correlated with diffusing capacity for carbon monoxide and vital capacity than D alone . We conclude that D x W mimics the work of walking better than D and is suggested as a parameter for evaluation of patients ' fitness if gas exchange measurements are not available", "BACKGROUND Different exercise tests are used to evaluate the functional capacity in chronic obstructive pulmonary disease . The cardiopulmonary exercise test is considered the gold st and ard , but the 6 minute walk and the 15 step exercise oximetry test are considerably less expensive . OBJECTIVES To determine whether reliable data could be obtained at lower cost . METHODS The study sample consisted of 50 patients with mild to severe stable COPD . All underwent pulmonary function test and the cardiopulmonary exercise test , 6 minute walk and 15 step exercise oximetry test as part of their regular follow-up visit . Functional capacity was grade d according to each test separately and the functional capacities obtained were correlated . RESULTS The results showed that most of the patients had severe COPD according to pulmonary function tests ( mean forced expiratory volume in the first second 46.3 + /- 19.9 % of predicted value ) . There was a good correlation between the cardiopulmonary exercise test and the 6 minute walk functional capacity classes ( r = 0.44 , P = 0.0013 ) . We did not find such correlation between the 15 step exercise oximetry test and the cardiopulmonary exercise test ( r = 0.07 , P = 0.64 ) . CONCLUSIONS The study shows that the 6 minute walk is a reliable and accurate test in the evaluation of functional capacity in COPD patients", "BACKGROUND Fatigue is a frequently occurring symptom in patients with chronic obstructive pulmonary disease ( COPD ) . Despite this , relatively few studies have objective ly assessed patients ' perceptions of fatigue and the impact of perceived fatigue on their everyday lives . OBJECTIVE The purpose of this study was to describe the prevalence , duration and severity of fatigue among patients with COPD and the impact of perceived fatigue on cognitive , physical and psychosocial functioning in comparison with controls . METHOD The Fatigue Impact Scale , including physical , psychosocial and cognitive dimension and structured questions about the frequency , duration , and severity of fatigue was mailed to 44 out patients with COPD and 88 r and omly selected age- and sex-matched controls . In total 36 patients and 37 controls completed the question naire . RESULTS Almost half of the patients ( 47.2 % ) , reported fatigue every day during the preceding month compared with 13.5 % of the control group ( P duration of fatigue was more than 6 hours in 52.7 % of the patients and 44.4 % reported that fatigue was either the worst or one of the worst symptoms they had , compared with 18.9 % ( P impact of fatigue on cognitive , physical and psychosocial functioning compared with the control group ( P < 0.001 ) . CONCLUSION These findings indicate that fatigue is a highly prevalent symptom , which impacts on patients ' functional condition and needs to be professionally assessed and managed", "OBJECTIVES To investigate the feasibility of an outdoor 6-minute walk test ( 6MWT ) as a measure of functional status among individuals with chronic obstructive pulmonary disease ( COPD ) , and to examine the relationship between performance on an indoor and an outdoor 6MWT . DESIGN An experimental , repeated- measures crossover design . Subjects were studied on 2 separate days in the same week . Two 6MWTs-one indoors and the other outdoors-were performed on each study day , with a rest in between . The test order was r and omly selected on the first day and reversed on the second day . Outdoor tests were performed on days of moderate weather conditions ( mean temperature + /- st and ard deviation , 21 degrees + /-3 degrees C ; mean wind speed , 15+/-7 km/h ; no precipitation ) and on a flat surface ( sidewalk ) . SETTING Outpatient rehabilitation program in Ontario . PARTICIPANTS Eighteen subjects with COPD ( 10 men , 8 women ; age , 70+/-8y ) , 5 using supplemental oxygen at rest ( forced expiratory volume in 1s , 1.0+/-0.3L ; 42%+/-8 % of predicted ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Distance walked in 6 minutes ( in meters ) , duration of rest ( in seconds ) , and change in rate of perceived dyspnea . RESULTS There was no significant effect of setting ( indoors vs outdoors ) on distance walked ( 394+/-86 m vs 398+/-84 m , P=0.4 ) , duration of rest ( 13+/-28s vs 9+/-20s , P=0.4 ) , or change in rate of perceived dyspnea ( 2.3+/-1.7 vs 2.3+/-2.0 , P=0.8 ) . Testing day had no significant effect on walk test performance ( all P>0.1 ) . CONCLUSIONS The results indicate that the 6MWT performed outdoors within reasonable climatic parameters may be reflective of 6MWT performance indoors", "UK guidelines for domiciliary oxygen have suggested the six-minute walk test or shuttle walk tests as suitable functional measures for the clinical assessment of ambulatory oxygen ( AO ) . To date , there is limited evidence that would support the use of shuttle walk tests as assessment tools for AO . The endurance shuttle walk test ( ESWT ) is used increasingly as an assessment tool within pulmonary rehabilitation ( PR ) but its potential as an investigative test for AO has not been explored . Using the same test for both PR and AO assessment is appealing since it would improve efficiency and act to st and ardise outcome measures in this patient population . The aim of this study was to examine the responsiveness and repeatability of the ESWT to AO and to compare the response with that of the six-minute walk test ( 6MWT ) . Twenty-three patients with chronic obstructive pulmonary disease ( COPD ) performed , in r and om order , the ESWT and the 6MWT on air and whilst breathing AO . Oxygen saturation and Borg ratings of breathlessness and perceived exertion were recorded . On a third day , eleven patients repeated the ESWT with AO in order to measure repeatability . There was a significantly greater change in the ESWT with oxygen than the change recorded from the 6MWT ( 66 [ 91 ] vs 6 [ 28 ] m respectively ; P difference ( 95 % CI ) between distances walked on the ESWT with AO was 0.91 ( -47 , 49 ) m. The ESWT was more responsive than the 6MWT for detecting improvements in walking endurance whilst breathing AO", "OBJECTIVES To assess the changes in physical activity in subjects with chronic obstructive pulmonary disease over 6months after pulmonary rehabilitation . DESIGN Prospect i ve , observational study . Activity was measured over 2-day periods at the end of rehabilitation , and repeated every 6weeks for 6months using the ActivPAL uni-axial accelerometer . These results were compared with the shuttle walking test ( SWT ) and the St. George 's Respiratory Disease Question naire ( SGRDQ ) . SETTING UK community hospital . PARTICIPANTS Adults completing a community rehabilitation programme . MAIN OUTCOME MEASURE Time spent st and ing and mobilising ( ' uptime ' ) . RESULTS Of 34 subjects recruited , 28 completed the 6-month study period ( mean age 69years , mean forced expiratory volume in 1second 1.3l ) . Participants wore the monitor for 13.8 to 14.2hours/day . At baseline ( post-rehabilitation ) , participants spent 1.7 [ st and ard deviation ( SD ) 1.3]hours/day walking and 3.5 ( SD 2.6)hours/day st and ing . Taking the group as a whole , mean uptime decreased marginally by 13.6minutes after 24weeks compared with baseline , with significant individual variability . In all but one subject who showed decreased activity , this was apparent after 6weeks . There were no significant changes in the mean SWT or SGRDQ . Significant associations between total uptime and the SWT were found , but coefficients were weak . It was not possible to predict individual responses from baseline data . CONCLUSION The accelerometer provides useful supplementary data in patients completing rehabilitation programmes , and the results reveal wide variation . The weak associations between activity data and the SWT suggest that monitors provide additional information . More work is required to determine the factors associated with early deterioration in activity in order to design appropriate interventions", "BACKGROUND Generally , the use of a rollator improves mobility in patients with COPD . Nevertheless , not all patients benefit from its use , and many patients feel embarrassed about using it . Therefore , other walking aids are worthwhile to consider . We compared the direct effects of a \" new \" ambulation aid ( a modern draisine ) with the effects of a rollator on 6-min walk distance ( 6MWD ) in patients with COPD . METHODS Twenty-one patients with COPD performed two 6-min walk tests ( 6MWTs ) during prerehabilitation assessment ( best 6MWD : 369 ± 88 m ) . Additionally , two extra 6MWTs were performed on two consecutive days in r and om order : one time with a rollator and one time with a modern draisine . Walking pattern ( n = 21 ) was determined using an accelerometer , and metabolic requirements ( n = 10 ) were assessed using a mobile oxycon . RESULTS Walking with the modern draisine result ed in a higher 6MWD compared with walking with the rollator ( 466 ± 189 m vs 383 ± 85 m ) . Moreover , patients had fewer strides ( 245 ± 61 vs 300 ± 49 ) and a greater stride length ( 1.89 ± 0.73 m vs 1.27 ± 0.14 m ) using the modern draisine compared with the rollator ( all P ≤ .001 ) . Oxygen uptake , ventilation , heart rate , oxygen saturation , and Borg symptom scores were comparable between both walking aids . Ten percent of the patients felt embarrassed using the modern draisine compared with 19 % for the rollator , and a significantly smaller proportion of patients would use the modern draisine in daily life . CONCLUSIONS The mean difference in 6MWD between a modern draisine and a rollator seems clinical ly relevant , with the same metabolic requirements and symptom Borg scores . Therefore , this \" new \" ambulation aid could be a good alternative to the rollator to improve functional exercise performance in patients with COPD . TRIAL REGISTRY The Netherl and s National Trial Registry ; No. : NTR1542 ; URL : www.trialregister.nl" ]	41189546-06ff-11f0-808a-c43d1ab1c353
INTRODUCTION Teeth requiring endodontic treatment commonly have compromised a coronal tooth structure that often requires the use of an intraradicular post to retain the coronal restoration . Although usually successful , catastrophic failures requiring extraction have been reported in the literature . The aim of this systematic review was to analyze clinical trials and cohort studies that evaluated the incidence rate of root fractures in post-retained restorations . The hypothesis was that the incidence rate related to the use of metal posts was higher than that of fiber posts . METHODS A MEDLINE search for clinical studies reporting the incidence of root fractures of restorations retained with fiber posts or metal posts of endodontically treated teeth with a more than 5-year follow-up was conducted from inception to January 2014 . Seven r and omized clinical trials and 7 cohort studies were included . RESULTS The pooled survival rate was 90 % ( 95 % confidence interval , 85.5 - 93.3 ) for metal-based posts and 83.9 % ( 95 % confidence interval , 67.6 - 92.8 ) for fiber-reinforced posts . The overall incidence rate of root fractures ( catastrophic failures ) was similar between metal and fiber posts . Prefabricated metal posts and carbon fiber posts had a 2-fold increase in the incidence rate of root fractures compared with cast metal posts and glass fiber posts , respectively . CONCLUSIONS The results of this study did not show significant differences for root fracture incidence between metal- and fiber posts . However , the studies included in this review presented a high risk of bias , and further well- design ed clinical studies are required to confirm these findings	[ "This study reports a prospect i ve clinical trial comparing a carbon fibre reinforced carbon ( CFRC ) endodontic post with a conventional prefabricated post . Twenty-seven single rooted maxillary anterior teeth in 18 patients ( nine males and nine females ; age range 18 - 60 years ) were restored either with a CFRC post or a wrought precious alloy control . Cast type III gold alloy cores were used in conjunction with both post groups . The CRFC posts ( n = 16 ) were cemented with a composite luting agent and the conventional posts ( control ) were cemented with zinc phosphate . Four failures were recorded in the CFRC post group at 24 , 29 , 56 and 87 months , compared with one failure in the control group at 84 months . These results suggest that post-retained crowns utilizing a CFRC material and a composite resin luting agent do not perform as well as conventional wrought precious alloy posts", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "OBJECTIVES This retrospective study investigated the clinical effectiveness over up to 8 years of parallel-sided and of tapered glass-fiber posts , in combination with either hybrid composite or dual-cure composite resin core material , in endodontically treated , maxillary anterior teeth covered with full-ceramic crowns . METHODS The study population comprised 192 patients and 526 endodontically treated teeth , with various degrees of hard-tissue loss , restored by the post- and -core technique . Four groups were defined based on post shape and core build-up material s , and within each group post- and -core restorations were assigned r and omly with respect to root morphology . Inclusion criteria were symptom-free endodontic therapy , root-canal treatment with a minimum apical seal of 4 mm , application of rubber dam , need for post- and -core complex because of coronal tooth loss , and tooth with at least one residual coronal wall . Survival rate of the post- and -core restorations was determined using Kaplan-Meier statistical analysis . RESULTS The restorations were examined clinical ly and radiologically ; mean observation period was 5.3 years . The overall survival rate of glass-fiber post- and -core restorations was 98.5 % . The survival rate for parallel-sided posts was 98.6 % and for tapered posts was 96.8 % . Survival rates for core build-up material s were 100 % for dual-cure composite and 96.8 % for hybrid light-cure composite . CONCLUSIONS For both glass-fiber post design s and for both core build-up material s , clinical performance was satisfactory . Survival was higher for teeth retaining four and three coronal walls", "PURPOSE In the present prospect i ve study , four different post- and -core systems were evaluated over a period of up to 10 years . MATERIAL S AND METHODS Fifty endodontically treated teeth in 31 patients were r and omized to one of four groups for post- and -core placement : Group 1 received conventional tapered cast posts and cores ( n = 14 ) ; group 2 received ParaPost system prefabricated gold posts with cast cores ( n = 13 ) ; group 3 received ParaPost system cast posts and cores ( n = 13 ) ; and group 4 received Radix-Anchor posts ( n = 10 ) . Clinical and radiologic evaluations were made . RESULTS One post and core in group 2 was functioning well 58 months after placement when the patient died . No posts and cores in groups 1 or 2 had been lost or had any complications , one in group 3 had been lost because of a root fracture after 108 months , and two in group 4 had been lost after 54 and 88 months , respectively , because of loss of retention . The final treatment result for 46 of the 49 remaining posts ( 30 patients ) was successful . The overall failure rate was 6 % . There were no statistically significant differences between the four groups . CONCLUSION If recommended procedures are strictly followed , posts and cores can serve as abutments for fixed single crowns with satisfactory long-term results", "PURPOSE This controlled clinical trial aim ed to compare the 3-year outcomes of glass fiber posts and composite cores with gold alloy-based posts and cores for the restoration of endodontically treated teeth . MATERIAL S AND METHODS One hundred forty-four patients in need of 205 restorations on endodontically treated teeth were selected and followed for 7 to 37 months ( mean : 21 ± 9 months ) . The teeth were primarily stratified based on the remaining tissue available to restore the tooth core with or without a post . Then , r and omization allocated the teeth to either test group 1 ( prefabricated glass fiber posts ) , test group 2 ( custom-made glass fiber posts ) , or test group 3 ( composite cores without posts ) . The control group consisted of gold alloy-based posts and cores . All posts/cores were covered with all-ceramic single crowns . Failures were either absolute , such as root fractures or irreparable fractures of the post/core , or relative , such as loss of post retention or reparable fractures of the core . Success and survival probability lifetime curves , corrected for clustering , were drawn for the entire data set . RESULTS The recall rate at 3 years was 97.1 % . Absolute failures consisted of two root fractures and one endodontic failure , while relative failures included three instances of retention loss of the post/core and one post fracture . Because of the low number of events , no statistical tests were performed . The success and survival probabilities over all groups together at 3 years amounted to 91.7 % and 97.2 % , respectively . CONCLUSIONS After being followed for up to 3 years , both cast gold and composite post and core systems performed well clinical ly . Longer follow-up times are needed to detect possible significant differences . Int J Prosthodont 2011;24:363 - 372", "Prospect i ve clinical studies comparing the results of different types of restorations of endodontically treated teeth are lacking . This study compared the clinical success rate of endodontically treated premolars restored with fiber posts and direct composite to the restorations of premolars using amalgam . Premolars with Class II carious lesions were selected and r and omly assigned to one of two experimental groups : ( 1 ) restoration with amalgam or ( 2 ) restoration with fiber posts and composite . One hundred and nine teeth were included in Group 1 and 110 in Group 2 . Patients were recalled after 1 , 3 and 5 years . No statistically significant difference was found between the proportion of failed teeth in the two experimental groups . Significant differences were observed between the proportion of root fractures ( p=0.029 ) and caries ( p=0.047 ) , with more root fractures and less caries observed in the teeth restored with amalgam at the five-year recall . Within the limits of this study , it can be concluded that restorations with fiber posts and composite were found to be more effective than amalgam in preventing root fractures but less effective in preventing secondary caries", "INTRODUCTION This is the first clinical long-term pilot study that tested the biomimetic concept of using more flexible , dentine-like ( low Young modulus ) glass fiber-reinforced epoxy resin posts ( GFREPs ) compared with rather rigid , stiff ( higher Young modulus ) titanium posts ( TPs ) in order to improve the survival rate of severely damaged endodontically treated teeth . METHODS Ninety-one subjects in need of postendodontic restorations in teeth with 2 or less remaining cavity walls were r and omly assigned to receive either a tapered TP ( n = 46 ) or a tapered GFREP ( n = 45 ) . The posts were adhesively luted using self-adhesive resin cement . The composite core build-ups were prepared ensuring a circumferential 2-mm ferrule . The primary endpoint was a loss of restoration for any reason . To study group differences , the log-rank test was calculated ( P failed ( ie , 4 GFREPs and 3 TPs ) . The failure modes were as follows : GFREP : root fracture ( n = 3 ) , core fracture ( n = 1 ) and TP : endodontic failure ( n = 3 ) . No statistical difference was found between the survival rates ( GFREPs = 90.2 % , TPs = 93.5 % , P = .642 ) . The probability of no failure was comparable for both post material s ( risk ratio ; 95 % confidence interval , 0.965 - 0.851/1.095 ) . CONCLUSIONS When using self-adhesive luted prefabricated posts in severely destroyed abutment teeth with 2 or less cavity walls and a 2-mm ferrule , postendodontic restorations achieved high long-term survival rates irrespective of the post material used ( ie , glass fiber vs titanium )" ]	41189582-06ff-11f0-808a-c43d1ab1c353
Background Significant , sustained weight loss through conventional , non-surgical interventions is often unattainable for people with severe obesity ( e.g. BMI ≥40 or ≥35 kg/m2 with co-morbidities ) . Bariatric surgery is effective in treating severe obesity , but surgery alone without additional behaviour change management may not result in optimum long-term weight loss and maintenance . This systematic review and meta- analysis of r and omised controlled trials evaluated the effectiveness of lifestyle interventions before and /or after bariatric surgery . Methods MEDLINE , Embase , Cochrane Central Register of Controlled Trials and clinical trials registers were search ed for eligible studies . Key journals were h and search ed . Last search date was on December 2014 . Eligible interventions had the explicit aim of changing behaviour related to diet and /or physical activity , starting within 12 months of surgery , either pre- or post-operatively , and with at least 6 months ’ follow-up . The primary outcome was weight change ; secondary outcomes included surgical complications , quality of life and changes in co-morbidities . R and om effect meta-analyses were undertaken . Study quality was assessed with the Cochrane Collaboration ’s risk of bias tool . Results Eleven trials met the inclusion criteria . Behavioural interventions appear to improve weight loss at 12 months after bariatric surgery . Secondary outcome data were lacking and weight outcomes were reported inconsistently . Overall , the method ological quality of the identified trials was low . Conclusions The strength of evidence is limited by the relatively small number of trials identified and by their low method ological quality and short follow-up duration . Well- design ed r and omised controlled trials ( RCTs ) with long-term follow-up are required	[ "BACKGROUND Bariatric surgery is a powerful treatment of severe obesity . During the past several years , a greater appreciation for the need for multidisciplinary care to optimize outcomes has developed , and a number of studies have been started to examine the role of postoperative interventions used in combination with surgery . The purpose of the present study was to investigate the hypothesis that the provision of postoperative dietary counseling , delivered by a registered dietitian , would lead to greater weight loss and more positive improvements in dietary intake and eating behavior compared with st and ard postoperative care . The study was performed at an academic medical center . METHODS Eighty-four individuals who underwent bariatric surgery were r and omly assigned to receive either dietary counseling or st and ard postoperative care for the first 4 months after surgery . The participants completed measures of macronutrient intake and eating behavior at baseline and 2 , 4 , 6 , 12 , 18 , and 24 months after surgery . RESULTS The patients who received dietary counseling achieved greater weight loss than those who received st and ard postoperative care that did not involve this counseling , although this difference did not reach statistical significance . Patients in the dietary counseling arm did report significant changes in several eating behaviors believed to be important to successful long-term weight maintenance . CONCLUSION The results of our pilot study provide some support for the efficacy of early postoperative dietary counseling to improve outcomes after bariatric surgery", "BACKGROUND Many comprehensive bariatric surgery programs have implemented preoperative behavioral interventions for patients presenting with problematic eating behaviors in an effort to enhance postoperative weight loss and improve psychosocial adjustment . However , it is unknown whether these interventions are best delivered pre- or postoperatively . The purpose of this study was to determine when bariatric surgery patients are most receptive to a behavioral intervention , before or after surgery . METHODS A total of 32 pre- and postoperative patients were referred to a 10-week intervention design ed to reduce eating behaviors associated with postoperative weight gain ( e.g. , loss of control while eating , grazing ) . The sample was 78.1 % female and 84.4 % white , with an average age of 49.43 + /- 9.13 years and a body mass index of 44.22 + /- 6.48 kg/m(2 ) . Of the 32 patients , 21 were referred preoperatively and 11 were referred postoperatively ( 5.63 + /- 2.91 months after surgery ) . These patients were tracked prospect ively to determine whether pre- or postoperative patients were more likely to attend and complete the behavioral intervention . RESULTS Compared with the preoperative patients , the postoperative patients were more likely to follow-up with their referral and initiate treatment [ chi(2)(1 ) = 10.06 , P = .002 ] . Of the postoperative patients , 100 % attended the first intervention session compared with only 43 % of preoperative patients . The postoperative patients also attended more intervention sessions [ t(18 ) = 2.51 , P = .02 ] and were more likely to complete the intervention [ chi(2)(1 ) = 7.21 , P = .007 ] . Only 14 % of the preoperative referral patients completed the program compared with 91 % of the postoperative patients . CONCLUSION Comprehensive bariatric surgery programs ought to consider balancing the needs of the preoperative patients presenting with maladaptive eating behavior with the likelihood of them participating in a behavioral intervention before surgery", "Background Many insurance payors m and ate that bariatric surgery c and i date s undergo a medically supervised weight management ( MSWM ) program as a prerequisite for surgery . However , there is little evidence to support this requirement . We evaluated in a r and omized controlled trial the hypothesis that participation in a MSWM program does not predict outcomes after laparoscopic adjustable gastric b and ing ( LAGB ) in a publicly insured population . Methods This pilot r and omized trial was conducted in a large academic urban public hospital . Patients who met NIH consensus criteria for bariatric surgery and whose insurance did not require a m and atory 6-month MSWM program were r and omized to a MSWM program with monthly visits over 6 months ( individual or group ) or usual care for 6 months and then followed for bariatric surgery outcomes postoperatively . Demographics , weight , and patient behavior scores , including patient adherence , eating behavior , patient activation , and physical activity , were collected at baseline and at 6 months ( immediately preoperatively and postoperatively ) . Results A total of 55 patients were enrolled in the study with complete follow-up on 23 patients . Participants r and omized to a MSWM program attended an average of 2 sessions preoperatively . The majority of participants were female and non-Caucasian , mean age was 46 years , average income was less than $ 20,000/year , and most had Medicaid as their primary insurer , consistent with the demographics of the hospital ’s bariatric surgery program . Data analysis included both intention-to-treat and completers ’ analyses . No significant differences in weight loss and most patient behaviors were found between the two groups postoperatively , suggesting that participation in a MSWM program did not improve weight loss outcomes for LAGB . Participation in a MSWM program did appear to have a positive effect on physical activity postoperatively . Conclusion MSWM does not appear to confer additional benefit as compared to the st and ard preoperative bariatric surgery protocol in terms of weight loss and most behavioral outcomes after LAGB in our patient population", "BACKGROUND Roux-en-Y gastric bypass surgery is the leading surgical treatment of morbid obesity in the United States . The role of preoperative weight loss in gastric bypass surgery remains controversial . We performed a prospect i ve r and omized trial to determine whether preoperative weight loss results in better outcomes after laparoscopic gastric bypass . METHODS A total of 100 patients undergoing laparoscopic gastric bypass surgery from May 2004 to October 2005 were r and omized preoperatively to either a weight loss group with a 10 % weight loss requirement or a group that had no weight loss requirements . The patients were followed prospect ively . The variables analyzed included perioperative complications , operative time , postoperative weight loss , and resolution of co-morbidities . RESULTS Data were available for 26 patients in the weight loss group and 35 in the nonweight loss group . The 2 groups had similar preoperative characteristics , conversion and complication rates , and resolution of co-morbidities . The initial body mass index was 48.7 kg/m(2 ) and 49.3 kg/m(2 ) for the weight loss group and nonweight loss group , respectively ( P = NS ) . The preoperative body mass index was 44.5 kg/m(2 ) and 50.7 kg/m(2 ) for the weight loss group and nonweight loss group , respectively ( P = 0.0027 ) . The operative time was 220.2 and 257.6 minutes for the 2 groups ( P = 0.0084 ) . The percentage of excess weight loss at 3 and 6 months for the weight loss group and nonweight loss group was 44.1 % and 33.1 % ( P = 0.0267 ) and 53.9 % and 50.9 % ( P = NS ) , respectively . The interval to surgery from the initial consultation was 5.4 months and 5.2 months for the 2 groups ( P = NS ) . CONCLUSIONS Preoperative weight loss before laparoscopic Roux-en-Y gastric bypass was associated with a decrease in the operating room time and an improved percentage of excess weight loss in the short term . Preoperative weight loss , however , did not affect the major complication or conversion rates , and its long-term effects were not apparent through this study . Also , preoperative weight loss did not have any bearing on the resolution of co-morbidities", "Background A certain weight gain occurs after obesity surgery compared to the lower weight usually observed between 18 and 24 months postsurgery . The objective of this study was to evaluate weight regain in patients su bmi tted to gastric bypass over a 5-year follow-up period . Material s and Methods A longitudinal prospect i ve study was conducted on 782 obese patients of both genders . Only patients with at least 2 years of surgery were included . The percentage of excess body mass index ( BMI ) loss at 24 , 36 , 48 , and 60 months postsurgery was compared to the measurements obtained at 18 months after surgery . Surgical therapeutic failure was also evaluated . Results Percent excess BMI loss was significant up to 18 months postsurgery ( p Percent BMI loss was no longer significant after 24 months , and weight regain became significant within 48 months after surgery ( p weight regain , a mean 8 % increase was observed within 60 months compared to the lowest weight obtained at 18 months after surgery . The percentage of surgical failure was higher in the superobese group at all times studied , reaching 18.8 % at 48 months after surgery . Conclusion Weight regain was observed within 24 months after surgery in approximately 50 % of patients . Both weight regain and surgical failure were higher in the superobese group . Studies in regard to metabolic and hormonal mechanisms underlying weight regain might eluci date the causes of this finding", "BACKGROUND Roux-en-Y gastric bypass ( RYGB ) surgery causes profound weight loss and improves insulin sensitivity ( S(I ) ) in obese patients . Regular exercise can also improve S(I ) in obese individuals ; however , it is unknown whether exercise and RYGB surgery-induced weight loss would additively improve S(I ) and other cardiometabolic factors . METHODS We conducted a single-blind , prospect i ve , r and omized trial with 128 men and women who recently underwent RYGB surgery ( within 1 - 3 months ) . Participants were r and omized to either a 6-month semi-supervised moderate exercise protocol ( EX , n = 66 ) or a health education control ( CON ; n = 62 ) intervention . Main outcomes measured included S(I ) and glucose effectiveness ( S(G ) ) , which were determined from an intravenous glucose tolerance test and minimal modeling . Secondary outcomes measured were cardiorespiratory fitness ( VO2 peak ) and body composition . Data were analyzed using an intention-to-treat ( ITT ) and per- protocol ( PP ) approach to assess the efficacy of the exercise intervention ( > 120 min of exercise/week ) . RESULTS 119 ( 93 % ) participants completed the interventions , 95 % for CON and 91 % for EX . There was a significant decrease in body weight and fat mass for both groups ( P S(I ) improved in both groups following the intervention ( ITT : CON vs. EX ; + 1.64 vs. + 2.24 min⁻¹/μU/ml , P = 0.18 for Δ , P additive S(I ) improvement ( PP : CON vs. EX ; + 1.57 vs. + 2.69 min⁻¹/μU/ml , P = 0.019 ) above that of surgery . Exercise also improved S(G ) ( ITT : CON vs. EX ; + 0.0023 vs. + 0.0063 min⁻¹ , P = 0.009 ) compared with the CON group . Exercise improved cardiorespiratory fitness ( VO2 peak ) compared with the CON group . CONCLUSION Moderate exercise following RYGB surgery provides additional improvements in S(I ) , S(G ) , and cardiorespiratory fitness compared with a sedentary lifestyle during similar weight loss . TRIAL REGISTRATION clinical trials.gov identifier : NCT00692367 . FUNDING This study was funded by the NIH/National Institute of Diabetes and Digestive and Kidney Diseases ( R01 DK078192 ) and an NIH/National Center for Research Re sources / Clinical and Translational Science Award ( UL1 RR024153 )", "IMPORTANCE Short-term studies show that bariatric surgery causes remission of diabetes . The long-term outcomes for remission and diabetes-related complications are not known . OBJECTIVES To determine the long-term diabetes remission rates and the cumulative incidence of microvascular and macrovascular diabetes complications after bariatric surgery . DESIGN , SETTING , AND PARTICIPANTS The Swedish Obese Subjects ( SOS ) is a prospect i ve matched cohort study conducted at 25 surgical departments and 480 primary health care centers in Sweden . Of patients recruited between September 1 , 1987 , and January 31 , 2001 , 260 of 2037 control patients and 343 of 2010 surgery patients had type 2 diabetes at baseline . For the current analysis , diabetes status was determined at SOS health examinations until May 22 , 2013 . Information on diabetes complications was obtained from national health registers until December 31 , 2012 . Participation rates at the 2- , 10- , and 15-year examinations were 81 % , 58 % , and 41 % in the control group and 90 % , 76 % , and 47 % in the surgery group . For diabetes assessment , the median follow-up time was 10 years ( interquartile range [ IQR ] , 2 - 15 ) and 10 years ( IQR , 10 - 15 ) in the control and surgery groups , respectively . For diabetes complications , the median follow-up time was 17.6 years ( IQR , 14.2 - 19.8 ) and 18.1 years ( IQR , 15.2 - 21.1 ) in the control and surgery groups , respectively . INTERVENTIONS Adjustable or nonadjustable b and ing ( n = 61 ) , vertical b and ed gastroplasty ( n = 227 ) , or gastric bypass ( n = 55 ) procedures were performed in the surgery group , and usual obesity and diabetes care was provided to the control group . MAIN OUTCOMES AND MEASURES Diabetes remission , relapse , and diabetes complications . Remission was defined as blood glucose mg/dL and no diabetes medication . RESULTS The diabetes remission rate 2 years after surgery was 16.4 % ( 95 % CI , 11.7%-22.2 % ; 34/207 ) for control patients and 72.3 % ( 95 % CI , 66.9%-77.2 % ; 219/303 ) for bariatric surgery patients ( odds ratio [ OR ] , 13.3 ; 95 % CI , 8.5 - 20.7 ; P the diabetes remission rates decreased to 6.5 % ( 4/62 ) for control patients and to 30.4 % ( 35/115 ) for bariatric surgery patients ( OR , 6.3 ; 95 % CI , 2.1 - 18.9 ; P the cumulative incidence of microvascular complications was 41.8 per 1000 person-years ( 95 % CI , 35.3 - 49.5 ) for control patients and 20.6 per 1000 person-years ( 95 % CI , 17.0 - 24.9 ) in the surgery group ( hazard ratio [ HR ] , 0.44 ; 95 % CI , 0.34 - 0.56 ; P Macrovascular complications were observed in 44.2 per 1000 person-years ( 95 % CI , 37.5 - 52.1 ) in control patients and 31.7 per 1000 person-years ( 95 % CI , 27.0 - 37.2 ) for the surgical group ( HR , 0.68 ; 95 % CI , 0.54 - 0.85 ; P = .001 ) . CONCLUSIONS AND RELEVANCE In this very long-term follow-up observational study of obese patients with type 2 diabetes , bariatric surgery was associated with more frequent diabetes remission and fewer complications than usual care . These findings require confirmation in r and omized trials . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01479452", "The present study was design ed to evaluate the 3 year effects of a lifestyle intervention on weight loss and maintenance , dietary , and physical activity habits and eating behavior of patients following vertical b and ed gastroplasty ( VBG ) . Thirty severely obese female volunteers were included in the study and they were r and omly assigned to one of two intervention groups : usual care ( UC ) or lifestyle intervention ( LS ) group . Patients were followed for 3 years postoperatively . Outcome measures included weight loss , dietary habits , physical activity level ( PAL ) , and eating behavior changes . Weight was significantly lower in the LS group after 12 months ( 84.4 + /- 3.9 kg vs. 98.4 + /- 4.4 kg , P PAL and TV viewing . With regard to eating behavior , the LS group scored significantly better in total Dutch Eating Behavior Question naire ( DEBQ ) , Restraint Eating and External Eating scales at all postoperative time points . Similarly , significant differences were found between the two groups in dietary intake . These findings outline the importance of lifestyle intervention on weight loss and maintenance following bariatric surgery . The favorable effects of lifestyle intervention may be through adoption of healthier eating behaviors and increased physical activity", "Background The purpose of the present study is to evaluate the impact of a health psychology-led bariatric rehabilitation service ( BRS ) on patient weight loss following bariatric surgery at 1 year . Methods A single-site open-r and omised parallel group control trial based at St. Richard ’s Hospital in Chichester in the UK . Patients ( n = 162 ) were recruited immediately prior to Roux-en-Y gastric bypass and r and omly allocated to receive either treatment as usual ( n = 80 ) or the BRS ( n = 82 ) . The BRS involved three 50-min one-to-one sessions with a health psychologist and provided information , support and mentoring pre and post surgery addressing psychological issues such as dietary control , self esteem , coping and emotional eating . Weight loss was assessed at 1 year . The key outcome variable was BMI and change in BMI . Results Follow-up weight was available for 145 patients . Intention-to-treat analysis ( n = 162 ) using last measured weights showed that mean change in BMI by 1 year post surgery was −16.49 . There was no significant difference between the two groups ( control group = −16.37 , 95 % CI = 15.15–17.57 ; intervention = −16.6 , 95 % CI = 15.42–17.81 ; ηp2 = 0.001 ) . Similarly , explanatory analysis ( n = 145 ) showed a mean change in BMI of −17.17 . The difference between the two groups was not significant ( control group = −16.9 , 95 % CI = 15.78–18.18 ; intervention = −17.35 , 95 % CI = 18.5–16.16 ; ηp2 = 0.001 ) . Conclusions Psychological support pre and post bariatric surgery had no impact on weight loss as measured by BMI and change in BMI by 1 year . It is argued that psychological support should be targeted to patients who start to demonstrate weight regain at a later stage . Trial registration : Clinical Trials.gov NCT01264120", "Background Bariatric surgery is currently the most effective form of obesity management for those whose BMI is greater than 40 ( or 35 with co morbidities ) . A minority of patients , however , either do not show the desired loss of excess weight or show weight regain by follow up . Research highlights some of the reasons for this variability , most of which centres on the absence of any psychological support with patients describing how although surgery fixes their body , psychological issues relating to dietary control , self esteem , coping and emotional eating remain neglected . The present study aims to evaluate the impact of a health psychology led bariatric rehabilitation service ( BRS ) on patient health outcomes . The bariatric rehabilitation service will provide information , support and mentoring pre and post surgery and will address psychological issues such as dietary control , self esteem , coping and emotional eating . The package reflects the rehabilitation services now common place for patients post heart attack and stroke which have been shown to improve patient health outcomes . Methods / Design The study is a r and omised control trial and patients will be allocated to receive either usual care or the bariatric rehabilitation service pre and post bariatric surgery . Follow up measures of weight loss and psychological issues will be taken at baseline ( 2 weeks preoperatively ) , 3 , 6 and 12 months postoperatively . The contents of the bariatric service and the follow up measures are based on previous pilot work and have been developed further by the research team working closely with two patient support groups ( BOSPA & WLSinfo ) . This study will take place in St Richard 's Hospital in Chichester in the UK . Discussion It is predicted that a bariatric rehabilitation service will improve weight loss following surgery and will also facilitate changes in other psychological variables such as quality of life , dietary control , self esteem , coping and emotional eating . This also has cost implication s for the NHS and other healthcare providers as improved effectiveness of bariatric surgery reduces the health costs of obese patients in the longer term . Trial registration Clinical Trials.gov NCT01264120", "BACKGROUND Laparoscopic gastric bypass has become the st and ard surgical treatment for severe obesity in the United States . Less clear is what diet should be followed by these patients after surgery to maximize their weight loss . METHODS Patients undergoing laparoscopic gastric bypass procedures for morbid obesity were r and omly assigned to either a low-fat control diet based on American Heart Association recommendations or a low-carbohydrate , high-protein diet based on the South Beach Diet . One-on-one diet counseling with a bariatric nutritionist was provided preoperatively , postoperatively while in the hospital , and at postoperative clinic visits during the 12-month follow-up period . Investigators were blinded to diet assignment . Body composition including Body Mass Index ( BMI ) was recorded preoperatively and during postoperative visits at 3 , 6 , and 12 months . RESULTS Thirty-two patients were included in the analysis with 13 control and 19 low-carbohydrate , high-protein subjects . No demographic or clinical preoperative variables , including preoperative BMI , showed statistical differences between the two groups . Both groups demonstrated significant yet similar weight loss both by reduction in BMI ( at 12 months , low fat diet , -14.0 + /- 5.5 % versus low carbohydrate , -17.0 + /- 4.5 % ; P = 0.15 ) and excess body weight lost ( at 12 months , low-fat diet , -60.3 + /- 15.3 % versus low carbohydrate , -59.6 + /- 13.0 % ; P = 0.96 ) . CONCLUSIONS Based on this limited prospect i ve study , no weight loss advantage is observed in substituting a low-carbohydrate , high-protein diet in place of a st and ard low-fat diet in patients who have undergone laparoscopic gastric bypass surgery", "OBJECTIVE To evaluate the effect of 2 post-bariatric support interventions on depressive symptoms of Hispanic Americans treated with gastric bypass for morbid or severe obesity . DESIGN / SETTING Prospect i ve r and omized , controlled trial conducted in a laparoscopic institution . PARTICIPANTS / INTERVENTIONS During the Phase 1 clinical trial ( from preoperative evaluation to 6 months after surgery ) , all participants received st and ard care . During Phase 2 ( 6 - 12 months after surgery ) , participants were r and omly assigned to receive either st and ard care ( n = 72 ) or comprehensive support ( n = 72 ) . Comprehensive group participants received 6 educational sessions focused on behavior change strategies and motivation with nutrition counseling . MAIN OUTCOME MEASURES Depression scores and weight change over time . ANALYSIS Independent sample s t tests and regression analysis assessed relationships among depression scores and excess weight loss . RESULTS Participants receiving behavioral-motivational intervention scored significantly lower on Beck 's Depression Inventory question naire scores than those receiving st and ard care . For those with depressive symptoms at r and omization , 24 % of participants who received the comprehensive intervention reported no depressive symptoms at 12 months after surgery , compared with 6 % of those who received st and ard care ( P depressive mood improvement was significantly and positively associated with excess weight loss and attendance at educational sessions ( P post-bariatric comprehensive behavioral-motivational nutrition education for decreasing risk for depression and improving weight loss", "Weight regain is a problem among many bariatric surgery patients . Whether a high-volume exercise program ( HVEP ) , a strategy to limit weight regain , is feasible in these patients is unknown . The feasibility of an HVEP in obese post-bariatric-surgery patients was determined by r and omizing 33 Roux-en-Y gastric bypass ( RYGB ) and gastric b and ing ( GB ) surgery patients with a mean BMI of 41 ± 6 kg/m2 to an HVEP or control group for 12 weeks . The HVEP group was instructed to expend ≥ 2,000 kcal/week in moderate-intensity exercise . All patients were counseled to limit energy intake . Treatment effect was assessed by repeated measures analysis . During the last 4 weeks of the study , 53 % of the HVEP group expended ≥ 2,000 kcal/week and 82 % expended ≥ 1,500 kcal/week . Step count , reported time spent and energy expended during moderate physical activity , maximal oxygen consumption relative to weight , and incremental area under the postpr and ial blood glucose curve were significantly improved over 12 weeks in the HVEP group compared to controls ( group-by-week effect : P = 0.009 - 0.03 ) . Both groups reported significant improvement in some quality -of-life scales . Changes in weight , energy and macronutrient intake , resting energy expenditure ( REE ) , fasting lipids and glucose , and fasting and postpr and ial insulin concentrations were not different between the two groups . HVEP is feasible in about 50 % of the patients and enhances physical fitness and reduces postpr and ial blood glucose in bariatric surgery patients", "CONTEXT Extreme obesity is associated with health and cardiovascular disease risks . Although gastric bypass surgery induces rapid weight loss and ameliorates many of these risks in the short term , long-term outcomes are uncertain . OBJECTIVE To examine the association of Roux-en-Y gastric bypass ( RYGB ) surgery with weight loss , diabetes mellitus , and other health risks 6 years after surgery . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve Utah-based study conducted between July 2000 and June 2011 of 1156 severely obese ( body mass index [ BMI ] ≥ 35 ) participants aged 18 to 72 years ( 82 % women ; mean BMI , 45.9 ; 95 % CI , 31.2 - 60.6 ) who sought and received RYGB surgery ( n = 418 ) , sought but did not have surgery ( n = 417 ; control group 1 ) , or who were r and omly selected from a population -based sample not seeking weight loss surgery ( n = 321 ; control group 2 ) . MAIN OUTCOME MEASURES Weight loss , diabetes , hypertension , dyslipidemia , and health-related quality of life were compared between participants having RYGB surgery and control participants using propensity score adjustment . RESULTS Six years after surgery , patients who received RYGB surgery ( with 92.6 % follow-up ) lost 27.7 % ( 95 % CI , 26.6%-28.9 % ) of their initial body weight compared with 0.2 % ( 95 % CI , -1.1 % to 1.4 % ) gain in control group 1 and 0 % ( 95 % CI , -1.2 % to 1.2 % ) in control group 2 . Weight loss maintenance was superior in patients who received RYGB surgery , with 94 % ( 95 % CI , 92%-96 % ) and 76 % ( 95 % CI , 72%-81 % ) of patients receiving RYGB surgery maintaining at least 20 % weight loss 2 and 6 years after surgery , respectively . Diabetes remission rates 6 years after surgery were 62 % ( 95 % CI , 49%-75 % ) in the RYGB surgery group , 8 % ( 95 % CI , 0%-16 % ) in control group 1 , and 6 % ( 95 % CI , 0%-13 % ) in control group 2 , with remission odds ratios ( ORs ) of 16.5 ( 95 % CI , 4.7 - 57.6 ; P incidence of diabetes throughout the course of the study was reduced after RYGB surgery ( 2 % ; 95 % CI , 0%-4 % ; vs 17 % ; 95 % CI , 10%-24 % ; OR , 0.11 ; 95 % CI , 0.04 - 0.34 compared with control group 1 and 15 % ; 95 % CI , 9%-21 % ; OR , 0.21 ; 95 % CI , 0.06 - 0.67 compared with control group 2 ; both P bariatric surgery-related hospitalizations were 33 ( 7.9 % ) , 13 ( 3.9 % ) , and 6 ( 2.0 % ) for the RYGB surgery group and 2 control groups , respectively . CONCLUSION Among severely obese patients , compared with nonsurgical control patients , the use of RYGB surgery was associated with higher rates of diabetes remission and lower risk of cardiovascular and other health outcomes over 6 years", "BACKGROUND Weight loss is associated with short-term amelioration and prevention of metabolic and cardiovascular risk , but whether these benefits persist over time is unknown . METHODS The prospect i ve , controlled Swedish Obese Subjects Study involved obese subjects who underwent gastric surgery and contemporaneously matched , conventionally treated obese control subjects . We now report follow-up data for subjects ( mean age , 48 years ; mean body-mass index , 41 ) who had been enrolled for at least 2 years ( 4047 subjects ) or 10 years ( 1703 subjects ) before the analysis ( January 1 , 2004 ) . The follow-up rate for laboratory examinations was 86.6 percent at 2 years and 74.5 percent at 10 years . RESULTS After two years , the weight had increased by 0.1 percent in the control group and had decreased by 23.4 percent in the surgery group ( P weight had increased by 1.6 percent and decreased by 16.1 percent , respectively ( P Energy intake was lower and the proportion of physically active subjects higher in the surgery group than in the control group throughout the observation period . Two- and 10-year rates of recovery from diabetes , hypertriglyceridemia , low levels of high-density lipoprotein cholesterol , hypertension , and hyperuricemia were more favorable in the surgery group than in the control group , whereas recovery from hypercholesterolemia did not differ between the groups . The surgery group had lower 2- and 10-year incidence rates of diabetes , hypertriglyceridemia , and hyperuricemia than the control group ; differences between the groups in the incidence of hypercholesterolemia and hypertension were undetectable . CONCLUSIONS As compared with conventional therapy , bariatric surgery appears to be a viable option for the treatment of severe obesity , result ing in long-term weight loss , improved lifestyle , and , except for hypercholesterolemia , amelioration in risk factors that were elevated at baseline", "OBJECTIVE To assess if attendance to a preoperative counseling program improved weight loss or adherence to treatment guidelines in patients who underwent bariatric surgery . METHODS One-hundred-forty-one patients were included in the study . Sixty-nine percent chose to participate in the counseling groups . They were r and omized to a Treatment group and a Control group . Thirty-one percent chose not to participate in the counseling . However , they gave their consent to assessment before and after surgery ( Reference group ) . RESULTS One year after bariatric surgery , 88 % had a weight loss of ≥ 50 % EWL , 37 % reported more than 30 min of physical activity daily , 74 % had 5 - 7 meals daily , and 87 % took recommended vitamins . There were no differences in weight loss , eating habits , or physical exercise between the Treatment group , the Control group and the Reference group one year after surgery . CONCLUSION Preoperative group counseling did not increase treatment adherence to recommended life-style changes . PRACTICE IMPLICATION S In accordance with findings in the present study , it is not reasonable to offer a preoperative counseling program for all patients undergoing bariatric surgery . Further research should focus on developing and evaluating programs for postsurgical follow-up , and identifying patients that are in need for more comprehensive treatment programs", "Background In recent years , the p and emic explosion of obesity has led to the definition of a pre-eminent therapeutic role for bariatric surgery , confining physical activity to a success parameter of surgery rather than a primary prevention measure . The aim of this study is to evaluate the role for aerobic physical activity ( road running ) in strengthening the metabolic and psychosocial effects of bariatric surgery . Methods Ten patients who underwent gastric bypass for morbid obesity were su bmi tted to an intensive program of road running training , aim ed at completing a 10.5-km competition in September 2013 . Inclusion criteria included age ( were enrolled as a control group . During the training period , patients were su bmi tted to biometrical , sport performance , cardiopulmonary , metabolic , and psychiatric evaluations . Results Protocol adherence was 70 % ; no physical injury was registered among participants . More than weight loss ( BMI 29.3 to 27.1 ) , the runners experienced a redistribution of body mass with significant differences in fat percentage and waist/hip ratio . Participants had a significant running performance improvement and , differently from the controls , a significant amelioration of echocardiographic and cardiopulmonary parameters , predicting a reduction in cardiovascular risk . Psychiatric evaluation underlined a tendency to a reduction in anxiety , depression , and general psychopathology symptoms . Conclusions Road running seems to have an important supporting role in boosting bariatric surgery results . The utilization of monitored and regulated training programs represents a fundamental prerequisite to achieving satisfactory results and patient compliance", "OBJECTIVE To examine the impact of a pre-bariatric surgery physical activity intervention ( PAI ) , design ed to increase bout-related ( ≥10 min ) moderate to vigorous PA ( MVPA ) , on health-related quality of life ( HRQoL ) . METHODS Analyses included 75 adult participants ( 86.7 % female ; BMI = 45.0 ± 6.5 kg m(-2 ) ) who were r and omly assigned to 6 weeks of PAI ( n = 40 ) or st and ard pre-surgical care ( SC ; n = 35 ) . PAI received 6 individual weekly counseling sessions to increase walking exercise . Participants wore an objective PA monitor for 7 days and completed the SF-36 Health Survey at baseline and post-intervention to evaluate bout-related MVPA and HRQoL changes , respectively . RESULTS PAI increased bout-related MVPA from baseline to post-intervention ( 4.4 ± 5.5 to 21.0 ± 21.4 min day(-1 ) ) versus no change ( 7.9 ± 16.6 to 7.6 ± 11.5 min day(-1 ) ) for SC ( P = 0.001 ) . PAI reported greater improvements than SC on all SF-36 physical and mental scales ( P except role-emotional . In PAI , better baseline scores on the physical function and general health scales predicted greater bout-related MVPA increases ( P on the physical function , bodily pain , and general health scales ( P Increasing PA preoperatively improves physical and mental HRQoL in bariatric surgery c and i date s. Future studies should examine whether this effect improves surgical safety , weight loss outcomes , and postoperative", "BACKGROUND Although bariatric surgery is associated with significant overall weight loss , many patients experience suboptimal outcomes . Our objective was to document the preliminary efficacy of a behavioral intervention for bariatric surgery patients with relatively poor long-term weight loss and to explore the factors related to outcome at an academic medical center in the United States . METHODS Patients with a body mass index ( BMI ) ≥ 30 kg/m(2 ) who had undergone bariatric surgery ≥ 3 years before study entry and had The participants were r and omly assigned to a 6-month behavioral intervention or wait list control group . The assessment s were conducted at baseline ( before intervention ) and 6 months ( after intervention ) and 12 months ( 6-mo follow-up ) . RESULTS On average , the participants ( n = 36 ) had undergone surgery 6.6 years before study entry . The average age was 52.5 ± 7.1 years , and the BMI was 43.1 ± 6.2 kg/m(2 ) ; most participants were women ( 75 % ) and white ( 88.9 % ) . The intervention patients had a greater percentage of excess weight loss than did the wait list control group at 6 ( 6.6 % ± 3.4 % versus 1.6 % ± 3.1 % ) and 12 ( 5.8 % ± 3.5 % versus .9 % ± 3.2 % ) months . However , the differences were not significant and the results varied . The intervention patients with more depressive symptoms ( P = .005 ) and less weight regain before study entry ( P = .05 ) experienced a greater percentage of excess weight loss . CONCLUSION Behavioral intervention holds promise in optimizing long-term weight control after bariatric surgery . More research is needed on when to initiate the intervention and to identify which patients will benefit from this type of approach", "BACKGROUND As morbid obesity increasingly affects Hispanic Americans , the incidence of bariatric procedures among this population is rising . Despite this , prospect i ve research on the effects of comprehensive postoperative education-centered interventions on weight loss and physical activity focused on Hispanic Americans is lacking . OBJECTIVE To examine whether a comprehensive nutrition education and behavior modification intervention improves weight loss and physical activity in Hispanic Americans with obesity following Roux-en-Y gastric bypass surgery ( RYGB ) . METHODS A prospect i ve r and omized-controlled trial was conducted between November 2008 and April 2010 . At 6 months following RYGB , 144 Hispanic Americans with obesity were r and omly assigned to a comprehensive nutrition and lifestyle educational intervention ( n=72 ) or a noncomprehensive approach ( comparison group n=72 ) . Those in the comprehensive group received education sessions every other week for 6 weeks in small groups and frequent contact with a registered dietitian . Those in the comparison group received brief , printed healthy lifestyle guidelines . Patients were reassessed at 12 months following surgery . Main outcome measures were excess weight loss and physical activity changes over time . Statistical analyses used t test , ? ( 2 ) test , Wilcoxon signed rank , Mann-Whitney U test , and intent-to-treat analysis , significance P RESULTS Participants ( mean age 44.5 ± 13.5 years ) were mainly Cuban-born women ( 83.3 % ) . Mean preoperative excess weight and body mass index ( calculated as kg/m(2 ) ) were 72.20 ± 27.81 kg and 49.26 ± 9.06 , respectively . At 12 months following surgery , both groups lost weight significantly , but comprehensive group participants experienced greater excess weight loss ( 80 % vs 64 % from preoperative excess weight ; P and greater body mass index reduction ( 6.48 ± 4.37 vs 3.63 ± 3.41 ; P involved in physical activity ( + 14 min/wk vs ? 4 min/wk ; P participants . Mean protein intake was significantly lower in the comparison group than that in the comprehensive group ( P effective weight reduction in Hispanic Americans following RYGB", "BACKGROUND Historically , preoperative weight loss has been encouraged for patients undergoing gastric bypass surgery to decrease liver mass , technically facilitating the procedure . In an earlier prospect i ve r and omized trial investigating effects of preoperative weight loss on patients ' clinical outcomes , we reported no differences in postoperative complications or weight-loss profiles at 6-month followup . This article demonstrates results of the same study , with 1-year followup . STUDY DESIGN One hundred consecutive patients in an 18-month period preparing to undergo gastric bypass surgery at Stanford University Medical Center were selected . Fifty patients were r and omly assigned to lose 10 % or more of their excess body weight preoperatively , and 50 patients were assigned to no preoperative weight-loss requirements . After 1 year , patient demographics and data on postoperative complications , cure or improvement of comorbidities , and differences in weight-loss profiles were collected . RESULTS At 1 year , the 2 groups had similar preoperative demographics and body mass indexes ( BMI s ) . Patients in the weight-loss group , on average , lost 8.2 % of their excess body weight preoperatively compared with the nonweight-loss group , which gained 1.1 % ( p = 0.007 ) . After a year , the patients in both arms of the study showed no difference in weight , BMI , excess weight-loss , and number of remaining comorbidites . But when patients were divided according to those who had lost at least 5 % of their excess body weight preoperatively , the 1-year results for excess weight-loss , weight , and BMI were much lower for the weight-loss group . CONCLUSIONS Preoperative weight loss in patients undergoing gastric bypass surgery is safe and feasible . It should be encouraged , because it will markedly improve longterm weight loss", "Outcome reporting in bariatric surgery needs a core outcome set ( COS ) , an agreed minimum set of outcomes reported in all studies of a particular condition . The aim of this study was to summarize outcome reporting in bariatric surgery to inform the development of a COS . Outcomes reported in r and omized controlled trials ( RCTs ) and large non-r and omized studies identified by a systematic review were listed verbatim and categorized into domains , scrutinizing the frequency of outcome reporting and uniformity of definitions . Ninety studies ( 39 RCTs ) identified 1,088 separate outcomes , grouped into nine domains with most ( n = 920 , 85 % ) reported only once . The largest outcome domain was ' surgical complications ' , and overall , 42 % of outcomes corresponded to a theme of ' adverse events ' . Only a quarter of outcomes were defined , and where provided definitions , which were often contradictory . Percentage of excess weight loss was the main study outcome in 49 studies , but nearly 40 % of weight loss outcomes were heterogeneous , thus not comparable . Outcomes of diverse bariatric operations focus largely on adverse events . Reporting is inconsistent and ill-defined , limiting interpretation and comparison of published studies . Thus , we propose and are developing a COS for the surgical treatment of severe and complex obesity" ]	411895be-06ff-11f0-808a-c43d1ab1c353
Abstract Background : Although non-specific low back pain ( LBP ) is known to be multifactorial , studies from across the globe have documented their higher prevalence in nurses . This systematic review was conducted to ascertain whether this much-documented association constitutes a causal relationship , and whether there is a discernible threshold of exposures associated with this elevated risk . Methods : PRISMA guidelines were followed and st and ard critical appraisal tools were applied . The outcome of interest was non-specific LBP or back injury ; exposure was “ performing nursing duties . ” Applicable studies , published in English during 1980–2012 , were identified through data base search es , screened against preset inclusion /exclusion criteria . Ergonomic assessment s of nursing tasks were included along with epidemiological studies . Bradford Hill considerations for causation were utilized as a framework for discussing findings . Findings : Of 987 studies identified , 89 qualified for inclusion , comprising 21 longitudinal , 36 cross-sectional analytic , 23 descriptive biomechanical/ergonomic , and 9 review studies . Overall studies showed that nursing activities conferred increased risk for , and were associated with back disorders regardless of nursing technique , personal characteristics , and non-work-related factors . Patient h and ling appears to confer the highest risk , but other nursing duties are also associated with elevated risk , and confound dose – response assessment s related to patient h and ling alone . Associations were strong , consistent , temporally possible , plausible , coherent , and analogous to other exposure- outcomes , with risk estimates ranging from 1·2 to 5·5 depending on definitions . A threshold of nursing activities below which the risk of back disorders is not elevated has not been established . Interpretation : Notwithst and ing the bio-psycho-social nature of LBP , and complexities of study ing this area , sufficient evidence exists of a causal relationship between nursing tasks and back disorders to warrant new policies	[ "This study evaluated a two-year multidisciplinary early intervention pilot programme for back-injured nurses employed at a large teaching hospital , using a pre- versus post-programme analysis . The purpose was to ascertain whether this programme could reduce the incidence , morbidity , time lost and cost due to back injuries in the 250 nurses employed on ten targeted high-risk wards . Injuries in the remaining 1395 nurses employed on the other 45 wards were monitored concurrently for comparison . The programme consisted of prompt assessment , treatment and rehabilitation through modified work . Evaluative data were gathered by one research nurse on st and ardized forms at the time of injury , weekly until return to work , and at a six-month follow-up . Time lost and cost data for up to one-year post-injury were derived from workers ' compensation statements . Compared to the two years prior to introduction of the programme , the rates of back injuries and lost-time back injuries decreased by 23 % and 43 % , respectively , on the targeted wards , while these increased on the control wards . Combined expenditure was 32 % lower per injury and 34 % lower per lost-time injury for those in the targeted group who consented to take part in the programme compared to their counterparts on the control wards , as the increased assessment and treatment costs per case attributable to the programme were more than offset by the savings in lower compensation ( wage loss ) costs . This programme thus reduced the incidence and time lost due to back injuries and was cost-beneficial ", "Aims : To identify the work factors that predict intense low back pain ( LBP ) and LBP related sick leaves in nurses ’ aides . Methods : The sample comprised 4266 r and omly selected Norwegian nurses ’ aides , not bothered or only a little bothered by LBP during the previous three months , and not on sick leave when completing a mailed question naire in 1999 . Of these , 3808 ( 89.3 % ) completed a second question naire 3 months later and 3651 ( 85.6 % ) completed a third question naire 15 months later . Intensity of low back symptoms and certified sick leaves attributed to LBP during the observation period were assessed by self reports at the follow ups . Results : After adjustments for LBP during the three months prior to baseline , baseline health complaints , demographic and familial factors , and a series of physical , psychological , and social work factors , logistic regression analyses revealed the following associations : intense low back symptoms were predicted by frequent positioning of patients in bed , perceived lack of support from immediate superior , and perceived lack of pleasant and relaxing culture in the work unit . LBP related sick leaves were predicted by frequent h and ling of heavy objects , medium level of work dem and s , perceived lack of supportive and encouraging culture in the work unit , working night shifts , and working in a nursing home . Long term LBP related sick leaves were associated with changes of work or work tasks during the observation period that result ed in a perceived reduction of support and encouragement at work . Conclusions : Not only frequent mechanical exposures , but also organisational , psychological , and social work factors , such as night shift work , perceived lack of support from superior , and perceived lack of a pleasant and relaxing or supporting and encouraging culture in the work unit , are associated with an increased risk of intense low back symptoms and LBP related sick leaves in nurses ’ aides", "RATIONALE Low back pain ( LBP ) remains a common and costly problem among the nursing profession . Several studies have indicated that LBP is attributed to mentally straining or dem and ing work , fatigue or exhaustion or general work satisfaction . AIMS This study aims to measure the magnitude of LBP among Hong Kong nurses and its association with the work-related psychological strain and patients h and ling activities . RESEARCH METHODS AND MEASURES : A cross-sectional study of Hong Kong hospital nurses was conducted . Three hundred and seventy-seven nurses were recruited from six district hospitals . They were registered nurses or enrolled nurses working full-time for at least 1 month in the current ward . One hundred and seventy-eight ( 47.2 % ) study subjects were r and omly selected from two district hospitals and 199 ( 52.8 % ) study nurses made up the convenience sample . Possible bias from psychological distress , socio-demographics and lifestyle factors was controlled for . Data were collected by face-to-face interviews . The data included work factors ( both psychological stress and patient h and ling activities related to work ) , demographics , psychological distress and lifestyle factors and the occurrence of LBP . RESULTS Of the 377 nurses interviewed , 153 ( 40.6 % ) reported having LBP within the last 12 months . With symptoms of LBP as the outcome , risks were increased where nurses self-reported that they only occasionally or never enjoyed their work [ adjusted odds ratio ( OR ) 2.07 ] , where frequent manual repositioning of patients on the bed was required ( adjusted OR 1.84 ) and where they were required to assist patients while walking ( adjusted OR 2.11 ) after adjustment for other potential confounders . CONCLUSION The results indicate that an association exists between work stress , manual lifting and LBP prevalence . The main route to prevention of LBP among nurses is likely to lie in improved ergonomics and psychological health in their work place . Good posture and correct transferring techniques in ward situations should be reinforced with h and s-on practice performed on nurses ' common types of clients", "The objective of this study was to investigate the low-back loading during common patient-h and ling tasks . Ten female health care workers without formal training in patient h and ling performed nine patient-h and ling tasks including turning , lifting and repositioning a male stroke patient . The low-back loading was quantified by net moment , compression , and shear forces at the L4/L5 joint , measured muscle activity ( EMG ) in erector spinae muscles and rate of perceived exertion ( RPE ; Borg scale ) . The experiments were videotaped with a 50Hz video system using five cameras , and the ground and bedside reaction forces of the health care worker were recorded by means of force platforms and force transducers on the bed . The biomechanical load was calculated using a dynamic 3D seven-segment model of the lower part of the body , and the forces at the L4/L5 joint were estimated by a 14 muscles cross-sectional model of the low back ( optimisation procedure ) . Compression force and torque showed high task dependency whereas the EMG data and the RPE values were more dependent on the subject . The peak compression during two tasks involving lifting the patient ( 4132/4433N ) was significantly higher than all other tasks . Four tasks involving repositioning the patient in the bed ( 3179/3091/2932/3094N ) did not differ , but showed higher peak compression than two tasks turning the patient in the bed ( 1618/2197N ) . Thus , in this study the patient-h and ling tasks could be classified into three groups-characterised by lifting , repositioning or turning-with different levels of peak net torque and compression at the L4/L5 joint", "Back pain disability is a serious and costly problem affecting the nursing profession . The purpose s of this study were to determine risk factors for work-related low back pain ( WRLBP ) in registered nurses and to record the reported use or reasons for nonuse of mechanical lifts . Our hypothesis was that workers who attributed the cause of WRLBP to their own actions would be knowledgeable about back safety , would be more likely to use lifts , and would report less WRLBP . A r and om sample of 270 registered nurses was selected from two acute care hospitals in central Illinois to identify WRLBP risk factors . This cross-sectional study gathered information on individual , physical workload , psychological , and organizational factors that may present a risk for WRLBP . Information was also collected on the use of safety devices and back pain symptoms . The response rate was 50.4 % . Nearly 84 % of respondents had WRLBP in the past , and 36.2 % had WRLBP in the past year that limited movement or interfered with routine activities . Among the risk factors significantly associated with WRLBP were more years worked in nursing , frequent lifting , and low social support . Only 11 % reported that they routinely used mechanical lifting devices , and the primary reason given for failure to use lifting equipment was unavailability of equipment . The reasons for the lack of use of mechanical lifts should be investigated and addressed", "The aim of this Intervention was to evaluate the effect of training on patient-h and ling skills and prospect ively to assess the effect of skill on subsequent back pain and back injuries in nursing . Of a total of 255 nurses , 199 were assessed for their skill in patient-h and ling . One-half ( control group ) received traditional training in patient-h and ling , and the other half ( trained group ) received a curriculum of instruction totaling 40 hours . The skills of both groups were assessed on graduation . The control group was rated as less competent in patient-h and ling . Nurses in both groups were question ed about the prevalence of back pain and incidence of back injuries in the first year after graduation . In multiple regression analysis , the major risk Indicators for back injuries were poor patient-h and ling skill , low numbers of repetitions in the sit-up test , and high work-load scores . High score on the hysteria scale of Middlesex Hospital Question naire was a risk Indicator for all kinds of back pain . Though back pain was Independent of patient-h and ling skill , those rated as “ bad ” or “ poor ” had more back injuries ( 24 % ) than those who had been rated as “ good ” or “ excellent ” ( 2 % ) ( P < 0.001 ) , but the difference between the trained and control groups was not statistically significant . It was concluded that back Injuries may be prevented by the teaching of patient-h and ling skills", "Aims : To assess dose-response relations between occupational exposures to physical and psychosocial factors and the risk of low back pain . Methods : A cohort of 523 subjects , working in nursing homes and homes for the elderly , was followed prospect ively for one year . Physical load for different occupations was assessed by quantitative observations at the workplace . Information on low back pain and other factors was gathered with question naires administered at baseline and at one year . Two outcome measures of low back pain incidence were used : any new episode of pain lasting for at least a few hours during follow up ( LBP ) ; and any new episode of disabling pain that interfered with daily activities during follow up ( LBP/D ) . Hierarchical regression analysis with a spline function was used to estimate dose-response relations . Results : The risk of LBP was not associated with physical factors , controlling for confounders ; but this outcome was inversely associated with age and weakly , though imprecisely , associated with two psychosocial factors — low decision authority and high work dem and s. In contrast , the risk of LBP/D was positively associated with age and not associated with the psychosocial factors . Trunk flexion over 45 degrees was monotonically associated with the risk of LBP/D ; the estimated relative risk was 3.18 ( 95 % CI 1.13 to 9.00 ) for 1 hour and 45 minutes of bending per week ( 90th centile ) , relative to 30 minutes per week . The hierarchical estimates of effect were more stable than were the maximum likelihood estimates . Conclusion : Occupational exposure to trunk flexion over 45 degrees appears to be a risk factor for low back pain with disability among persons employed in nursing homes and homes for the elderly in the Netherl and", "Back injuries are a serious problem for nursing personnel who perform frequent patient-h and ling activities . Common prevention strategies include body mechanics education , technique training , and ergonomic interventions such as the introduction of assistive equipment . This investigation assessed and compared the effectiveness of two patient-h and ling approaches to reducing injury risk . One strategy involved using improved patient-h and ling technique with existing equipment , and the other approach aim ed at eliminating manual patient h and ling through the use of additional mechanical and other assistive equipment . Both intervention arms received training in back care , patient assessment , and use of the equipment available on their particular wards . An analysis of compliance with interventions and the effects of patient-h and ling methods on both peak and cumulative spinal compression and shear during various tasks was conducted . Results showed greater compliance with interventions that incorporated new assistive patient-h and ling equipment , as opposed to those consisting of education and technique training alone . In several tasks , subjects who were untrained or non-compliant with interventions experienced significantly higher peak spinal loading . However , patient-h and ling tasks conducted with the aid of assistive equipment took substantially longer than those performed manually . This , along with variations in techniques , led to increases in cumulative spinal loading with the use of patient-h and ling equipment on some tasks . Thus , the use of mechanical assistive devices may not always be the best approach to reducing back injuries in all situations . No single intervention can be recommended ; instead all patient-h and ling tasks should be examined separately to determine which methods maximize reductions in both peak and cumulative lumbar forces during a manoeuver", "As noted by Wesley Salmon and many others , causal concepts are ubiquitous in every branch of theoretical science , in the practical disciplines and in everyday life . In the theoretical and practical sciences especially , people often base cl aims about causal relations on applications of statistical methods to data . However , the source and type of data place important constraints on the choice of statistical methods as well as on the warrant attributed to the causal cl aims based on the use of such methods . For example , much of the data used by people interested in making causal cl aims come from non-experimental , observational studies in which r and om allocations to treatment and control groups are not present . Thus , one of the most important problems in the social and health sciences concerns making justified causal inferences using non-experimental , observational data . In this paper , I examine one method of justifying such inferences that is especially widespread in epidemiology and the health sciences generally – the use of causal criteria . I argue that while the use of causal criteria is not appropriate for either deductive or inductive inferences , they do have an important role to play in inferences to the best explanation . As such , causal criteria , exemplified by what Bradford Hill referred to as \" aspects of [ statistical ] associations \" , have an indispensible part to play in the goal of making justified causal cl aims", "Injury rates in Intermediate Care ( IC ) facilities are high and the factors related to these injuries are unclear . The objectives of this exploratory sub- study , which is part of a large multi-faceted study in 8 IC facilities are to : ( 1 ) evaluate EMG measured over a full-shift in the back and shoulders of 32 care aides ( CAs ) as an indicator of peak and cumulative workload ( n = 4 x 8 facilities ) ; investigate the relationship between EMG measures and injury indicators ; and explore the relationship between EMG measures and other workload measurements . Lumbar EMG was converted to predicted cumulative spinal compression and ranged in CAs from 11.7 to 22.8 MNs with a mean of 16.4 MNs . Average compression was significantly different during different periods of the day ( p average compression between low and high injury facilities for 3 of 5 periods of the day ( p Peak compressions exceeding 3400 N occurred for very little of the workday ( e.g. 11.25s during the 75 min period pre-breakfast ) . Peak neck/shoulder muscle activity is low ( 99 % APDF ranged from 8.33 % to 28 % MVC ) . Peak and cumulative spinal compression were significantly correlated with lost-time and musculoskeletal injury rates as well as with total tasks observed in the CAs ( p Perceived exertion was only correlated with peak compressions ( p Facilities with low injury rates provided significantly more CAs ( p CAs performed fewer tasks , result ing in less peak and cumulative spinal loading over the day", "OBJECTIVE To evaluate the effectiveness of a program design ed to reduce back pain in nursing aides . METHODS Female nursing aides from a university hospital who had suffered episodes of back pain for at least six months were included in the study . Participants were r and omly divided into a control group and an intervention group . The intervention program involved a set of exercises and an educational component stressing the ergonomic aspect , administered twice a week during working hours for four months . All subjects answered a structured question naire and the intensity of pain was assessed before and after the program using a visual analogue scale ( VAS ) . Student 's t-test or the Wilcoxon Rank Sum Test for independent sample s , and Chi-square test or the Exact Fisher test for categorical analysis , were used . The McNemar test and the Wilcoxon matched pairs test were used to compare the periods before and after the program . RESULTS There was a statistically significant decrease in the frequency of cervical pain in the last two months and in the last seven days in the intervention group . There was also a reduction in cervical pain intensity in the two periods ( 2 months , 7 days ) and lumbar pain intensity in the last 7 days . CONCLUSIONS The results suggest that a program of regular exercise with an emphasis on ergonomics can reduce musculoskeletal symptoms in nursing personnel", "Health professionals h and ling patients are known to be at risk of sustaining work related low back injuries . It is not known whether the use of lifting slings reduces the risk of injury to the lumbar spine for patient h and lers . This study used kinematic variables and subjective ratings of body part stress and lifter preference as measures of relative risk for three two-person techniques for carrying a patient from one chair to another chair . The techniques used no slings , one and two slings respectively . Twenty-two nurses performed five trials each of the three techniques . Kinematic measures of angular displacement , velocity and acceleration were obtained using the lumbar motion monitor and visual analogue scales were used to obtain measures of body part stress for seven body parts . Angular displacement , velocity and acceleration were significantly greater ( p no sling technique compared to techniques using slings . Comparatively small yet significant differences between techniques using slings were recorded for sagittal flexion and rotation . There was no significant difference between one and two sling techniques for other dependent variables . Mean total body stress rating was higher for the no sling technique and all subjects indicated that their first preference was for slings . Although all three measures of risk rated the no sling technique as carrying a higher level of risk than the techniques using slings . No single measure adequately captured all aspects of relative risk . The elimination of manual patient h and ling is thought to be the best option for the reduction of work related back injuries in patient h and lers . Where re sources or technology are not yet adequate to provide practical alternatives and where the use of manual technique for a seat to seat task is unavoidable , the use of patient h and ling slings will reduce the risk", "STUDY DESIGN A prospect i ve study of personal risk factors for first-time low back pain . OBJECTIVES To construct and vali date a multivariate model to predict low back pain . SUMMARY OF BACKGROUND DATA Various physical and psychological factors have been reported to increase the risk of low back pain , but conflicting results may be attributable to inaccurate \" clinical \" measures and to poorly vali date d statistical models . METHODS A total of 403 health care workers aged 18 - 40 years volunteered for the study . None had any history of \" serious \" back pain requiring medical attention or time off work . The volunteers completed the following question naires : the modified somatic perception question naire , the Zung depression scale , and the Health Locus of Control . Anthropometric factors were quantified using st and ard techniques . The 3Space Isotrak device ( Polhemus , VT ) was used to measure lumbar curvature and hip and lumbar spine mobility . Leg and back strength and back muscle fatiguability were measured in functional postures . Postal follow-up question naires , sent after 6 , 12 , 18 , 24 , 30 , and 36 months , inquired about back pain , and multivariate logistic regression was used to identify risk factors at each follow-up . RESULTS The response rate fell from 99 % at 12 months to 90 % at 36 months , at which time 90 volunteers reported \" serious \" back pain and 266 reported \" any \" back pain . The following were consistent predictors of serious back pain : reduced range of lumbar lateral bending , a long back , reduced lumbar lordosis , increased psychological distress , and previous nonserious low back pain . Only the latter three were consistent predictors of \" any \" back pain . Physical factors had the most influence in a sub- population of volunteers who were new to the job . CONCLUSIONS Personal risk factors explained up to 12 % of first-time low back pain", "The aim of this study was to assess , in a prospect i ve cohort of nurses , the risk factors associated with six back pain indicators : back pain ( BP ) , chronic or recurring BP ( occurring often or lasting for more than 3 months ) , cervical ( CP ) , dorsal ( DP ) and lumbar ( LP ) pain and medical treatment for BP . In 1980 , a sample of 469 nurses was r and omly selected from six public sector hospitals . They were followed up and interviewed in 1980 , 1985 and 1990 . BP indicators were assessed on the basis of the nurses ' self-reports during the 12 months before question naire administration in 1990 . The data collected were subjected to cross-sectional analysis in 1990 , to study the associations between the six BP indicators and the risk factors . In a longitudinal analysis , the 1990 BP indicators were analysed in relation to the risk factors present in 1985 among the 210 nurses who were still working in hospitals in 1990 and had not suffered from musculoskeletal disorders ( MSDs ) between 1980 and 1985 . Of the 310 nurses still working in hospitals in 1990 , 57.9 % had suffered from BP within the previous 12 months , 23.6 % of them from CP , 23.0 % from DP and 41.1 % from LP , 40.5 % had suffered from chronic or recurring BP , 31.1 % had undergone treatment and 7.4 % had taken sick leave for BP . In 1990 , BP accounted for 35.8 % of the total number of days of sick leave . The results of the 1990 cross-sectional analysis showed that : ( a ) BP was more frequent among nurses who smoked , experienced symptoms of psychological disorders and had reported stressful factors relating to physical work load ; ( b ) chronic or recurring BP was associated with symptoms of psychological disorders ; ( c ) the frequency of CP increased with age and previous MSDs ; ( d ) DP was more frequent among nurses with children under 3 years and was related to tobacco consumption ; ( e ) LP was associated with symptoms of psychological disorders and physical work load ; and ( f ) treatment for BP was related to symptoms of psychological disorders and fewer of the nurses treated for BP practised a sport . The logistic regressions of the 1985 - 90 longitudinal analysis showed that : ( a ) age was associated with CP ; ( b ) psychosocial factors at work were related to CP ; ( c ) physical work load was associated with chronic or recurring BP ; ( d ) tobacco consumption increased the frequency of BP and DP ; and ( e ) commuting time to work ( ⩾ 1 h/day ) was associated with CP and LP . These results underline the importance of age , tobacco consumption , commuting time to work and work load in the occurrence of BP and also of longitudinal studies in investigating the factors associated with musculoskeletal disorders", "OBJECTIVES This prospect i ve dynamic- population -based study investigated factors involved in the accident process preceding overexertion back injuries among nursing personnel . METHODS The study covered all reported occupational overexertion back injuries due to accidents among of the approximately 24 500 nurses in the Stockholm County hospitals during 1 year . It was assumed that several factors interact in the accident process . Detailed information was obtained for each injury by interviews with the injured nurse and head nurse . Risks in the physical environment were identified using an ergonomic checklist . RESULTS During the study 136 overexertion back injuries were reported . Of the 130 nurses participating in the study , 125 had been injured in connection with patient work . Cluster analysis yielded 6 clusters and their pattern of contributing factors . The most frequent injury occurred during patient transfer in the bed or to or from the bed , without the use of transfer devices , when the patient suddenly lost his or her balance or resisted during the transfer and the nurse had to make a sudden movement . However , there were physical conditions , such as shortcomings in the physical work environment or a lack of a transfer device , that compelled the nurses to perform the tasks under unsafe conditions . CONCLUSIONS The clusters showed a complexity of different kinds of accidents and indicated that the measures for preventing accidents , or for blocking an accident process once started , have to be of different kinds and placed at several different levels in the organization of a workplace", "BACKGROUND Low back pain is common among nurses . Previous studies have shown that the risk of low back pain increases rapidly with greater amounts of physical work and psychological stress , but is inversely related to leisure activities . However , these previous studies were predominantly retrospective in design and not many took account of three factors simultaneously . AIMS This 12-month prospect i ve study examined the relationships between work activities , work stress , sedentary lifestyle and new low back pain . METHODS A total of 144 nurses from six Hong Kong district hospitals completed a face-to-face baseline interview , which was followed-up by a telephone interview . The main study measures were demographic characteristics , work activities , work stress , physical leisure activities and the nature of new low back pain during the 12-month follow-up period . Level of work stress , quality of relationships at work , level of enjoyment experienced at work , and work satisfaction were self-reported . RESULTS Fifty-six ( 38.9 % ) nurses reported experiencing new low back pain . Sedentary leisure time activity was not associated with new low back pain . Being comparatively new on a ward ( adjusted relative risk 2.90 ) , working in bending postures ( adjusted relative risk 2.76 ) and poor work relationships with colleagues ( adjusted relative risk 2.52 ) were independent predictors of new low back pain . CONCLUSION The findings of this study suggest that low back pain is a common problem in the population of nurses in Hong Kong . Being comparatively new on a ward , bending frequently during work and having poor work relationships with colleagues are independent predictors of new low back pain . Training for high-risk work activities and ergonomic assessment of awkward work postures are essential . Moreover , relaxation and team-building workshops for nurses , especially those who are less experienced in the type of work on their current ward , are recommended", "Objective The purpose of this study was to describe the availability of preventive devices and training in relation to neck , shoulder , and back musculoskeletal injuries/disorders ( MSD ) in registered nurses . Summary background data Nurses have one of the highest rates of MSD of any occupation . Studies have shown that mechanical lifting devices and lifting teams can reduce MSD rates and associated costs . Methods Data from 1163 r and omly selected currently working nurses ( 1 + years on the current job ) were collected in anonymous mailed surveys ( 74 % response rate ) . MSD cases had neck , shoulder , and /or back symptoms for at least 1 week , or at least monthly , and moderate or more pain , in the past year . Results Nurses with mechanical lifting devices available were significantly less likely to have neck or back MSDs . Back injury was less likely when lifting teams were available . However , adjustable beds and transfer sheets were associated with greater odds of back MSD . Training in workstation adjustment was associated with significantly lower MSD prevalence , though postural training was not . Conclusions Though use of mechanical devices and lifting teams was limited in nursing workplaces , these prevention strategies were related to reduced odds of MSD . Nursing administrators can use these findings to consider workplace changes", "& NA ; The current investigation studied the effectiveness of a secondary prevention program for nurses with back pain who were deemed at risk for developing a chronic problem . A 2 × 3 repeated measures design was employed with 2 groups and 3 assessment periods . The treatment group received an intervention design ed to reduce current problems , but above all to prevent reinjury and minor pains from becoming chronic medical problems , and it included a physical and behavioral therapy package . The control group was placed on a waiting‐list . Results indicated that the treatment group had significantly greater improvements than the control group for pain intensity , anxiety , sleep quality and fatigue ratings , observed pain behavior , activities , mood , and helplessness . These differences were generally maintained at the 6 month follow‐up . In addition , the treatment group broke a trend for increasing amounts of pain‐related absenteeism , while the control group did not . Taken as a whole , the results suggest that a secondary prevention program aim ed at altering life style factors may represent an effective method for dealing with musculoskeletal pain problems", "OBJECTIVES 1 ) To explore the staff- and work-related risk factors for spinal pain among hospital employees , 2 ) to investigate the effect of staff- and work-related variables on the consequences of spinal pain , such as doctor visits and sick leave . METHODS A mailed survey was carried out in a r and om sample of 2700 employees stratified for occupational categories ( administration staff , nurses , nurse assistants , physicians , support staff and allied health professionals ) . The question naire measured self-reported spinal pain , consequences of pain , and work characteristics . RESULTS The response rate was 48.1 % ( 1298/2700 ) . The one-year prevalence of spinal pain was 67.3 % , highest among nurses ( 75.6 % ) and lowest among support staff ( 54.9 % ) . Reported work characteristics associated with spinal pain included frequent work at a poorly adapted work station ( odds ratio ( OR ) 1.90 [ 1.24 - 2.93 ] ) and having to maintain a position for a long time ( OR 1.71 [ 1.25 - 2.34 ] ) . No significant correlations were observed with lifting , patient h and ling , material h and ling , or working on nightshift . Sickness leave due to spinal pain was significantly associated with duration of pain episode ( OR 4.08 for>3 months compared to less than 10 days ) , and with work categories ( OR 2.58 for nurse assistants compared to nurses ) . CONCLUSION In this population of hospital employees , being a nurse , working at a poorly adapted work place , and having to maintain positions for a long time were related independently to spinal pain . Nurse assistants had a higher risk of work absenteeism", "The purpose of this multicenter prospect i ve cohort study was to assess personal and job-related factors as determinants of incidence of reported back injuries among nurses . The study population included 5,649 nurses who were surveyed by question naire and then observed for a 12-month study period . An annual injury rate of 4.9 % was observed . Four factors were found to be significant ( P less than .01 ) predictors of back injury . All four factors -- service area , lifting , job category , and previously reported back injury -- maintain significance when a forward stepping model of logistic regression is applied . The adjusted odds ratios observed are 4.26 for service areas where lifting occurs most as compared with areas where lifting occurs least ; 2.19 for daily lifters v light , occasional , and nonlifters ; 1.77 for nursing aides v registered nurses and supervisory personnel ; and 1.73 for individuals who have previously reported back injury v those who have not reported previous injury . These findings strongly suggest that job-related rather than personal characteristics are the major predictors of back injury in nurses", "Aims : To study the influence of work related physical and psychosocial factors and individual characteristics on the occurrence of low back pain among young and pain free workers . Methods : The Belgian Cohort Back Study was design ed as a prospect i ve cohort study . The study population of this paper consisted of 716 young healthcare or distribution workers without low back pain lasting seven or more consecutive days during the year before inclusion . The median age was 26 years with an interquartile range between 24 and 29 years . At baseline , these workers filled in a question naire with physical exposures , work related psychosocial factors and individual characteristics . One year later , the occurrence of low back pain lasting seven or more consecutive days and some of its characteristics were registered by means of a question naire . To assess the respective role of predictors at baseline on the occurrence of low back pain in the following year , Cox regression with a constant risk period for all subjects was applied . Results : After one year of follow up , 12.6 % ( 95 % CI 10.1 to 15.0 ) of the 716 workers had developed low back pain lasting seven or more consecutive days . An increased risk was observed for working with the trunk in a bent and twisted position for more than two hours a day ( RR 2.2 , 95 % CI 1.2 to 4.1 ) , inability to change posture regularly ( RR 2.1 , 95 % CI 1.3 to 3.5 ) , back complaints in the year before inclusion ( RR 1.7 , 95 % CI 1.1 to 2.8 ) , and high scores of pain related fear ( RR 1.8 , 95 % CI 1.0 to 3.1 ) . Work related psychosocial factors and physical factors during leisure time were not predictive . Conclusion : This study highlighted the importance of physical work factors and revealed the importance of high scores of pain related fear in the development of low back pain among young workers", "The personnel at a geriatric hospital were r and omized into two groups . One group was allowed to exercise during working hours to improve back muscle strength , endurance , and coordination . The other group did not participate in the exercise program and received no further advice or information . After 13 months , the training group had increased back muscle strength . One subject had been absent from work 28 days in the training group whereas 12 subjects had been absent 155 days from work because of low back pain in the control group ( P back pain complaints and intensity of back pain in the training group also decreased in a statistically significant way . Every hour spent by the physiotherapist on the training group reduced the work absence among the participants by 1.3 days , result ing in a cost/benefit ratio greater than 10", "This is the first of two articles to report a biomechanical evaluation and psychophysical assessment of nine battery-powered lifts , a sliding board , a walking belt , and a baseline manual method for transferring nursing home residents from a bed to a chair . The objectives of the biomechanical evaluation were : ( 1 ) to investigate the effects of transfer method and resident weight on the biomechanical stress to nursing assistants performing the transferring task , and ( 2 ) to identify resident-transferring methods that could reduce the biomechanical stress to the nursing assistants . Nine nursing assistants served as test subjects ; two elderly persons participated as residents . A four-camera motion analysis system , two force platforms , and a three-dimensional biomechanical model were used to measure biomechanical load . The results indicate that transfer method and resident weight affect a nursing assistant 's low-back loading . The basket-sling and overhead lift devices significantly reduced the nursing assistants ' back-compressive forces during the preparation phase of a resident transfer . In addition , the use of basket-sling , overhead , and st and -up lifts removed about two-thirds of the exposure to low-back stress ( lifting activities per transfer ) as compared to the baseline manual method . Thus , the use of these devices reduces biomechanical stress , and thereby will decrease the occurrence of resident-h and ling-related low-back injuries . Furthermore , lifting device maneuvering forces were found to be significantly different and a number of design /use problems were identified with various assistive devices . The second article will detail the psychophysical assessment of the same resident-transferring methods", "Objectives Prevention of occupational low back pain ( LBP ) in nurses is a research priority . Recent research suggests intervening before commencing nursing employment is ideal ; however , identification of modifiable risk factors is required . The objective of this study was to investigate modifiable personal characteristics that predicted new-onset LBP in nursing students . Methods This prospect i ve study was conducted on female nursing students ( n=117 ) without LBP at baseline to predict new-onset LBP ( an episode of significant LBP during the follow-up period ) . At the 12-month follow-up , participants with ( n=31 ) and without new-onset LBP ( n=76 ) were compared across baseline social or lifestyle , psychologic ( distress , back pain beliefs , coping strategies , and catastrophising ) , and physical ( spinal postures and spinal kinematics in functional tasks , leg and back muscle endurance , spinal repositioning error , and cardiovascular fitness ) characteristics . Results Participants response rate at follow-up was excellent ( 91 % ) . After controlling for earlier LBP , age , and BMI , regression analysis showed that modifiable social or lifestyle , psychologic and physical characteristics ( namely , smoking , increased physical activity , higher stress , reduced back muscle endurance , greater posterior pelvic rotation in slump sitting , and more accurate spinal repositioning in sitting ) were significant and independent predictors of new-onset LBP at follow-up . Inclusion of these factors in multivariate logistic regression analysis , with significant new-onset LBP as the outcome , result ed in a substantial model R2 of 0.45 . Discussion Modifiable personal characteristics across multiple domains are associated with new-onset LBP in female nursing students . These findings may have implication s for the development of prevention and management interventions for LBP in nurses", "Study Design . R and omized controlled trial ( RCT ) . Objectives . To compare the effectiveness of training and equipment to reduce musculoskeletal injuries , increase comfort , and reduce physical dem and s on staff performing patient lifts and transfers at a large acute care hospital . Summary of Background Data . Back injury to nursing staff during patient h and ling tasks is a major issue in health care . The value of mechanical assistive devices in reducing injuries to these workers is unclear . Methods . This three-armed RCT consisted of a “ control arm , ” a “ safe lifting ” arm , and a “ no strenuous lifting ” arm . A medical , surgical , and rehabilitation ward were each r and omly assigned to each arm . Both intervention arms received intensive training in back care , patient assessment , and h and ling techniques . Hence , the “ safe lifting ” arm used improved patient h and ling techniques using manual equipment , whereas the “ no strenuous lifting ” arm aim ed to eliminate manual patient h and ling through use of additional mechanical and other assistive equipment . Results . Frequency of manual patient h and ling tasks was significantly decreased on the “ no strenuous lifting ” arm . Self-perceived work fatigue , back and shoulder pain , safety , and frequency and intensity of physical discomfort associated with patient h and ling tasks were improved on both intervention arms , but staff on the mechanical equipment arm showed greater improvements . Musculoskeletal injury rates were not significantly altered . Conclusions . The “ no strenuous lifting ” program , which combined training with assured availability of mechanical and other assistive patient h and ling equipment , most effectively improved comfort with patient h and ling , decreased staff fatigue , and decreased physical dem and s. The fact that injury rates were not statistically significantly reduced may reflect the less sensitive nature of this indicator compared with the subjective indicators", "Study Design . A 3-year prospect i ve cohort study among workers of 34 companies in the Netherl and s. Objectives . To investigate the relation between flexion and rotation of the trunk and lifting at work and the occurrence of low back pain . Summary of Background Data . Previous studies on work-related physical risk factors for low back pain either lacked quantification of the physical load or did not take confounding by individual and psychosocial factors into account . Methods . The study population consisted of 861 workers with no low back pain at baseline and complete data on the occurrence of low back pain during the 3-year follow-up period . Physical load at work was assessed by means of analyses of video-recordings . Information on other risk factors and the occurrence of low back pain was obtained by means of self-administered question naires . Results . An increased risk of low back pain was observed for workers who worked with the trunk in a minimum of 60 ° of flexion for more than 5 % of the working time ( RR 1.5 , 95 % CI 1.0–2.1 ) , for workers who worked with the trunk in a minimum of 30 ° of rotation for more than 10 % of the working time ( RR 1.3 , 95 % CI 0.9–1.9 ) , and for workers who lifted a load of at least 25 kg more than 15 times per working day ( RR 1.6 , 95 % CI 1.1–2.3 ) . Conclusions . Flexion and rotation of the trunk and lifting at work are moderate risk factors for low back pain , especially at greater levels of exposure", "Objective To investigate the association of physical and psychosocial risk factors with musculoskeletal disorders ( MSDs ) in New Zeal and nurses , postal workers and office workers . Design A cross-sectional postal survey asking about demographic , physical and psychosocial factors and MSDs . Participants A total of 911 participants was r and omly selected ; nurses from the Nursing Council of New Zeal and data base ( n=280 ) , postal workers from their employer 's data base ( n=280 ) and office workers from the 2005 electoral roll ( n=351 ) . Outcome Measures Self-reported pain in the low back , neck , shoulder , elbow , wrist/h and or knee lasting more than 1 day in the month before the survey . Results The response rate was 58 % , 443 from 770 potential participants . 70 % ( n=310 ) reported at least one MSDs . Physical work tasks were associated with low back ( odds ratio ( OR ) 1.35 , 95 % CI 1.14 to 1.6 ) , shoulder ( OR 1.41 , 95 % CI 1.17 to 1.69 ) , elbow ( OR 1.14 , 95 % CI 1.13 to 1.83 ) and wrist/h and pain ( OR 1.39 , 95 % CI 1.15 to 1.69 ) . Job strain had the strongest association with neck pain ( OR 3.46 , 95 % CI 1.30 to 9.21 ) and wrist/h and pain . Somatisation was weakly associated with MSDs at most sites . Better general and mental health status were weakly associated with lower odds of MSDs . Conclusions In injury prevention and rehabilitation the physical nature of the work needs to be addressed for most MSDs , with modest decreases in risk seemingly possible . Addressing job strain could provide significant benefit for those with neck and wrist/h and pain , while the effects of somatisation and the promotion of good mental health may provide smaller but global benefits", "A prospect i ve epidemiologic study was conducted in two units ( 140 beds and 57 nursing assistants ) of a nursing home to demonstrate the efficacy of an ergonomic intervention strategy to reduce back stress to nursing personnel . The total programme involved the following : determining patient h and ling tasks perceived to be most stressful by the nursing assistants ( NAs ) ; performing an ergonomic evaluation of these tasks ; and conducting a laboratory study to select patient transferring devices perceived to produce less physical stress than existing manual patient-h and ling methods . The intervention phase included training NAs in the use of these devices , modifying toilets and shower rooms , and applying techniques to patient care . Immediately after completing the intervention programme , a post-intervention analysis ( which lasted eight months in unit 1 and four months in unit 2 ) was performed . A biomechanical evaluation of the physical dem and s required to perform stressful patient-h and ling tasks showed that the mean compressive force on the L5/S1 disc , the mean h and force required to make a transfer , and the strength requirements ( expressed as percentage female population capable ) were 1964 N , 122 N , and 83 % after intervention as compared to 4751 N , 312 N , and 41 % before intervention . Subjectively , the mean rating of perceived exertion was less than ' very light ' after intervention as compared to between ' somewhat hard ' and ' hard ' before intervention . Overall , the mean acceptability rates for the walking belt and the mechanical hoist were 81 % and 87 % for patient transfers . The incidence rate for back injuries prior to the intervention , 83 per 200,000 work-hours , decreased to 47 per 200,000 work-hours after the intervention . There were no injuries result ing in lost or restricted work days during the last four months of the post-intervention . It is concluded that an appropriate ergonomic intervention programme offers great promise in reducing physical stress and risk of low-back pain to nursing personnel . However , large-scale studies in different nursing homes are needed to confirm the above findings", "Although patient h and lers suffer from low-back injuries at an alarming rate worldwide , there has been limited research quantifying the risk for the specific tasks performed by the patient h and lers . The current study used both a comprehensive evaluation system ( low-back disorder risk model ) and theoretical model ( biomechanical spinal loading model ) to evaluate risk of LBD of 17 participants ( 12 experienced and five inexperienced ) performing several patient h and ling tasks . Eight of the participants were female and nine were male . Several patient transfers were evaluated as well as repositioning of the patient in bed ; these were performed with one and two people . The patient transfers were between bed and wheelchair ( fixed and removable arms ) and between commode chair and hospital chair . A ' st and ard ' patient ( a 50 kg co-operative female ; non-weight bearing but had use of upper body ) was used in all patient h and ling tasks . Overall , patient h and ling was found to be an extremely hazardous job that had substantial risk of causing a low-back injury whether with one or two patient h and lers . The greatest risk was associated with the one-person transferring techniques with the actual task being performed having a limited effect . The repositioning techniques were found to have significant risk of LBD associated with them with the single hook method having the highest LBD risk and spinal loads that exceeded the tolerance limits ( worst patient h and ling job ) . The two-person draw sheet repositioning technique had the lowest LBD risk and spinal loads but still had relatively high spinal loads and LBD risk . Thus , even the safest of tasks ( of the tasks evaluated in this study ) had significant risk . Additionally , the current study represented a ' best ' case scenario since the patient was relatively light and co-operative . Thus , patient h and ling in real situations such as in a nursing home , would be expected to be worse . Therefore , to have an impact on LBD , it is necessary to provide mechanical lift assist devices", "Abstract Objective : To assess the impact of h and ling patients and indicators of individual susceptibility on risk of low back pain in nurses . Design : Prospect i ve cohort study with follow up by repeated self administered question naires every three months over two years . Setting : NHS university hospitals trust . Subjects : 961 female nurses who had been free from low back pain for at least one month at the time of completing a baseline question naire . Main outcome measures : Incidence of new low back pain during follow up and of pain leading to absence from work . Results : Of 838 women who provided data suitable for analysis , 322 ( 38 % ) developed low back pain during follow up ( mean 18.6 months ) , including 93 ( 11 % ) whose pain led to absence from work . The strongest predictor of new low back pain was earlier history of the symptom , and risk was particularly high if previous pain had lasted for over a month in total and had occurred within the 12 months before entry to the study ( incidence during follow up 66 % ) . Frequent low mood at baseline was strongly associated with subsequent absence from work for back pain ( odds ratio 3.4 ; 95 % confidence interval 1.4 to 8.2 ) . After adjustment for earlier history of back pain and other potential confounders , risk was higher in nurses who reported frequent manual transfer of patients between bed and chair , manual repositioning of patients on the bed , and lifting patients in or out of the bath with a hoist . Conclusions : Of the indicators of individual susceptibility that were examined , only history of back trouble was sufficiently predictive to justify selective exclusion of some applicants for nursing posts . The main route to prevention of back disorders among nurses is likely to lie in improved ergonomics . Key messages A history of back trouble , particularly if recent and prolonged , is highly predictive of new episodes of back pain There are grounds for excluding nurses with recent and prolonged back pain from the most physically dem and ing jobs Age , height , and weight are not sufficiently discriminatory for risk of back pain to influence selection and appointment of nurses Back pain is more common in nurses who lift and move patients frequently without the use of mechanical aids Controlled trials are needed to assess the benefits of ergonomic intervention aim ed at prevention of back pain in", " One hundred seventy – one nurses had their back strength evaluated on an isokinetic lifting device and filled out an epidemiologic question naire . They were then followed prospect ively for 2 years to determine the incidence of job – related low – back injuries . The data were analyzed to determine if the injury incidence correlated with any of the strength or epidemiologic variables collected during the original evaluation . Average peak force measured during the isokinetic lift was 63.8 kg + 13.6 kg at a lift speed of 30.5 cm/sec and 59.1 kg + 14.9 kg at a lift speed of 45.7 cm/sec . Sixteen nurses reported an occurrence of job – related low – back pain or injury during the 2–year prospect i ve period . Discriminate statistical techniques showed that none of the strength or epidemiologic variables correlated with the incidence of pain or injury or explained significant amounts of variance when the variables were regressed on strength or work calculated from the lift force/lift height data . It was concluded that in this high risk population , in which loads are heavy and lifting postures are variable , the use of low – back strength or prior history of pain or injury are poor predictors as to subsequent low – back pain or injury", "OBJECTIVE --To investigate the risk factors for low back pain in hospital nurses , with particular emphasis on the role of specific nursing activities . METHODS --A cross sectional survey of 2405 nurses employed by a group of teaching hospitals was carried out . Self administered question naires were used to collect information about occupational activities , non-occupational risk factors for back symptoms , and history of low back pain . RESULTS --The overall response rate was 69 % . Among 1616 women , the lifetime prevalence of back pain was 60 % and the one year period prevalence 45 % . 10 % had been absent from work because of back pain for a cumulative period exceeding four weeks . Rates in men were generally similar to those in women . In women back pain during the previous 12 months was weakly associated with height , and was significantly more common in those who reported frequent non-musculoskeletal symptoms such as headache and low mood . After adjustment for height and non-musculoskeletal symptoms , significant associations were found with frequency of manually moving patients around on the bed , manually transferring patients between bed and chair , and manually lifting patients from the floor . In contrast , no clear increase in risk was found in relation to transfer of patients with canvas and poles , manually lifting patients in and out of the bath , or lifting patients with mechanical aids . Confirmation of these findings is now being sought in a prospect i ve study of the same population . CONCLUSIONS --This study confirms that low back pain is highly prevalent among nurses and is associated with a high level of sickness absence . People who often report non-musculoskeletal symptoms were significantly more likely to report low back pain . Specific manual h and ling tasks were associated with an increased risk of back pain ; however , no such association was found with mechanised patient transfers", "This article describes how the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) approach to grading the quality of evidence and strength of recommendations considers the Bradford Hill criteria for causation and how GRADE may relate to questions in public health . A primary concern in public health is that evidence from non-r and omised studies may provide a more adequate or best available measure of a public health strategy 's impact , but that such evidence might be grade d as lower quality in the GRADE framework . GRADE , however , presents a framework that describes both criteria for assessing the quality of research evidence and the strength of recommendations that includes considerations arising from the Bradford Hill criteria . GRADE places emphasis on recommendations and in assessing quality of evidence ; GRADE notes that r and omisation is only one of many relevant factors . This article describes how causation may relate to developing recommendations and how the Bradford Hill criteria are considered in GRADE , using examples from the public health literature with a focus on immunisation" ]	411895fa-06ff-11f0-808a-c43d1ab1c353
Importance Cannabinoid drugs are widely used as analgesics , but experimental pain studies have produced mixed findings . The analgesic properties of cannabinoids remain unclear . Objective To conduct a systematic review and meta- analysis of the association between cannabinoid drug administration and experimental pain outcomes in studies of healthy adults . Design , Setting , and Participants A systematic search of PubMed , EMBASE , MEDLINE , PsycINFO , and CINAHL was conducted from the inception of each data base to September 30 , 2017 . Studies were eligible for inclusion if they met criteria , including healthy participants and an experimentally controlled administration of any cannabinoid preparation in a quantified dose . Studies that used participants with chronic pain were excluded . Data extracted included study characteristics , cannabinoid types and doses , sex composition , and outcomes . Study quality was assessed using a validity measure previously established in published review s. R and om-effects meta-analyses were used to pool data and generate summary estimates . Main Outcomes and Measures Experimental pain threshold , pain tolerance , pain intensity , pain unpleasantness , and mechanical hyperalgesia . Results Eighteen placebo-controlled studies ( with 442 participants ) were identified . Of the 442 participants , 233 ( 52.7 % ) were male and 209 ( 47.3 % ) were female . For sample ages , 13 ( 72 % ) of the 18 studies reported a mean sample age ( 26.65 years ) , 4 ( 22 % ) reported a range , and 1 ( 6 % ) reported a median value . The search yielded sufficient data to analyze 18 pain threshold comparisons , 22 pain intensity comparisons , 9 pain unpleasantness comparisons , 13 pain tolerance comparisons , and 9 mechanical hyperalgesia comparisons . Cannabinoid administration was associated with small increases in pain threshold ( Hedges g = 0.186 ; 95 % CI , 0.054 - 0.318 ; P = .006 ) , small to medium increases in pain tolerance ( Hedges g = 0.225 ; 95 % CI , 0.015 - 0.436 ; P = .04 ) , and a small to medium reduction in the unpleasantness of ongoing experimental pain ( Hedges g = 0.288 ; 95 % CI , 0.104 - 0.472 ; P = .002 ) . Cannabinoid administration was not reliably associated with a decrease in experimental pain intensity ( Hedges g = 0.017 ; 95 % CI , −0.120 to 0.154 ; P = .81 ) or mechanical hyperalgesia ( Hedges g = 0.093 ; 95 % CI , −0.059 to 0.244 ; P = .23 ) . The mean quality rating across studies was good . Conclusions and Relevance Cannabinoid drugs may prevent the onset of pain by producing small increases in pain thresholds but may not reduce the intensity of experimental pain already being experienced ; instead , cannabinoids may make experimental pain feel less unpleasant and more tolerable , suggesting an influence on affective processes . Cannabis-induced improvements in pain-related negative affect may underlie the widely held belief that cannabis relieves pain	[ "The aim of the present study was to investigate the effects of nabilone on capsaicin‐induced pain and hyperalgesia , as well as on biomarkers of cannabinoid central nervous system ( CNS ) effects . A r and omized , double‐blind , placebo‐controlled , crossover study was conducted in 30 healthy male volunteers receiving single doses of nabilone ( 1 , 2 or 3 mg ) . Pain intensity after intradermal capsaicin injections in the forearm was assessed by continuous visual analogue scale ( 0–100 mm ) . Capsaicin cream was applied to the calf to induce hyperalgesia . Primary hyperalgesia was assessed by measuring heat pain thresholds , whereas secondary hyperalgesia was assessed by measuring the area where light tactile stimulation was felt to be painful . Pain and hyperalgesia were measured at baseline and 2–3.5 h after dosing . The CNS effects were assessed at baseline and up to 24 h after dosing using visual analogue mood scales for feeling ‘ stimulated ’ , ‘ anxious ’ , ‘ se date d ’ and ‘ down ’ . Plasma sample s for pharmacokinetic analysis were obtained up to 24 h after drug administration . Nabilone did not significantly attenuate either ongoing pain or primary or secondary hyperalgesia , whereas dose‐dependent CNS effects were observed from 1.5 to 6 h after dosing , being maximal at 4–6 h. Plasma concentrations of nabilone and its metabolite carbinol were maximal 1–2 h after dosing . Adverse events ( AE ) were common on nabilone treatment . Four subjects withdrew due to pronounced CNS AE ( anxiety , agitation , altered perception , impaired consciousness ) . Although nabilone had marked CNS effects , no analgesic or antihyperalgesic effects were observed", "Medicinal cannabis has already entered mainstream medicine in some countries . This systematic review ( SR ) aim ed at evaluating the efficacy , acceptability and safety of cannabis-based medicines for chronic pain management . Qualitative systematic review of SRs of r and omized controlled trials with cannabis-based medicines for chronic pain management . The Cochrane data bases of SRs , Data base of Abstract s of Review s of Effects and PubMed were search ed for SR published in the period January 2009 to January 2017 . Assessment of the method ological quality of SR was performed by the AMSTAR checklist . Out of 748 papers identified , 10 SRs met the inclusion criteria . The method ological quality was high in four and moderate in six SRs . There were inconsistent findings of four SRs on the efficacy of cannabis-based medicines in neuropathic pain and of one SR for painful spasms in multiple sclerosis . There were consistent results that there was insufficient evidence of any cannabis-based medicine for pain management in patients with rheumatic diseases ( three SRs ) and in cancer pain ( two SRs ) . Cannabis-based medicines undoubtedly enrich the possibilities of drug treatment of chronic pain conditions . It remains the responsibility of the health care community to continue to pursue rigorous study of cannabis-based medicines to provide evidence that meets the st and ard of 21st century clinical care . SIGNIFICANCE We provide an overview of systematic review s on the efficacy , tolerability and safety of cannabis-based medicines for chronic pain management . There are inconsistent findings of the efficacy of cannabinoids in neuropathic pain and painful spasms in multiple sclerosis . There are inconsistent results on tolerability and safety of cannabis-based medicines for any chronic pain", "The effect of marijuana and placebo on pain tolerance was compared in cannabis-experienced and naive subjects . A statistically significant increase in tolerance was observed after smoking marijuana . Although there was no statistically significant interaction between the drug effect and having had previous cannabis experience , there was a definite trend towards a greater increase for the experienced ( 16 % ) compared to the naive group(8 % )", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "Evidence for an analgesic interaction between delta-9-tetrahydrocannabinol ( Delta(9)-THC ) and morphine was sought using an experimental pain model applied to normal volunteers . The study incorporated a double blinded , four treatment , four period , four sequence , crossover design . Subjects received Delta(9)-THC 5 mg orally or placebo and 90 min later morphine 0.02 mg/kg intravenously or placebo . Fifteen minutes later subjects rated the pain associated with the application of thermal stimuli to skin using two visual analog scales , one for the sensory and one for the affective aspects of pain . Among sensory responses , neither morphine nor Delta(9)-THC had a significant effect at the doses used , and there was no significant interaction between the two . Among affective responses , although neither morphine nor Delta(9)-THC had a significant effect , there was a positive analgesic interaction between the two ( p = 0.012 ) , indicating that the combination had a synergistic affective analgesic effect . The surprisingly limited reported experimental experience in humans does not support a role for Delta(9)-THC as an analgesic or as an adjunct to cannabinoid analgesia , except for our finding of synergy limited to the affective component of pain . Comparison of our results with those of others suggests that extrapolation from experimental pain models to the clinic is not likely to be a straight-forward process . Future studies of Delta(9)-THC or other cannabinoids in combination with opiates should focus upon clinical rather than experimental pain", "The aim of the present study was to develop a physiologically compatible inhalation solution of delta-9-tetrahydrocannabinol ( THC ) , and to compare the pharmacokinetic and analgesic properties of pulmonal THC versus pulmonal placebo and intravenous ( iv ) THC , respectively . Eight healthy volunteers were included in this r and omized , double-blind , crossover study . The aqueous THC formulations were prepared by using a solubilization technique . iv THC ( 0.053 mg/kg body weight ) , pulmonal THC ( 0.053 mg/kg ) , or a placebo inhalation solution was administered as single dose . At defined time points , blood sample s were collected , and somatic and psychotropic side effects as well as vital functions monitored . An ice water immersion test was performed to measure analgesia . Using a pressure-driven nebulizer , the pulmonal administration of the THC liquid aerosol result ed in high THC peak plasma levels within minutes . The bioavailability of the pulmonal THC was 28.7 + /- 8.2 % ( mean + /- SEM ) . The side effects observed after pulmonal THC were coughing and slight irritation of the upper respiratory tract , very mild psychotropic symptoms , and headache . The side effects after iv THC were much more prominent . Neither pulmonal nor iv THC significantly reduced experimentally induced pain", "Recent studies have demonstrated the therapeutic potential of cannabinoids to treat pain , yet none have compared the analgesic effectiveness of smoked marijuana to orally administered Δ9-tetrahydrocannabinol ( THC ; dronabinol ) . This r and omized , placebo-controlled , double-dummy , double-blind study compared the magnitude and duration of analgesic effects of smoked marijuana and dronabinol under well-controlled conditions using a vali date d experimental model of pain . Healthy male ( N=15 ) and female ( N=15 ) daily marijuana smokers participated in this outpatient study comparing the analgesic , subjective , and physiological effects of marijuana ( 0.00 , 1.98 , or 3.56 % THC ) to dronabinol ( 0 , 10 , or 20 mg ) . Pain response was assessed using the cold-pressor test ( CPT ) : participants immersed their left h and in cold water ( 4 ° C ) , and the time to report pain ( pain sensitivity ) and withdraw the h and from the water ( pain tolerance ) were recorded . Subjective pain and drug effect ratings were also measured as well as cardiovascular effects . Compared with placebo , marijuana and dronabinol decreased pain sensitivity ( 3.56 % ; 20 mg ) , increased pain tolerance ( 1.98 % ; 20 mg ) , and decreased subjective ratings of pain intensity ( 1.98 , 3.56 % ; 20 mg ) . The magnitude of peak change in pain sensitivity and tolerance did not differ between marijuana and dronabinol , although dronabinol produced analgesia that was of a longer duration . Marijuana ( 1.98 , 3.56 % ) and dronabinol ( 20 mg ) also increased abuse-related subjective ratings relative to placebo ; these ratings were greater with marijuana . These data indicate that under controlled conditions , marijuana and dronabinol decreased pain , with dronabinol producing longer-lasting decreases in pain sensitivity and lower ratings of abuse-related subjective effects than marijuana", "Background : Although the pre clinical literature suggests that cannabinoids produce antinociception and antihyperalgesic effects , efficacy in the human pain state remains unclear . Using a human experimental pain model , the authors hypothesized that inhaled cannabis would reduce the pain and hyperalgesia induced by intradermal capsaicin . Methods : In a r and omized , double-blinded , placebo-controlled , crossover trial in 15 healthy volunteers , the authors evaluated concentration – response effects of low- , medium- , and high-dose smoked cannabis ( respectively 2 % , 4 % , and 8 % 9-&dgr;-tetrahydrocannabinol by weight ) on pain and cutaneous hyperalgesia induced by intradermal capsaicin . Capsaicin was injected into opposite forearms 5 and 45 min after drug exposure , and pain , hyperalgesia , tetrahydrocannabinol plasma levels , and side effects were assessed . Results : Five minutes after cannabis exposure , there was no effect on capsaicin-induced pain at any dose . By 45 min after cannabis exposure , however , there was a significant decrease in capsaicin-induced pain with the medium dose and a significant increase in capsaicin-induced pain with the high dose . There was no effect seen with the low dose , nor was there an effect on the area of hyperalgesia at any dose . Significant negative correlations between pain perception and plasma & dgr;-9-tetrahydrocannabinol levels were found after adjusting for the overall dose effects . There was no significant difference in performance on the neuropsychological tests . Conclusions : This study suggests that there is a window of modest analgesia for smoked cannabis , with lower doses decreasing pain and higher doses increasing pain", "This article review s recent research on cannabinoid analgesia via the endocannabinoid system and non-receptor mechanisms , as well as r and omized clinical trials employing cannabinoids in pain treatment . Tetrahydrocannabinol ( THC , Marinol ® ) and nabilone ( Cesamet ® ) are currently approved in the United States and other countries , but not for pain indications . Other synthetic cannabinoids , such as ajulemic acid , are in development . Crude herbal cannabis remains illegal in most jurisdictions but is also under investigation . Sativex ® , a cannabis derived oromucosal spray containing equal proportions of THC ( partial CB1 receptor agonist ) and cannabidiol ( CBD , a non-euphoriant , anti-inflammatory analgesic with CB1 receptor antagonist and endocannabinoid modulating effects ) was approved in Canada in 2005 for treatment of central neuropathic pain in multiple sclerosis , and in 2007 for intractable cancer pain . Numerous r and omized clinical trials have demonstrated safety and efficacy for Sativex in central and peripheral neuropathic pain , rheumatoid arthritis and cancer pain . An Investigational New Drug application to conduct advanced clinical trials for cancer pain was approved by the US FDA in January 2006 . Cannabinoid analgesics have generally been well tolerated in clinical trials with acceptable adverse event profiles . Their adjunctive addition to the pharmacological armamentarium for treatment of pain shows great promise", "Background The grading of recommendation , assessment , development and evaluation ( GRADE ) approach is widely implemented in health technology assessment and guideline development organisations throughout the world . GRADE provides a transparent approach to reaching judgements about the quality of evidence on the effects of a health care intervention , but is complex and therefore challenging to apply in a consistent manner . Methods We developed a checklist to guide the research er to extract the data required to make a GRADE assessment . We applied the checklist to 29 meta-analyses of r and omised controlled trials on the effectiveness of health care interventions . Two review ers used the checklist for each paper and used these data to rate the quality of evidence for a particular outcome . Results For most ( 70 % ) checklist items , there was good agreement between review ers . The main problems were for items relating to indirectness where considerable judgement is required . Conclusions There was consistent agreement between review ers on most items in the checklist . The use of this checklist may be an aid to improving the consistency and reproducibility of GRADE assessment s , particularly for inexperienced users or in rapid review s without the re sources to conduct assessment s by two research ers independently", "The purpose of this study was to determine whether marijuana produced dose-dependent antinociception in humans and , if so , whether endogenous opiates modulate this effect . A total of five male regular marijuana users participated in three test sessions during which they smoked cigarettes containing 0 % ( placebo ) and 3 . 55 % Delta(9)-tetrahydrocannabinol ( Delta(9)-THC ) ( active ) . Each of four controlled smoking bouts per session , spaced at 40-min intervals , consisted of nine puffs from active and placebo cigarettes ( three cigarettes , three puffs per cigarette , one puff per min ) . During successive bouts , participants smoked 0 , 3 , 6 and 9 ( 0 , 3 , 9 and 18 cumulative ) puffs from active marijuana cigarettes , with the remainder of puffs from placebo cigarettes . Test sessions were identical , except for naltrexone 0 , 50 or 200 mg p.o . ( r and omized , double-blind ) administration 1 h before the first smoking bout on the different days . Before smoking , between smoking bouts and postsmoking , participants completed an assessment battery that included antinociceptive ( finger withdrawal from radiant heat stimulation ) , biological , subjective , observer-rated signs and performance measures . Marijuana produced significant dose-dependent antinociception ( increased finger withdrawal latency ) and biobehavioral effects . Naltrexone did not significantly influence marijuana dose-effect curves , suggesting no role of endogenous opiates in marijuana-induced antinociception under these conditions", "From folk medicine and anecdotal reports it is known that Cannabis may reduce pain . In animal studies it has been shown that delta‐9‐tetrahydrocannabinol ( THC ) has antinociceptive effects or potentiates the antinociceptive effect of morphine . The aim of this study was to measure the analgesic effect of THC , morphine , and a THC‐morphine combination ( THC‐morphine ) in humans using experimental pain models . THC ( 20 mg ) , morphine ( 30 mg ) , THC‐morphine ( 20 mg THC+30 mg morphine ) , or placebo were given orally and as single doses . Twelve healthy volunteers were included in the r and omized , placebo‐controlled , double‐blinded , crossover study . The experimental pain tests ( order r and omized ) were heat , cold , pressure , single and repeated transcutaneous electrical stimulation . Additionally , reaction time , side‐effects ( visual analog scales ) , and vital functions were monitored . For the pharmacokinetic profiling , blood sample s were collected . THC did not significantly reduce pain . In the cold and heat tests it even produced hyperalgesia , which was completely neutralized by THC‐morphine . A slight additive analgesic effect could be observed for THC‐morphine in the electrical stimulation test . No analgesic effect result ed in the pressure and heat test , neither with THC nor THC‐morphine . Psychotropic and somatic side‐effects ( sleepiness , euphoria , anxiety , confusion , nausea , dizziness , etc . ) were common , but usually mild", "OBJECTIVE The ability to accurately identify articles about therapy in large bibliographic data bases such as EMBASE is important for research ers and clinicians . Our study aim ed to develop optimal search strategies for detecting sound treatment studies in EMBASE in the year 2000 . METHODS H and search es of journals were compared with retrievals from EMBASE for c and i date search strategies . Six trained research assistants review ed fifty-five journals indexed in EMBASE and rated articles using purpose and quality indicators . C and i date search strategies were developed for identifying treatment articles and then tested , and the retrievals were compared with the h and - search data . The operating characteristics of the strategies were calculated . RESULTS Three thous and eight hundred fifty articles were original studies on treatment , of which 1,256 ( 32.6 % ) were method ologically sound . Combining search terms revealed a top performing strategy ( r and om:.tw . OR clinical trial:.mp . OR exp health care quality ) with sensitivity of 98.9 % and specificity of 72.0 % . Maximizing specificity , a top performing strategy ( double-blind:.mp . OR placebo:.tw . OR blind : .tw . ) achieved a value over 96.0 % , but with compromised sensitivity at 51.7 % . A 3-term strategy achieved the best optimization of sensitivity and specificity ( r and om:.tw . OR placebo:.mp . OR double-blind:.tw . ) , with both these values over 92.0 % . CONCLUSION Search strategies can achieve high performance for retrieving sound treatment studies in EMBASE", "This paper describes PEDro , the Physiotherapy Evidence Data base . PEDro is a web-based data base of r and omized controlled trials and systematic review s in physiotherapy . It can be accessed free of charge at http://ptwww.cchs.usyd.edu.au/pedro . The data base contains bibliographic details and abstract s of most English- language r and omized trials and systematic review s in physiotherapy , and of many trials and review s in other language s. Trials on the data base are rated on the basis of their method ological quality so that users of the data base can quickly identify trials of high quality . Trials and systematic review s are extensively indexed to facilitate search ing . PEDro provides an important information re source to support evidence -based clinical practice", " Twenty-six men participated in a study of pain and sensation thresholds and pain tolerance . Cutaneous electrical stimulation was applied to the subjects ’ fingers and thresholds were determined before and after smoking marihuana . It was found that marihuana affected thresholds by increasing sensitivity to both painful and nonpainful stimulation and reducing tolerance for pain", "OBJECTIVE In this study , we explored the analgesic and antihyperalgesic properties of a synthetic cannabinoid ( nabilone ) on experimental heat pain in men and women , as well as its effects on descending pain inhibitory systems . RESEARCH DESIGN AND METHODS A double-blind , placebo controlled , crossover study of nabilone single doses of 0.5 and 1 mg was conducted . Excitatory systems were elicited using a temporal summation test ( tonic heat pain evoked by a Peltier thermode ) administered before and after activation of descending inhibitory control ( triggered using a counter-irritation procedure ) . These tests were given before and after drug treatment . Primary outcome measures included average heat pain , temporal summation of heat pain , and drug-induced changes in the strength of descending analgesia . Possible adverse reactions were monitored throughout treatment . Seven men ( mean age = 22.5 years , SD = + /- 1.5 ) and 10 women ( mean age = 23.2 years , SD = + /- 2.8 ) completed this study . RESULTS Nabilone ( 1 mg and 0.5 mg ) did not reduce the global pain intensity experienced during tonic heat pain ( all values of p > 0.18 ) . It also failed to potentiate the strength of descending inhibitory responses ( all values of p > 43 ) . Nevertheless , at the highest dose ( 1 mg ) , and only for women , nabilone significantly ( p = 0.003 ) dampened the temporal summation experienced during the last portion of the tonic heat pulse test ( i.e. , the period of time during which temporal summation is greatest ) . This antihyperalgesic effect was not observed for men ( at either 0.5 mg or 1 mg dose ) , suggesting that the antihyperalgesic properties of cannabinoids are greater for women than for men . Adverse reactions encountered were generally mild and did not provoke the cessation of testing . CONCLUSIONS Nabilone failed to produce analgesic effects and it did not interact with descending pain inhibitory systems . However , we found that a single 1 mg dose of nabilone reduced temporal summation for women but not men . Although a titration regime and a larger sample of subjects might have provided more robust effects , these preliminary results suggest that nabilone appears effective at relieving hyperalgesic responses in women . Possible neurobiological mechanisms and clinical implication s are further discussed" ]	41189636-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Ankylosing spondylitis ( AS ) is a chronic inflammatory disease of unknown cause and affects mainly the spine , but can also affect other joints . Disease progression may result in loss of mobility and function . Sulfasalazine is a disease-modifying antirheumatic drug used in the treatment of AS . However , its efficacy remains unclear . This is an up date of a Cochrane review first published in 2005 . OBJECTIVES To evaluate the benefits and harms of sulfasalazine for the treatment of ankylosing spondylitis ( AS ) . SEARCH METHODS We search ed for relevant r and omized and quasi-r and omized trials in any language , using the following sources : the Cochrane Central Register of Controlled Trials ( CENTRAL ) ( The Cochrane Library 2013 , Issue 11 ) ; MEDLINE ( 2003 to 28 November 2013 ) ; EMBASE ( 2003 to 27 November 2013 ) ; CINAHL ( 2003 to 28 November 2013 ) ; Ovid MEDLINE data , World Health Organization International Clinical Trials Registry Platform ( 28 November 2013 ) ; and the reference sections of retrieved articles . SELECTION CRITERIA We evaluated r and omized and quasi-r and omized trials examining the benefits and harms of sulfasalazine on AS . DATA COLLECTION AND ANALYSIS Two review authors independently review ed unblinded trial reports according to the selection criteria . Disagreements on the inclusion of the studies were resolved , when necessary , by recourse to a third review author . The same authors independently assessed the risk of bias of included trials and entered the data extracted from the included trials . We combined results using mean difference ( MD ) or st and ardised mean difference ( SMD ) for continuous data , and risk ratio ( RR ) for dichotomous data .We restructured outcome measures for this up date based on recommendations from the editorial group . Major outcomes included : pain , Bath ankylosing spondylitis disease activity index ( BASDAI ) , Bath ankylosing spondylitis function index ( BASFI ) , Bath ankylosing spondylitis metrology index ( BASMI ) , radiographic progression , total number of withdrawals due to adverse events , and serious adverse events . MAIN RESULTS We did not add any new studies to this review following the up date d search . In the original review , we included 11 studies in the analysis , involving 895 participants in total . All included studies compared sulfasalazine with placebo . We judged most of the studies as low risk of bias or unclear risk of bias in five domains ( r and om sequence generation , allocation concealment , blinding of outcome assessment , selective reporting , and other sources of bias ) . However , for incomplete outcome data , we only judged one trial at low risk of bias . None of the included trials assessed BASDAI , BASFI , BASMI or radiographic progression . Different parameters were used to assess pain . The pooled MD for back pain measured on a 0 to 100 mm visual analogue scale was -2.96 ( 95 % confidence interval ( CI ) -6.33 to 0.41 ; absolute risk difference 3 % , 95 % CI 1 % to 6 % ; 6 trials ) . Compared to placebo , a significantly higher rate of withdrawals due to adverse effects ( RR 1.50 , 95 % CI 1.04 to 2.15 ; absolute risk difference 4 % , 95 % CI 0.4 % to 8.8 % ; 11 trials ) was found in the sulfasalazine group . A serious adverse reaction was reported in one patient taking sulfasalazine ( Peto odds ratio 7.50 , 95 % CI 0.15 to 378.16 ) . AUTHORS ' CONCLUSIONS There is not enough evidence to support any benefit of sulfasalazine in reducing pain , disease activity , radiographic progression , or improving physical function and spinal mobility in the treatment of AS . A statistically significant benefit in reducing the erythrocyte sedimentation rate and easing spinal stiffness was mentioned in the previous version . However , the effect size was very small and not clinical ly meaningful . More withdrawals because of side effects occurred with sulfasalazine . Further studies , with larger sample sizes , longer duration , and using vali date d outcome measures are needed to verify the uncertainty of sulfasalazine in AS	[ "OBJECTIVE To make a longitudinal study of antibodies to Klebsiella pneumoniae in patients with ankylosing spondylitis ( AS ) and to assess treatment effects . As a comparison we measured antibodies of 2 other gut associated bacteria , Escherichia coli and Proteus mirabilis . METHODS In a double blind study in 84 Finnish out patients with AS before and after 26 weeks ' treatment with sulfasalazine or placebo we measured serum antibodies to Klebsiella pneumoniae , E. coli and Proteus mirabilis with ELISA : Serum sample s of 100 healthy blood donors served as controls . RESULTS The levels of IgA class antibodies to all 3 bacteria were statistically significantly higher in the sera of the patients compared to the controls . During sulfasalazine treatment significant decreases were observed in concentrations of the IgA class antibodies to Klebsiella and E. coli whereas only a slight decrease was observed in the concentrations of IgA antibodies to Proteus mirabilis . There were no correlations between the clinical and laboratory results observed with sulfasalazine and decrease in concentrations of IgA class antibodies . CONCLUSION Our results agree with the role of gut associated lymphoid tissue in the pathogenesis of AS , but do not totally exclude Klebsiella pneumoniae as a specific agent contributing to the development of AS", "In recent years sulphasalazine has gained acceptance as an effective agent for the treatment of rheumatoid arthritis . Ankylosing spondylitis is a disease where remission inducing drugs so far have been lacking . In this double blind trial sulphasalazine was compared with placebo in 37 patients with ankylosing spondylitis . Evaluation after three months ' treatment showed reduction of inflammatory activity and improvement of clinical variables . The side effects were mild . The results suggest that sulphasalazine is a potentially effective and safe drug in the treatment of ankylosing spondylitis", "OBJECTIVE To compare the efficacy of sulfasalazine ( SSZ ) with its two moieties , 5-aminosalicylic acid ( ASA ) and sulfapyridine ( SP ) , in patients with active ankylosing spondylitis ( AS ) . METHODS A 26-week r and omized , observer-blinded , 2-center , controlled study of treatment with either SSZ , ASA , or SP was conducted in 90 patients with active AS . Patients were evaluated at baseline and at monthly intervals , using several clinical and laboratory measures of disease activity . A global assessment of treatment efficacy was made by both patients and observers at the end of the study period . RESULTS There were no significant changes in any of the parameters of disease activity in the ASA treatment group . Levels of serum IgG , IgA , and IgM fell significantly during treatment with SP , but none of the other changes reached statistical significance . Plasma viscosity and IgG and IgA levels fell significantly during treatment with SSZ , as did nocturnal spinal pain and overall spinal pain . Patients and observers reported a favorable outcome after treatment with SSZ or SP significantly more often than with ASA treatment . CONCLUSION SP appears to be the active moiety in AS , although there was a trend suggesting a better outcome in the SSZ group compared with the SP group , perhaps suggesting the importance of a common sulfonamide structure for efficacy", "OBJECTIVES To assess the effect of sulfasalazine ( SSZ ) on inflammatory back pain ( IBP ) due to active undifferentiated spondyloarthritis ( uSpA ) or ankylosing spondylitis in patients with symptom duration METHODS Patients with IBP and a Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) > 3 from 12 centres were r and omly assigned to 24 weeks ' treatment with SSZ 2 g/day or placebo . The primary outcome variable was the change in BASDAI over 6 months . Secondary outcomes included measures of spinal pain , physical function and inflammation . RESULTS 230 patients ( 50 % men , age range 18 - 64 years , 67 % human leucocyte antigen B27 positive ) were treated with either SSZ 2x1 g/day or placebo for 6 months . Enthesitis was found in 50 % , and peripheral arthritis in 47 % of the patients . The mean ( SD ) BASDAI dropped markedly in both groups : by 3.7 ( 2.7 ) and 3.8 ( 2.4 ) , respectively , as did most secondary outcome measures . No noticeable difference in treatment was observed between groups . Patients with IBP and no peripheral arthritis had significantly ( p = 0.03 ) more benefit with SSZ ( BASDAI 5.1 ( 1.3 ) to 2.8 ( 2.3 ) ) than with placebo ( 5.2 ( 1.6 ) to 3.8 ( 2.4 ) ) . Spinal pain ( p = 0.03 ) and morning stiffness ( p = 0.05 ) improved with SSZ in these patients , but other secondary outcomes were not markedly different . CONCLUSION SSZ was no better than placebo for the treatment of the signs and symptoms of uSpA ; however , SSZ was more effective than placebo in the subgroup of patients with IBP and no peripheral arthritis ", "OBJECTIVE To determine if the peripheral articular manifestations of the seronegative spondylarthropathies ( SNSA ) respond differently than the axial manifestations to treatment with sulfasalazine ( SSZ ) . METHODS This is a re analysis of a previously reported series of r and omized , double-blind , placebo-controlled , multicenter trials comparing the effects of SSZ , 2,000 mg/day , and placebo on the axial and peripheral articular manifestations of ankylosing spondylitis ( AS ) , psoriatic arthritis ( PsA ) , and reactive arthritis ( ReA ; Reiter 's syndrome ) . Patients were classified as treatment responders on the basis of meeting predefined improvement criteria in 4 outcome measures : namely , patient and physician global assessment s in all patients , morning stiffness and back pain in patients with axial manifestations , and joint pain/tenderness scores and joint swelling scores in patients with peripheral articular manifestations . RESULTS Six hundred nineteen SNSA patients ( 264 AS , 221 PsA , and 134 ReA ) were studied . One hundred eighty-seven of these patients had only axial manifestations of their disease , while 432 patients had peripheral articular manifestations . Of the patients with axial disease , 40.2 % of the SSZ group and 43.3 % of the placebo group met the predefined response criteria ( P = 0.67 ) . Of the peripheral articular group , 59.0 % of the SSZ-treated patients and 42.7 % of the placebo-treated patients showed a response ( P = 0.0007 ) . CONCLUSION In a large group of affected individuals , the response of SNSA patients to SSZ appears to be related to the articular manifestations of their disease . These data demonstrate that the axial and peripheral articular manifestations of SNSA respond differently to treatment with SSZ . In SNSA patients with persistently active peripheral arthritis , SSZ is safe , well tolerated , and effective", "The efficacy of salazosulfapyridine ( SI ) has been recently reported in the course of peripheral arthritis in ankylosing spondylarthritis ( SPA ) , but is action on the axial forms of the disease was not known . We have therefore conducted a therapeutic trial in 60 patients suffering from SPA , without peripheral involvement clinical sign evoking an enterocolopathy . This double-blind study compared the activity of SI at a dose of 2 g/day with a placebo , for 6 months . Thirteen patients had to discontinue the treatment : 6 in the placebo group ( inefficacy : 3 cases , anemia : 1 case , epigastric pain : 1 case , rash : 1 case ) and 7 cases in the SI group ( inefficacy : 2 cases , nauseous : 3 cases , abdominal pain : 1 case , moderate elevation of transaminases : 1 case ) . These 13 patients were kept for the global analysis and considered as therapeutic failures . The treatment was considered effective in 15 out of 30 patients of group SI and in 30 patients on placebo ( p less than 0.02 ) . In addition , in group SI , a statistically significant decrease of the daily dose of non-steroid anti-inflammatory drugs was observed ( -6.5 + /- 7.2 versus -2.4 + /- 6.4 in the placebo group , p less than 0.05 ) ; also was observed a decrease of the functional index ( -5.9 + /- 6.6 versus -1.9 + /- 5.7 in the group placebo , p less than 0.05 ) and of the serum level of immunoglobulin G ( -1.8 + /- 3.6 g/l versus + 0.8 + /- 2.9 in the placebo group , p less than 0.025 ) . ( ABSTRACT TRUNCATED AT 250 WORDS", "BACKGROUND There are few effective treatments for ankylosing spondylitis , which causes substantial morbidity . Because of the central role of tumor necrosis factor alpha in the spondyloarthritides , we performed a r and omized , double-blind , placebo-controlled trial of etanercept , a recombinant human tumor necrosis factor receptor (p75):Fc fusion protein , in patients with ankylosing spondylitis . METHODS Forty patients with active , inflammatory ankylosing spondylitis were r and omly assigned to receive twice-weekly subcutaneous injections of etanercept ( 25 mg ) or placebo for four months . The primary end point was a composite of improvements in measures of morning stiffness , spinal pain , functioning , the patient 's global assessment of disease activity , and joint swelling . Patients were allowed to continue taking nonsteroidal antiinflammatory drugs , oral corticosteriods ( disease-modifying antirheumatic drugs at stable doses during the trial . RESULTS Treatment with etanercept result ed in significant and sustained improvement . At four months , 80 percent of the patients in the etanercept group had a treatment response , as compared with 30 percent of those in the placebo group ( P=0.004 ) . Improvements over base-line values for various measures of disease activity , including morning stiffness , spinal pain , functioning , quality of life , enthesitis , chest expansion , erythrocyte sedimentation rate , and C-reactive protein , were significantly greater in the etanercept group . Longitudinal analysis showed that the treatment response was rapid and did not diminish over time . Etanercept was well tolerated , with no significant differences in rates of adverse events between the two groups . CONCLUSIONS Treatment with etanercept for four months result ed in rapid , significant , and sustained improvement in patients with ankylosing spondylitis", "UNLABELLED BACKGROUND Treatment options for patients with ankylosing spondylitis are few . We aim ed to assess the effectiveness of infliximab , an antibody to tumour necrosis factor (TNF)-alpha , in treatment of such patients . METHODS In this 12-week placebo-controlled multicentre study , we r and omly assigned 35 patients with active ankylosing spondylitis to intravenous infliximab ( 5 mg/kg ) and 35 to placebo at weeks 0 , 2 , and 6 . One patient in the infliximab group was withdrawn from the study . Our primary outcome was regression of disease activity of at least 50 % . To assess response , we used vali date d clinical criteria from the ankylosing spondylitis assessment working group , including disease activity ( BASDAI ) , functional indices ( BASFI ) , metrology ( BASMI ) , and quality of life ( short form 36 ) . Analyses were done by intention to treat . FINDINGS 18 ( 53 % ) of 34 patients on infliximab had a regression of disease activity at week 12 of at least 50 % compared with three ( 9 % ) of 35 on placebo ( difference 44 % [ 95 % CI 23 - 61 ] , p Function and quality of life also improved significantly on infliximab but not on placebo ( p infliximab was generally well tolerated , but three patients had to stop treatment because of systemic tuberculosis , allergic granulomatosis of the lung , or mild leucopenia . INTERPRETATION Our results show that treatment with infliximab is effective in patients with active ankylosing spondylitis . Since there are some potentially serious adverse effects , we recommend that this treatment mainly be used in co-operation with rheumatological centres", "Summary In a 12-month double-blind placebo-controlled trial , the effect of sulphasalazine was studied in 40 patients with ankylosing spondylitis . The treatment group showed significant improvement in pain , stiffness , sleep disturbance ( p finger/floor distance , erythrocyte sedimentation rate , C-reactive protein , orosomucoid and IgA levels ( p sleep disturbance ( p finger/floor distance and erythrocyte sedimentation rate ( p Sulphasalazine did not retard radiological progression as measured either by plain X-ray or computerised tomographic scans . Multiple analysis of variance did not show a significant difference in disease activity indicators between the 2 groups", "OBJECTIVE To determine whether sulfasalazine ( SSZ ) at a dosage of 2,000 mg/day is effective for the treatment of active ankylosing spondylitis ( AS ) that is not controlled with nonsteroidal antiinflammatory drug therapy . METHODS Two hundred sixty-four patients with AS were recruited from 15 clinics , r and omized ( double-blind ) to SSZ or placebo treatment , and followed up for 36 weeks . Treatment response was based on morning stiffness , back pain , and physician and patient global assessment s. RESULTS While longitudinal analysis revealed a trend favoring SSZ in the middle of treatment , no difference was seen at the end of treatment . Response rates were 38.2 % for SSZ and 36.1 % for placebo ( P = 0.73 ) . The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo ( P SSZ ( P = 0.02 ) . Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints . CONCLUSION SSZ at a dosage of 2,000 mg/day does not seem to be more effective than placebo in the treatment of AS patients with chronic , longst and ing disease . SSZ is well tolerated and may be more effective than placebo in the treatment of AS patients with peripheral joint involvement . This effect is more pronounced in treatment of the peripheral arthritis in this subgroup of AS patients", "OBJECTIVE To confirm in a placebo-controlled trial the safety and efficacy profile of infliximab in short-term treatment of patients with active spondylarthropathy ( SpA ) . METHODS Forty patients with active SpA were r and omly assigned to receive an intravenous loading dose ( weeks 0 , 2 , and 6 ) of 5 mg/kg infliximab or placebo . Evaluations for efficacy and safety were performed at weeks 1 , 2 , 6 , 8 , and 12 . The primary end points of this study were the improvements in patient and physician global assessment s of disease activity on a 100-mm visual analog scale . RESULTS Both primary end points improved significantly in the infliximab group compared with the baseline value , with no improvement in the placebo group . As early as week 2 and sustained up to week 12 , there was a highly statistically significant difference between the values for these 2 end points in the infliximab versus the placebo group . In most of the other assessment s of disease activity ( laboratory measures , assessment s of specific peripheral and /or axial disease ) , significant improvements were observed in the infliximab group compared with the baseline value and compared with placebo . Minor adverse events not causing discontinuation were equally observed in both treatment groups . There was one severe drug-related adverse event , in which a patient developed disseminated tuberculosis . CONCLUSION Tumor necrosis factor alpha blockade with infliximab in patients with active SpA was well tolerated and result ed in significant clinical and laboratory improvements in this short-term , placebo-controlled study . However , the occurrence of tuberculosis in one patient necessitates strict inclusion criteria and long-term followup", "A 3-year placebo-controlled trial of sulphasalazine ( SASP ) in 89 patients with established AS ( including radiological sacroiliitis ) showed a reduced frequency of peripheral arthritis in the treated group but did not show any definite benefit in the maintenance of spinal mobility . Adverse effects causing treatment withdrawal occurred in five placebo-treated patients and eight SASP-treated patients , but 22 patients preferred to stop taking daily medication of unproven benefit for the full 3 years . The natural history of established AS suggested two groups of patients : the majority with principally spinal symptoms and infrequent peripheral arthritis or iritis , and a minority who tend to have recurrent extra-spinal problems", "OBJECTIVE Etanercept , a fully human tumor necrosis factor ( TNF ) receptor , is an effective treatment in patients with ankylosing spondylitis ( AS ) . Sulfasalazine is frequently used for the treatment of both axial symptoms and peripheral symptoms of AS , and it has been the recommended therapy before the use of an anti-TNF agent when peripheral arthritis is present . Until now , no clinical trial has compared the efficacy and safety of a TNF blocker with that of sulfasalazine . This study was undertaken to compare the efficacy and safety of etanercept with that of sulfasalazine after 16 weeks of treatment in patients with axial and peripheral manifestations of AS . METHODS In this r and omized , double-blind study , patients received etanercept 50 mg once weekly ( n=379 ) or sulfasalazine titrated to a maximum of 3 gm/day ( n=187 ) for 16 weeks . The primary end point was the proportion of patients who achieved the Assessment of SpondyloArthritis international Society criteria for 20 % improvement ( ASAS20 ) at 16 weeks . Last observation carried forward was predefined for imputation of missing values . RESULTS The mean age of the patients was 41 years , 74 % were male , and the mean disease duration was 7.6 years . The proportion of ASAS20 responders at week 16 was greater among patients treated with etanercept compared with those treated with sulfasalazine ( 75.9 % versus 52.9 % ; P etanercept was found to be more effective than sulfasalazine ( P the axial symptoms and peripheral manifestations . Serious adverse events rarely occurred , and the rate of serious adverse events did not differ between groups . CONCLUSION In this population of patients with AS , etanercept was significantly more effective than sulfasalazine in improving the signs and symptoms of AS in the axial skeleton and peripheral joints", "Serum levels of immunoglobulin A ( IgA ) and the complex immunoglobulin A-alpha 1 antitrypsin ( IgA-alpha 1AT ) were measured at the commencement and after 3 months of a double-blind , placebo-controlled trial of sulphasalazine ( SAS ) in patients with active ankylosing spondylitis ( AS ) . Twenty-eight patients were evaluated , 15 on sulphasalazine , 13 on placebo . Significant falls were seen in both IgA ( p less than 0.01 ) and IgA-alpha 1AT ( p less than 0.001 ) in the actively treated patients . In addition , significant improvement in clinical and laboratory measures of disease were observed . It is concluded that SAS is effective in AS and modulates the immune response", "Purpose : To assess the effects of sulfasalazine in preventing recurrences and reducing the severity of anterior uveitis associated with ankylosing spondylitis and chronic intestinal inflammation . Methods : Twenty-two patients with anterior uveitis associated with ankylosing spondylitis were studied . Ten patients were r and omised to receive oral sulfasalazine ( group 1 ) and 12 patients r and omised to no treatment ( group 2 ) ; all were followed for 3 years . Blood-aqueous barrier permeability was determined by fluorophotometry and bowel biopsies were taken . Results : A statistically significant difference was observed between the two groups regarding the number of recurrences of uveitis ( p = 0.016 ) . The blood-aqueous barrier permeability was significantly higher during acute attacks in group 2 ( group 1 : 31.3 ± 26.4 × 10−4 min−1 vs group 2 : 66.2 ± 28.5 × 10−4 min−1 ; p = 0.019 ) but not during the disease-free period . We observed a higher incidence of chronic intestinal inflammation at the end of the study in group 2 ( group 1 : 3/8 vs group 2 : 7/9 , p = 0.153 ) . No relation was observed between blood-aqueous barrier permeability and the number of recurrences . The number of patients with severe persistent posterior synechiae at the end of the study was higher in group 2 ( group 1 : 4 patients before and 4 patients at the end ; group 2 : 4 patients before and 8 patients at the end ; p = 0.65 ) . Conclusion : Sulfasalazine may be beneficial in preventing recurrences and reducing the severity of anterior uveitis associated with ankylosing spondylitis", "Ninety-five patients with ankylosing spondylitis received either sulphasalazine ( less than or equal to 3 g/day ) or placebo for 24 weeks . The patients who received sulphasalazine showed significantly improved clinical parameters [ duration of morning stiffness ( p less than 0.05 ) , the number of painful and swollen joints ( less than 0.05 ) ] and laboratory parameters [ erythrocyte sedimentation rate ( p less than 0.001 ) , haptoglobin ( p less than 0.05 ) , IgG ( p less than 0.05 ) , IgA ( p less than 0.001 ) , IgM ( p less than 0.05 ) ] . No statistically significant differences were seen in the patients receiving placebo . The results suggest that sulphasalazine is effective for the treatment of patients with ankylosing spondylitis . In these patients , there was also a diminution of the daily dosage of nonsteroidal antiinflammatory drugs . In the majority of patients , clinical and laboratory improvements were expressed more pronouncedly in the peripheral form of ankylosing spondylitis than in the axial form , but statistically no significant differences were found between the two groups", "OBJECTIVE To assess the impact of ankylosing spondylitis ( AS ) on patient health-related quality of life ( HRQOL ) relative to both the general US and chronically-ill population s , and to evaluate whether etanercept therapy can reverse impairments in HRQOL due to AS . METHODS Two AS patient population s were evaluated : patients with AS from a US clinical trial who were r and omized to receive either etanercept ( n = 20 ) or placebo ( n = 20 ) for 16 weeks , and placebo-treated patients from a multinational sample who subsequently received etanercept ( n = 129 ) during a 48-week , open-label extension study . A sample from the US general population and patients with other medical conditions derived from the National Survey of Functional Health Status were used as comparators to evaluate the relative impact of active AS on HRQOL , as measured by the Short Form 36 ( SF-36 ) question naire . RESULTS At baseline , patients with AS in both the US and multinational sample s had significantly lower scores than the US general population on all 8 SF-36 scales . Compared with patients with other medical conditions , patients with AS had the lowest scores in the physical domains -- Physical Functioning , Role Physical , and Bodily Pain . Impairments in SF-36 scores for psychosocial domains , such as Social Functioning , Role Emotional , and Mental Health , were somewhat less pronounced in patients with AS . Treatment with etanercept significantly improved the HRQOL of patients with AS on all 8 SF-36 scales , especially in the same physical domains that showed the greatest impairments prior to treatment ( Physical Functioning , Role Physical , and Bodily Pain ) . CONCLUSION Patients with active AS despite conventional therapy have significantly reduced HRQOL across a wide range of domains . These reductions are most pronounced in the physical domains and exceed those seen in many other chronic diseases . Etanercept therapy significantly improves patient HRQOL , indicating that decrements in HRQOL due to AS may be at least partly reversible", " Sixty-two patients with long established but symptomatic ankylosing spondylitis were treated with sulphasalazine or matching placebo in a r and omized double-blind controlled trial for 48 weeks . There were no consistent significant differences between the treatment groups in clinical parameters despite multiple assessment s. Equivalent numbers in each group were able to decrease or stop non-steroidal anti-inflammatory drug ingestion during the study period ( four active , eight placebo ) . Side effects were reported more commonly in the sulphasalazine group ( 27 versus 17 , NS ) , but only 21 patients stopped treatment because of side effects ( 12 versus 9 , NS ) . Analysis of the subgroup with an initial ESR greater than 20 mm/h failed to show any persisting differences of response between sulphasalazine and placebo . We conclude that sulphasalazine therapy does not have a role in the treatment of chronic ankylosing spondylitis", "Sulphasalazine has been reported to be effective in ankylosing spondylitis with peripheral arthritis , but its efficacy in spondylitis is unknown . Thus 60 patients with active ankylosing spondylitis without peripheral arthritis or gastrointestinal symptoms were r and omly allocated to one of two therapeutic groups . One group received 2 g sulphasalazine daily for six months and the other a placebo . Thirteen patients ( six given placebo and seven given sulphasalazine ) dropped out of the trial and were considered to be treatment failures . After six months ' follow up efficacy was rated as good or very good by 15 of the 30 patients given sulphasalazine and by only six of the 30 given placebo ( p less than 0.02 ) . Furthermore , in the patients given sulphasalazine the daily consumption of non-steroidal anti-inflammatory drugs , functional index , and plasma IgG concentrations had fallen significantly . These data suggest that sulphasalazine may be a safe and effective treatment for spondylitis in ankylosing spondylitis", "OBJECTIVE To describe the characteristics of enthesitis and arthritis in the active inflammatory stage of juvenile onset spondyloarthropathies ( SpA ) during a short-term follow-up . PATIENTS AND METHODS The study group included data of 33 patients with juvenile-onset SpA with enthesitis in > or = 3 sites , arthritis in > or = 4 joints , and erythrocyte sedimentation rate ( ESR ) of > or = 25 mm/h despite treatment , who participated in a 26-week , double-blind , sulfasalazine versus placebo trial that showed no significant differences between groups in regard to enthesitis and arthritis . RESULTS Twenty-seven boys and 6 girls ( mean age : 15.3 + /- 3.5 years ; mean disease duration : 4.1 + /- 2.7 years ) with the seronegative enthesopathy and arthropathy ( SEA ) syndrome ( n = 20 ) or ankylosing spondylitis ( AS ; n = 13 ) comprised the group . Throughout the study , the mean ( + /- SD ) number of swollen joints and tender entheses were 4.6 + /- 2.5 and 8.3 + /- 5.4 . The entheses and joints most frequently involved were the calcaneal attachments of the plantar fascia ( 87.9 % ) and Achilles tendon ( 81.8 % ) and the ankle ( 87.9 % ) and knee ( 72.7 % ) , respectively . There was pain in the cervical , thoracic , and lumbar spine in 39.4 % , 69.7 % , and 63.6 % of patients and in the sacroiliac joints in 48.5 % . Mid-foot involvement ( or tarsitis ) occurred in 29 patients ( 87.9 % ) . Except for the feet , the simultaneous occurrence of enthesitis and arthritis in other sites was rare . Overall , there were no significant differences between SEA syndrome and AS patients . CONCLUSIONS Disease activity shows a significant trend for entheses and joints of the feet and a significant prevalence of axial enthesitis in juvenile onset SpA. Mid-foot involvement appears to be the most characteristic and potentially , the most severe form of disease in these patients", "OBJECTIVE To develop and compare c and i date improvement criteria for anti-TNFalpha treatment in ankylosing spondylitis with optimal discriminating capacity between treatment and placebo . METHODS Data from two r and omised controlled trials which included 99 patients treated with infliximab or etanercept were used to evaluate 50 c and i date improvement criteria . These were developed on the basis of pain , patient 's global assessment , function , morning stiffness , spinal mobility , and C reactive protein . Different levels of improvement in each domain ( 20 - 60 % ) were used to define Boolean type criteria . These criteria were compared with different percentages of improvement on the BASDAI and with modified ASAS improvement criteria . Bootstrap methods were applied to calculate 95 % confidence intervals ( CI ) of the chi(2 ) test values to select the best c and i date improvement criteria . RESULTS The best performing improvement criteria were \" 20 % improvement in five of six domains \" ( chi(2 ) = 31.9 ( 95 % CI , 18.0 to 46.9 ) ) with a low placebo response of 2.9 % and a high response to infliximab of 67.7 % ; and \" ASAS 40 % improvement \" ( chi(2 ) = 26.5 ( 13.3 to 41.1 ) ) , with response to placebo of 5.7 % and response to infliximab of 64.7 % . The good discriminating capacity of the two improvement criteria was confirmed by the combined data set of the infliximab and etanercept trial . CONCLUSIONS The \" five of six \" improvement criterion has the advantage of including the objective domains spinal mobility and acute phase reactants , but requires only 20 % improvement . The ASAS 40 % improvement criterion has the advantage of setting a high threshold , but only in patient reported outcomes . The choice between these improvement criteria needs to be based on further validation from upcoming trials", "OBJECTIVE To develop criteria for symptomatic improvement in patients with ankylosing spondylitis ( AS ) , using outcome domain data from placebo-controlled clinical trials of nonsteroidal antiinflammatory drugs ( NSAIDs ) . METHODS Patient data from 5 short-term , r and omized , controlled trials were used to assess equivalence , reliability , and responsiveness of multiple items in the 5 outcome domains for AS treatment : physical function , pain , spinal mobility , patient global assessment , and inflammation . At least one measure per domain was responsive ( st and ardized response mean of > 0.5 ) , except for the spinal mobility domain , which was omitted from the criteria . We developed and tested c and i date improvement criteria in a r and om two-thirds subset from the 3 largest trials and used the remaining one-third for validation . These 3 largest trials included 923 patients ( 631 receiving NSAIDs , 292 in placebo groups ) . We selected the multiple domain definition that best distinguished NSAID treatment from placebo by chi-square test and that had a placebo response rate of single domains and in multiple measure indices , as well as combinations of improvements in multiple domains . Worsening in a domain was defined as a change for the worse of > or = 20 % and a net change for the worse of > or = 10 units on a scale of 0 - 100 . Partial remission ( for comparison purpose s ) was defined as an end-of-trial value of or = 20 % and > or = 10 units in each of 3 domains and absence of worsening in the fourth discriminated best in the development subset ( 51 % of patients improved with NSAIDs , 25 % with placebo ; chi2 = 36.4 , P partial disease remission at the end of the trial had also improved by this criterion . Among all 923 patients , improvement rates using this criterion were 49 % for NSAID-treated patients and 24 % for placebo-treated patients . CONCLUSION Although further validation using data from new trials is still needed , we conclude that we have developed a clinical ly valid , easy-to-use measure of short-term improvement in AS", "OBJECTIVE To assess the efficacy and tolerability of sulfasalazine ( SSZ ) in the treatment of spondylarthropathy . METHODS We conducted a 6-month r and omized , placebo-controlled , double-blind , multicenter study of patients with spondylarthropathy whose disease had remained active despite treatment with nonsteroidal antiinflammatory drugs . Patients were treated with SSZ ( 3 gm/day ) or placebo . The primary efficacy variables were the physician 's and patient 's overall assessment s , pain , and morning stiffness . End points were analyzed in the intent-to-treat and completer patient population s ; the time course of effect was analyzed in the completer patient population . RESULTS Of the 351 patients enrolled , 263 ( 75 % ) completed the 6-month treatment period . The withdrawal rates were 35 ( 20 % ) and 53 ( 30 % ) in the placebo and SSZ groups , respectively . In the intent-to-treat analysis of end point efficacy , the between-treatment difference reached statistical significance only for 1 of the 4 primary outcome variables , the patient 's overall assessment of disease activity , for which 60 % of the patients taking SSZ improved by at least 1 point on a 5-point scale , in contrast to 44 % of the patients taking placebo . Laboratory markers of inflammation also showed statistically significant change in favor of SSZ . In subgroup analysis , the most impressive effects were seen in patients with psoriatic arthritis , both for the 4 primary efficacy variables and for secondary efficacy variables such as the number of inflamed joints . Adverse events were more frequent in the SSZ group than the placebo group , but all were transient or reversible after cessation of treatment . CONCLUSION The results of this study show that SSZ had greater efficacy than placebo in the treatment of active spondylarthropathy , notably in patients with psoriatic arthritis", "Purpose To evaluate the potential of etanercept versus sulfasalazine to reduce active inflammatory lesions on whole-body MRI in active axial spondyloarthritis with a symptom duration of less than 5 years . Methods Patients were r and omly assigned to etanercept ( n=40 ) or sulfasalazine ( n=36 ) treatment over 48 weeks . All patients showed active inflammatory lesions ( bone marrow oedema ) on MRI in either the sacroiliac joints or the spine . MRI was performed at weeks 0 , 24 and 48 and was scored for active inflammatory lesions in sacroiliac joints and the spine including posterior segments and peripheral enthesitis by two radiologists , blinded for treatment arm and MRI time point . Results In the etanercept group , the reduction of the sacroiliac joint score from 7.7 at baseline to 2.0 at week 48 was significantly ( p=0.02 ) larger compared with the sulfasalazine group from 5.4 at baseline to 3.5 at week 48 . A similar difference in the reduction of inflammation was found in the spine from 2.2 to 1.0 in the etanercept group versus from 1.4 to 1.3 in the sulfasalazine group between baseline and week 48 , respectively ( p=0.01 ) . The number of enthesitic sites also improved significantly from 26 to 11 in the etanercept group versus 24 to 26 in the sulfasalazine group ( p=0.04 for difference ) . 50 % of patients reached clinical remission in the etanercept group versus 19 % in the sulfasalazine group at week 48 . Conclusion In patients with early axial spondyloarthritis active inflammatory lesions detected by whole-body MRI improved significantly more in etanercept versus sulfasalazine-treated patients . This effect correlated with a good clinical response in the etanercept group", "Objective . Etanercept , a fully human tumor necrosis factor soluble receptor , is effective in treatment of ankylosing spondylitis ( AS ) . Current guidelines suggest sulfasalazine ( SSZ ) treatment as initial therapy for the management of patients with AS with peripheral arthritis versus therapy with biologics . We compared the efficacy of etanercept with SSZ in patients with AS with peripheral joint involvement . Methods . The efficacy of etanercept 50 mg once weekly was compared with that of SSZ up to 3 g daily in subjects with ≥ 1 swollen peripheral joint at baseline , using data from a 16-week r and omized double-blind study in subjects with AS . Efficacy was assessed by the Assessment in AS criteria and the Bath AS Disease Activity , Functional , and Metrology indices . The last observation carried forward method was used for imputation of missing values . Results . Of 566 subjects included in original study , 181 ( etanercept 121 ; SSZ 60 ) had ≥ 1 swollen peripheral joint and 364 ( etanercept 250 ; SSZ 124 ) had none at baseline . AS patients treated with etanercept showed significantly greater improvement than those treated with SSZ in all joint assessment s regardless of swollen joint involvement . Conclusion . In this analysis , etanercept was significantly more effective than SSZ for management of patients with AS and peripheral joint involvement" ]	41189672-06ff-11f0-808a-c43d1ab1c353
Dynamic sitting has been proposed to reduce low back pain ( LBP ) and /or low back discomfort ( LBD ) while sitting . This is supported by studies suggesting that subjects with LBP assume more static , sustained postures while sitting . This systematic review investigated the effect of dynamic sitting on LBP among subjects with LBP and the development of LBD among pain-free subjects . Electronic data bases were search ed by two independent assessors . All prospect i ve studies which compared the effect of a dynamic sitting condition on LBP or LBD to another sitting condition were eligible , with no minimum follow-up period applied . The quality of the included studies was assessed using the PEDro scale . Seven high- quality studies were eligible , including five crossover studies and two r and omised controlled trials . The results suggest there is currently no evidence to support the use of dynamic sitting as a st and -alone approach in the management of LBP . Practitioner Summary : This systematic review investigated the effect of dynamic sitting on LBP or LBD . Seven high- quality studies met the inclusion and exclusion criteria . Overall , the evidence suggests that dynamic sitting approaches are not effective as a st and -alone management approach for LBP	[ "Low back pain ( LBP ) is the second greatest cause of disability in the USA.1 USA data supports that in spite of an enormous increase in the health re sources spent on LBP disorders , the disability relating to them continues to increase.2 The management of LBP is underpinned by the exponential increase in the use of physical therapies , opiod medications , spinal injections as well as disc replacement and fusion surgery.2 This is maintained by the underlying belief that LBP is fundamentally a patho-anatomical disorder and should be treated within a biomedical model.1 This is in spite of calls over a number of years to adopt a bio-psycho-social approach , and evidence that only 8–15 % of patients with LBP have an identified patho-anatomical diagnosis , result ing in the majority being diagnosed as having non-specific LBP.3 Of this population , a small but significant group becomes chronic and disabled , labelled non-specific chronic low back pain ( NSCLBP ) , consuming a disproportionate amount of healthcare re sources .4 1 . Over the past decade , the traditional biomedical view of LBP has been greatly challenged . This is a result of : the failure of simplistic single-dimensional therapies to show large effects in patients with NSCLBP5–8 ; 2 . the results of clinical trials testing commonly prescribed interventions demonstrating that no management approaches are clearly superior5–7 9 ; 3 . the stories of NSCLBP patients relating their own ongoing pain experiences of multiple failed treatments , conflicting diagnoses , lost hope and ongoing suffering10 ; 4 . the indisputable evidence supporting the multidimensional nature of NSCLBP as a disorder , where disability levels are more closely associated with cognitive and behavioural aspects of pain rather than sensory and biomedical ones11 12 ; 5 . positive outcomes in r and omised controlled trials ( RCTs ) are best predicted by changes in psychological distress , fear avoidance beliefs , self-efficacy in", "Seated work has been shown to constitute a risk factor for low-back pain . This is attributed to the prolonged and monotonous low-level mechanical load imposed by a seated posture . To evaluate the potential health effects with respect to the low back of office chairs with a movable seat and back rest , trunk kinematics , erector spinae EMG , spinal shrinkage and local discomfort were assessed in 10 subjects performing simulated office work . On three separate occasions subjects performed a 3 h task consisting of word processing , computer-aided design and reading . Three chairs were used , one with a fixed seat and back rest and two dynamic chairs , one with a seat and back rest movable in a fixed ratio with respect to each other , and one with a freely movable seat and back rest . Spinal shrinkage measurements showed a larger stature gain when working on the two dynamic chairs as compared with working on the chair with fixed seat and back rest . Trunk kinematics and erector spinae EMG were strongly affected by the task performed but not by the chair type . The results imply that dynamic office chairs offer a potential advantage over fixed chairs , but the effects of the task on the indicators of trunk load investigated were more pronounced than the effects of the chair", "QUESTIONS Does the PEDro scale measure only one construct ie , the method ological quality of clinical trials ? What is the hierarchy of items of the PEDro scale from least to most adhered to ? Is there any effect of year of publication of trials on item adherence ? Are PEDro scale ordinal scores equivalent to interval data ? DESIGN Rasch analysis of two independent sample s of 100 clinical trials from the PEDro data base scored using the PEDro scale . RESULTS Both sample s of PEDro data showed fit to the Rasch model with no item misfit . The PEDro scale item hierarchy was the same in both sample s , ranging from the most adhered to item r and om allocation , to the least adhered to item therapist blinding . There was no differential item functioning by year of publication . Original PEDro ordinal scores were highly correlated with transformed PEDro interval scores ( r = 0.99 ) . CONCLUSION The PEDro scale is a valid measure of the method ological quality of clinical trials . It is valid to sum PEDro scale item scores to obtain a total score that can be treated as interval level measurement and subjected to parametric statistical analysis", "Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists", "Study Design . Prospect i ve cohort study of r and omly selected Veterans Affairs ( VA ) out patients . Objective . To determine the prevalence of magnetic resonance imaging ( MRI ) findings in the lumbar spine among persons without current low back pain or sciatica and to examine which findings are related to age or previous back symptoms . Summary of Background Information . Previous studies of patients without low back pain have not explored the possible association of various MRI findings to past symptoms . Methods . We r and omly selected an age-stratified sample of subjects without low back pain in the past 4 months from clinics at a VA hospital . We collected information on demographics , comorbidity , functional status , and quality of life . MR images were obtained using a st and ardized protocol through each of the five lumbar disc levels . Results . Of 148 subjects , 69 ( 46 % ) had never experienced low back pain . There were 123 subjects ( 83 % ) with moderate to severe desiccation of one or more discs , 95 ( 64 % ) with one or more bulging discs , and 83 ( 56 % ) with loss of disc height . Forty-eight subjects ( 32 % ) had at least one disc protrusion and 9 ( 6 % ) had one or more disc extrusions . Conclusion . Many MR imaging findings have a high prevalence in subjects without low back pain . These findings are therefore of limited diagnostic use . The less common findings of moderate or severe central stenosis , root compression , and extrusions are likely to be diagnostically and clinical ly relevant", "BACKGROUND CONTEXT It is generally recognized that long periods of sitting can either cause or aggravate lumbar pain . A new , ergonomically design ed chair has a fixed backrest and a motor-driven seat with a horizontal rotary movement in alternating left-right cycles . PURPOSE The objective of this study is to prove superiority of the new technique of passive rotary dynamic sitting for subjects working in a sedentary occupation and suffering from lumbar pain . STUDY DESIGN / SETTING A r and omized , double-blind , multicenter , two-armed study was performed using a parallel group design . PATIENT SAMPLE 280 persons suffering from lumbar pain were matched pairwise and r and omized en bloc . OUTCOME MEASURES The first and second primary endpoints target criteria were the vali date d German version of the Oswestry Disability Index ( ODI ) and the number of days of absence from work ( DA ) attributable to lumbar pain , each based on a blinded 2-year follow-up observation after r and omization of the subjects . METHODS After inclusion in the study anonymization , the prob and s were r and omized to receive either an office chair with a motor-driven seat performing a horizontal rotary movement or a chair of the same design without the rotary seat movement . Before delivery of the chairs , 23 prob and s ( 8.2 % ) withdrew their consent to inclusion in the study without stating reasons . From 12 of the remaining matching partners , 23 new pairs were created at r and om , and the study commenced with 124 pairs . RESULTS A further 27 prob and s ( 9.6 % ) were lost to follow-up during the period up to the final consultation . This made it possible to observe the primary endpoint in 82.5 % of the prob and s. The median ODI in both groups was 53 ( 95 % confidence interval for median difference:-1.5 to 0.5 ; p=.59 ) . Median DA in both groups was 0 ( 95 % confidence interval for median difference:-infinity-+infinity ; p=1.00 ) . CONCLUSIONS Under the test conditions used in this study , passive rotary dynamic sitting was not superior to sitting in a high- quality , ergonomically design ed chair not equipped with a micro-rotation function in patients suffering from lumbar pain", "This study compared the effects of sitting with portable supports in either a kyphotic or lordotic posture on low-back and referred pain . Two hundred ten patients with low-back and /or referred pain were r and omly assigned to either a kyphotic posture or lordotic posture group . The kyphotic and lordotic postures were facilitated by the use of a flat foam cushion or lumbar roll , respectively . Pain location , back pain , and leg pain intensity were assessed over a 24–48-hour period under both st and ardized clinical setting s and general sitting environments . When sitting with a lordotic posture , back and leg pain were significantly reduced and referred pain shifted towards the low back . This study demonstrates that in general sitting environments a lumbar roll results in : 1 ) reductions in back and leg pain ; and 2 ) central ization of pain . These findings do not apply to patients with stenosis or spondylolisthesis , whose symptoms may be aggravated by use of a lumbar roll ", "Study Design . Subjective ratings of discomfort were compared between a fixed lumbar support and lumbar support continuous passive motion ( CPM ) device . Objective . To compare a fixed lumbar support with a lumbar support CPM device during prolonged sitting . Summary of Background Data . To prevent low back pain during prolonged sitting , an inflatable lumbar support CPM has been developed . There are no studies that compare static lumbar support with lumbar CPM using the same pressure in the cushions . Methods . A total of 31 male volunteers without low back pain sat in the same chair for a 2-hour period on each of 3 consecutive days under 3 r and omized test methods : 1 , no lumbar support ; 2 , static lumbar support ; and 3 , lumbar support CPM . Each subject rated low back pain , stiffness , fatigue , and buttock numbness on a visual analog scale ( VAS ) . Fixed lumbar support and CPM device were compared with a same inflation pressure in the cushion . For 10 subjects , the whole body posture and the pressure distribution changes of the human-seat interface during CPM were evaluated . Results . Compared with no lumbar support , a significant improvement in VAS scores for low back pain , stiffness , and fatigue was obtained with both static lumbar support and with lumbar support CPM ( P buttock numbness was obtained only with lumbar support CPM . There were no statistical differences in all VAS scores between the fixed lumbar support and the CPM device . A forward rotation of the pelvic region was obtained during inflation of the cushion during CPM . Significant differences ( P CPM device", "BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from \" fair \" to \" substantial , \" and the reliability of the total PEDro score was \" fair \" to \" good .", "Abstract In this study the effect of dynamic stimuli on low back pain during prolonged sitting was investigated . The pain experience of two groups of 60 subjects with aspecific low back pain was recorded . All subjects were investigated on pain behaviour by the Multidimensional Pain Inventory ( MPI ) and pain was measured on an open visual analogue scale ( VAS ) . During sitting , one group received dynamic stimuli that were generated by alternating rotations in the horizontal plane of the seat of the chair , with back and arm rests in fixed position . Two different frequencies of rotation were applied in subgroups . The authors concluded that such stimuli , especially of the lower frequency , reduced pain in prolonged sitting ", "BACKGROUND Prolonged sitting is recognized as a risk factor for the reporting of low back troubles . Despite the use of exercise balls in replacement of the office chair , little quantitative evidence exists to support this practice and hence motivated this research . Given the potential for several biological effects and mechanisms this study was approached with several layers of instrumentation to quantify differences in muscle activation , spine posture , spine compression and stability while sitting on an exercise ball versus a stable seat surface . Also , differences in the pressure distribution at the seat-user interface were quantified for the different seat surfaces to provide an objective perspective on the mechanism influencing perceived comfort levels . METHODS Eight male subjects volunteered to sit for 30 min on an exercise ball and on a wooden stool . Muscle activity and spine position were used to model spine load and stability . An additional seven sat on an exercise ball and chair to examine pressure distribution over the contact area . FINDINGS There was no difference in muscle activation profiles of each of the 14 muscles between sitting on the stool and ball . Calculated stability and compression values showed sitting on the ball made no difference in mean response values . The contact area of the seat-user interface was greatest on the exercise ball . INTERPRETATION The results of this study suggest that prolonged sitting on a dynamic , unstable seat surface does not significantly affect the magnitudes of muscle activation , spine posture , spine loads or overall spine stability . Sitting on a ball appears to spread out the contact area possibly result ing in uncomfortable soft tissue compression perhaps explaining the reported discomfort" ]	411896ae-06ff-11f0-808a-c43d1ab1c353
Background Adult obesity is globally recognized as a public health concern . As adults spend most of their weekdays at work , worksite wellness programs may include topics of nutrition education and physical activity to improve an employee 's body composition . However , results are inconsistent with the impact they have on employees ' body composition . Objective The purpose of this systematic review was to evaluate worksite wellness nutrition and physical activity programs and their subsequent impact on participants ' body composition . Methods Extraction of articles was completed through 4 data bases : PubMed , CINAHL , SCOPUS , and PsycINFO using keywords such as " nutrition and physical activity interventions /programs " and " weight . " A 9-point inclusion criterion was established . Evaluation of the articles was assessed using the Academy of Nutrition and Dietetics Evidence -Based Manual . Results A total of 962 articles were identified . Twenty-three met the inclusion criterion . Seventeen studies result ed in a change in body composition ( e.g. , decreased BMI ( kg/m2 ) , waist circumference , and body fat percentage ) , and six studies did not show any changes . Programs that had professionals frequently interact with participants , regardless if the interactions were done daily , weekly , or monthly , led to a change in body composition . Additionally , programs that incorporated a motivation theory and provided content relevant to participants ' needs result ed in a change in body composition . Conclusion Evidence supports that future worksite wellness programs that are design ed using a motivational theory and content that is created relevant to participants ' needs and that has frequent interactions with participants may result in a change in body composition	[ "This study aims to evaluate the cost-effectiveness of a long-term workplace health promotion programme on physical activity ( PA ) and nutrition . In total , 924 participants enrolled in a 2-year cluster r and omized controlled trial , with departments ( n = 74 ) within companies ( n = 6 ) as the unit of r and omization . The intervention was compared with a st and ard programme consisting of a physical health check with face-to-face advice and personal feedback on a website . The intervention consisted of several additional website functionalities : action-oriented feedback , self-monitoring , possibility to ask questions and monthly e-mail messages . Primary outcomes were meeting the guidelines for PA and fruit and vegetable intake . Secondary outcomes were self-perceived health , obesity , elevated blood pressure , elevated cholesterol level and maximum oxygen uptake . Direct and indirect costs were calculated from a societal perspective , and a process evaluation was performed . Of the 924 participants , 72 % participated in the first and 60 % in the second follow-up . No statistically significant differences were found on primary and secondary outcomes , nor on costs . Average direct costs per participant over the 2-year period were € 376 , and average indirect costs were € 9476 . In conclusion , no additional benefits were found in effects or cost savings . Therefore , the programme in its current form can not be recommended for implementation", "OBJECTIVES We assessed the effects of a worksite multiple-component intervention addressing diet and physical activity on employees ' mean body mass index ( BMI ) and the percentage of employees who were overweight or obese . METHODS This group-r and omized trial ( n = 3799 ) was conducted at 10 worksites in the northeastern United States . Worksites were paired and allocated into intervention and control conditions . Within- and between-groups changes in mean BMI s and in the percentage of overweight or obese employees were examined in a volunteer sample . RESULTS Within-group mean BMI s decreased by 0.54 kilograms per meter squared ( P = .02 ) and 0.12 kilograms per meter squared ( P = .73 ) at the intervention and control worksites , respectively , result ing in a difference in differences ( DID ) decrease of 0.42 kilograms per meter squared ( P = .33 ) . The within-group percentage of overweight or obese employees decreased by 3.7 % ( P = .07 ) at the intervention worksites and increased by 4.9 % ( P = .1 ) at the control worksites , result ing in a DID decline of 8.6 % ( P = .02 ) . CONCLUSIONS Our findings support a worksite population strategy that might eventually reduce the prevalence of overweight and obesity by minimizing environmental exposures to calorically dense foods and increasing exposures to opportunities for energy expenditure within worksite setting", "Background U.S. adults are at unprecedented risk of becoming overweight or obese , and most scientists believe the primary cause is an obesogenic environment . Worksites provide an opportunity to shape the environments of adults to reduce obesity risk . The goal of this group-r and omized trial was to implement a four-component environmental intervention at the worksite level to positively influence weight gain among employees over a two-year period . Environmental components focused on food availability and price , physical activity promotion , scale access , and media enhancements . Methods Six worksites in a U.S. metropolitan area were recruited and r and omized in pairs at the worksite level to either a two-year intervention or a no-contact control . Evaluations at baseline and two years included : 1 ) measured height and weight ; 2 ) online surveys of individual dietary intake and physical activity behaviors ; and 3 ) detailed worksite environment assessment . Results Mean participant age was 42.9 years ( range 18 - 75 ) , 62.6 % were women , 68.5 % were married or cohabiting , 88.6 % were white , 2.1 % Hispanic . Mean baseline BMI was 28.5 kg/m2 ( range 16.9 - 61.2 kg/m2 ) . A majority of intervention components were successfully implemented . However , there were no differences between sites in the key outcome of weight change over the two-year study period ( p = .36 ) . Conclusions Body mass was not significantly affected by environmental changes implemented for the trial . Results raise questions about whether environmental change at worksites is sufficient for population weight gain prevention . Trial Registration Clinical Trials.gov :", "OBJECTIVE To describe effects of 2 worksite health promotion programs for firefighters , both immediate outcomes and the long-term consequences for 4 years following the interventions . METHODS At baseline , 599 firefighters were assessed , r and omized by fire station to control and 2 different intervention conditions , and reevaluated with 6 annual follow-up measurements . RESULTS Both a team-centered peer-taught curriculum and an individual motivational interviewing intervention demonstrated positive effects on BMI , with team effects on nutrition behavior and physical activity at one year . Most differences between intervention and control groups dissipated at later annual assessment s. However , the trajectory of behaviors across time generally was positive for all groups , consistent with lasting effects and diffusion of program benefits across experimental groups within the worksites . CONCLUSIONS Although one-year programmatic effects did not remain over time , the long-term pattern of behaviors suggested these worksites as a whole were healthier more than 3 years following the interventions", "OBJECTIVE To describe the effectiveness , reach and implementation of a weight gain prevention intervention among public school employees . METHOD A multi-level intervention was tested in a cluster r and omized trial among 782 employees in 12 central Massachusetts public high schools from 2009 to 2012 . The intervention targeted the nutrition and physical activity environment and policies , the social environment and individual knowledge , attitudes and skills . The intervention was compared to a material s only condition . The primary outcome measures were change in weight and body mass index ( BMI ) at 24-month follow-up . Implementation of physical environment , policy and social environment strategies at the school and interpersonal levels , and intervention participation at the individual level were assessed . RESULTS At 24-month follow-up , there was a net change ( difference of the difference ) of -3.03 pounds ( p=.04 ) and of -.48 BMI units ( p=.05 ) between intervention and comparison conditions . The majority of intervention strategies were successfully implemented by all intervention schools , although establishing formal policies was challenging . Employee participation in programs targeting the physical and social environment was maintained over time . CONCLUSION This study supports that a multi-level intervention integrated within the organizational culture can be successfully implemented and prevent weight gain in public high school employees", "Background Insufficient PA has been shown to cluster with other CVD risk factors including insufficient fruit and vegetable intake , overweight , increased serum cholesterol concentrations and elevated blood pressure . This paper describes the development of Working on Wellness ( WOW ) , a worksite intervention program incorporating motivational interviewing by wellness specialists , targeting employees at risk . In addition , we describe the evaluation the effectiveness of the intervention among employees at increased risk for cardiovascular disease . Methods The intervention mapping ( IM ) protocol was used in the planning and design of WOW . Focus group discussion s and interviews with employees and managers identified the importance of addressing risk factors for CVD at the worksite . Based on the employees ’ preference for individual counselling , and previous evidence of the effectiveness of this approach in the worksite setting , we decided to use motivational interviewing as part of the intervention strategy . Thus , as a cluster-r and omised , controlled control trial , employees at increased risk for CVD ( N = 928 ) will be assigned to a control or an intervention group , based on company r and om allocation . The sessions will include motivational interviewing techniques , comprised of two face-to-face and four telephonic sessions , with the primary aim to increase habitual levels of PA . Measures will take place at baseline , 6 and 12 months . Secondary outcomes include changes in nutritional habits , serum cholesterol and glucose concentrations , blood pressure and BMI . In addition , healthcare expenditure and absenteeism will be measured for the economic evaluation . Analysis of variance will be performed to determine whether there were significant changes in physical activity habits in the intervention and control groups at 6 and 12 months . Discussion The formative work on which this intervention is based suggests that the strategy of targeting employees at increased risk for CVD is preferred . Importantly , this study extends the work of a previous , similar study , Health Under Construction , in a different setting . Finally , this study will allow an economic evaluation of the intervention that will be an important outcome for health care funders , who ultimately will be responsible for implementation of such an intervention . Trial registration United States Clinical Trails Register NCT", "Objective To determine the effectiveness of an individually-targeted Internet-based intervention with monetary incentives ( INCENT ) at reducing weight of overweight and obese employees when compared to a less-intensive intervention ( Livin ’ My Weigh [ LMW ] ) 6-months after program initiation . Design and Methods Twenty-eight worksites were r and omly assigned to either INCENT or LMW conditions . Both programs used evidence -based strategies to support weight loss . INCENT was delivered via daily e-mails over 12 months while LMW was delivered quarterly via both newsletters and onsite educational sessions . Generalized linear mixed models were conducted for weight change from baseline to 6-month post program and using an intention-to-treat ( ITT ) analysis to include all participants with baseline weight measurements . Results Across 28 worksites , 1,790 employees ( M=47 years of age ; 79 % Caucasian ; 74 % women ) participated . Participants lost an average of 2.27 lbs ( p BMI decrease of 0.36 kg/m2 ( p BMI decrease of 0.20 kg/m2 ( p INCENT and LMW group in weight loss and BMI reduction were not statistically significant . Conclusion The current study suggests that INCENT and a minimal intervention alternative may be effective approaches to help decrease the overall obesity burden within worksites", "Background Weight management constitutes a substantial problem particularly among groups of low socio-economic status . Interventions at work places may be a solution , but high quality worksite interventions documenting prolonged weight loss are lacking . This paper presents results of an intervention aim ed to achieve a 12 months weight loss among overweight health care workers . Methods Ninety-eight overweight female health care workers were r and omized into an intervention or a reference group . The intervention consisted of diet , physical exercise and cognitive behavioral training during working hours 1 hour/week . The reference group was offered monthly oral presentations . Several anthropometric measures , blood pressure , cardiorespiratory fitness , maximal muscle strength , and musculoskeletal pain were measured before and after the 12-months intervention period . Data were analyzed by intention-to-treat analysis . Results The intervention group significantly reduced body weight by 6 kg ( p BMI by 2.2 ( p body fat percentage by 2.8 ( p body weight , BMI and body fat percentage among overweight female health care workers over 12 months . The positive results support the workplace as an efficient arena for weight loss among overweight females . Trial registration NCT01015716", "OBJECTIVES To improve nutrition and physical activity of county employees and promote weight loss . DESIGN R and om assignment to begin the program when first offered or after 3 months ( \" wait control \" group ) . SETTING Worksite . PARTICIPANTS Onondaga County employees ( n = 45 ) at risk for diabetes ( n = 35 ) or with diabetes ( n = 10 ) . Mean ( ±SD ) age = 51.2 ( ± 8.0 ) years and body mass index ( BMI ) = 37.3 ± ( 6.8 kg/m ) . INTERVENTION Twelve weekly healthy lifestyle sessions based on the Diabetes Prevention Program curriculum , followed by monthly sessions for up to 12 months . OUTCOMES Medical : Weight , BMI , waist circumference , blood pressure , fasting glucose , lipid , and hemoglobin A1c levels . Psychosocial/behavioral : Health-related quality of life Short Form-12 , Impact of Weight on Quality of Life Scale ) , physical activity ( International Physical Activity Question naire ) , eating behavior ( 3-Factor Eating Question naire , National Cancer Institute Fat Screener ) , job satisfaction . RESULTS The intervention group lost significant weight compared to the wait control group over the first 3 months ( mean [ 95 % CI ] , -2.23 kg [ -3.5 to 0.97 ] ) vs [ + 0.73 kg ( + 0.17 to + 1.28 ) ] , with a decrease in BMI ( P and waist circumference ( P = .004 ) , an increase in physical activity ( International Physical Activity Question naire , P = .011 ) and lower dietary fat intake ( P = .018 ) . Over 12 months , 22.5 % ( 9/40 ) lost more than 5 % body weight and 12.5 % ( 5/40 ) lost more than 7 % body weight . After the first 3 months , there was gradual partial weight regain but reduction in waist circumference was maintained . The intervention group demonstrated significant improvement in Impact of Weight on Quality of Life Scale ( P , 3-Factor Eating ( cognitive restraint P .003 , and emotional eating P = .001 ) , International Physical Activity Question naire ( P = .011 ) , and Short Form-12 Physical Component Summary ( P = .048 ) . No improvements were observed in blood pressure , lipid , hemoglobin A1c , or glucose levels . Job satisfaction was inversely related to BMI at baseline ( P = .001 ) with a trend for improvement with the modest weight loss . CONCLUSIONS A worksite intervention program can help government employees adopt healthier lifestyles and achieve modest weight loss", "Objective : To examine whether obesity is associated with increased presenteeism ( health-related limitations at work ) . Methods : R and omly selected manufacturing employees ( n = 341 ) were assessed via height and weight measures , demographic survey , wage data , and the Work Limitations Question naire . The Work Limitations Question naire measures productivity on four dimensions . Analyses of variance and analyses of covariance were computed to identify productivity differences based on body mass index ( BMI ) . Results : Moderately or extremely obese workers ( BMI ≥35 ) experienced the greatest health-related work limitations , specifically regarding time needed to complete tasks and ability to perform physical job dem and s. These workers experienced a 4.2 % health-related loss in productivity , 1.18 % more than all other employees , which equates to an additional $ 506 annually in lost productivity per worker . Conclusions : The relationship between BMI and presenteeism is characterized by a threshold effect , where extremely or moderately obese workers are significantly less productive than mildly obese workers", "Background We investigated the risk of chronic liver disease ( CLD ) due to alcohol consumption and body mass index ( BMI ) and the effects of their interaction in a prospect i ve cohort study of women recruited to the UKCTOCS trial . Methods 95,126 post-menopausal women without documented CLD were stratified into 12 groups defined by combinations of BMI ( normal , overweight , obese ) and alcohol consumption ( none , , and followed for an average of 5.1 years . Hazard ratios ( HR ) were calculated for incident liver-related events ( LRE ) . Results First LREs were reported in 325 ( 0.34 % ) participants . Compared to women with normal BMI , HR = 1.44 ( 95 % CI ; 1.10–1.87 ) in the overweight group and HR = 2.25 ( 95 % CI ; 1.70–2.97 ) in the obese group , adjusted for alcohol and potential confounders . Compared to those abstinent from alcohol , HR = 0.70 ( 95 % CI ; 0.55–0.88 ) for alcohol , HR for LRE in obese women consuming ≥21 units/week was 2.86 ( 95 % CI ; 0.67–12.42 ) , 1.58 ( 95 % CI ; 0.96–2.61 ) for obese women drinking no significant interaction between BMI and alcohol . Conclusion High BMI and alcohol consumption and abstinence are risk factors for CLD in post-menopausal women . However , BMI and alcohol do not demonstrate significant interaction in this group . Trial registration UKCTOCS is registered as an International St and ard R and omised Controlled Trial , number IS RCT N22488978 . Registered 06/04/2000", "BACKGROUND The long-term effectiveness of multicomponent worksite health promotion programs targeting cardiovascular disease risk factors remains unclear in Japan . This study was conducted to evaluate the effectiveness of such a health promotion program consisting of a main program provided over 4 days and a follow-up program provided over 1 year . METHODS The subjects of this r and omized controlled trial were male employees working for a building maintenance company in Japan . The intervention group ( n = 152 ) and the control group ( n = 150 ) consisted of employees having abnormal findings in at least one of the following items at baseline health examination : body mass index ( BMI ) , systolic ( SBP ) or diastolic blood pressure , total cholesterol , HDL cholesterol , triglycerides , and fasting blood glucose . Evaluation was conducted at 18 months after the main program . RESULTS BMI , SBP , total cholesterol , and triglycerides improved significantly in the intervention group compared with the control group ( P BMI , total cholesterol , and triglycerides improved significantly in the intervention group ( P multicomponent health promotion program provided to employees was shown to be effective in improving obesity , high blood pressure , and hyperlipidemia when evaluated 18 months after the main intervention program", "Objective To evaluate 8-year weight losses achieved with intensive lifestyle intervention ( ILI ) in the Look AHEAD ( Action for Health in Diabetes ) study . Design and Methods Look AHEAD assessed the effects of intentional weight loss on cardiovascular morbidity and mortality in 5,145 overweight/obese adults with type 2 diabetes , r and omly assigned to ILI or usual care ( i.e. , diabetes support and education [ DSE ] ) . The ILI provided comprehensive behavioral weight loss counseling over 8 years ; DSE participants received periodic group education only . Results All participants had the opportunity to complete 8 years of intervention before Look AHEAD was halted in September 2012 ; ≥88 % of both groups completed the 8-year outcomes assessment . ILI and DSE participants lost ( mean±SE ) 4.7±0.2 % and 2.1±0.2 % of initial weight , respectively ( p ≥10 % ( p ILI participants , compared with DSE , reported greater practice of several key weight-control behaviors . These behaviors also distinguished ILI participants who lost ≥10 % and kept it off from those who lost but regained . Conclusions Look AHEAD ’s ILI produced clinical ly meaningful weight loss ( ≥5 % ) at year 8 in 50 % of patients with type 2 diabetes and can be used to manage other obesity-related co-morbid conditions . Trial Registration clinical trials.gov Identifier :", "BACKGROUND This study assessed the effects of the Health Works for Women ( HWW ) intervention on improving multiple behaviors including nutrition and physical activity among rural female blue-collar employees in North Carolina . METHODS Nine small to mid-size workplaces were r and omly assigned to either intervention or delayed intervention conditions . After a baseline survey , an intervention consisting of two computer-tailored magazines and a natural helpers program was conducted over 18 months . Delayed worksites received one tailored magazine . Approximately 77 and 76 % of baseline respondents completed follow-up surveys at 6 and 18 months , respectively , and 538 women ( 63 % ) completed all three surveys . RESULTS At the 18-month follow-up , the intervention group had increased fruit and vegetable consumption by 0.7 daily servings compared to no change in the delayed group ( P fat intake were observed at 6 months ( P strengthening and flexibility exercise compared to the delayed group . The rates of smoking cessation and cancer screening did not differ between study groups . CONCLUSIONS The HWW project was a successful model for achieving certain health behavior changes among blue-collar women", "CONTEXT Behavioral weight loss interventions achieve short-term success , but re-gain is common . OBJECTIVE To compare 2 weight loss maintenance interventions with a self-directed control group . DESIGN , SETTING , AND PARTICIPANTS Two-phase trial in which 1032 overweight or obese adults ( 38 % African American , 63 % women ) with hypertension , dyslipidemia , or both who had lost at least 4 kg during a 6-month weight loss program ( phase 1 ) were r and omized to a weight-loss maintenance intervention ( phase 2 ) . Enrollment at 4 academic centers occurred August 2003-July 2004 and r and omization , February-December 2004 . Data collection was completed in June 2007 . INTERVENTIONS After the phase 1 weight-loss program , participants were r and omized to one of the following groups for 30 months : monthly personal contact , unlimited access to an interactive technology-based intervention , or self-directed control . Main Outcome Changes in weight from r and omization . RESULTS Mean entry weight was 96.7 kg . During the initial 6-month program , mean weight loss was 8.5 kg . After r and omization , weight regain occurred . Participants in the personal-contact group regained less weight ( 4.0 kg ) than those in the self-directed group ( 5.5 kg ; mean difference at 30 months , -1.5 kg ; 95 % confidence interval [ CI ] , -2.4 to -0.6 kg ; P = .001 ) . At 30 months , weight regain did not differ between the interactive technology-based ( 5.2 kg ) and self-directed groups ( 5.5 kg ; mean difference -0.3 kg ; 95 % CI , -1.2 to 0.6 kg ; P = .51 ) ; however , weight regain was lower in the interactive technology-based than in the self-directed group at 18 months ( mean difference , -1.1 kg ; 95 % CI , -1.9 to -0.4 kg ; P = .003 ) and at 24 months ( mean difference , -0.9 kg ; 95 % CI , -1.7 to -0.02 kg ; P = .04 ) . At 30 months , the difference between the personal-contact and interactive technology-based group was -1.2 kg ( 95 % CI -2.1 to -0.3 ; P = .008 ) . Effects did not differ significantly by sex , race , age , and body mass index subgroups . Overall , 71 % of study participants remained below entry weight . CONCLUSIONS The majority of individuals who successfully completed an initial behavioral weight loss program maintained a weight below their initial level . Monthly brief personal contact provided modest benefit in sustaining weight loss , whereas an interactive technology-based intervention provided early but transient benefit . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00054925", "OBJECTIVE The results of an 18-month worksite intervention to prevent obesity among metropolitan transit workers are reported . METHODS Four garages in a major metropolitan area were r and omized to intervention or control groups . Data were collected during the fall of 2005 prior to the start of the intervention and during the fall of 2007 , after the intervention ended . Intervention program components at the garage included enhancement of the physical activity facilities , increased availability of and lower prices on healthy vending machine choices , and group behavioral programs . Mixed model estimates from cross-sectional and cohort sample s were pooled with weights inverse to the variance of their respective estimates of the intervention effects . RESULTS Measurement participation rates were 78 % at baseline and 74 % at follow-up . The intervention effect on garage mean BMI change was not significant ( -0.14 kg/m(2 ) ) . Energy intake decreased significantly , and fruit and vegetable intake increased significantly in intervention garages compared to control garages . Physical activity change was not significant . CONCLUSION Worksite environmental interventions for nutrition and physical activity behavior change may have limited impact on BMI among transit workers who spend most of their workday outside the worksite", "Objective . Weight assessment is a critical aid in patient care . It is particularly important in monitoring progression of pregnancies , heart failure status , and when adjusting medications . Although weight is generally determined using a scale , few studies have evaluated the precision of non-household scales . The objective of this study was to assess scale precision across a variety of setting s. Methods . An evaluation of scales from r and omly selected primary care clinics ( n=30 ) , diabetology/endocrinology clinics ( n=7 ) , weight loss facilities ( n=25 ) , and fitness centers ( n=30 ) was performed . Assessment s were completed on a total of 223 scales : 94 from primary care clinics , 32 from diabetology/endocrinology clinics , 39 from weight loss centers , and 58 from fitness centers . Scales were assessed for condition , location in facility , resting surface , commercial design ation , and calibration history . Scale precision was vali date d using 100 lb . ( 45.5 kg ) , 150 lb . ( 68.3 kg ) , 200 lb . ( 90.9 kg ) , and 250 lb . ( 113.6 kg ) certified weights . Results . Overall , scales demonstrated decreased precision with increased weight . At higher weights , more than 15 % of scales were off by more than 6 lbs . ( 2.3 kg ) , approximately 1 Body Mass Index ( BMI ) unit . While facility type was not significant , condition , location in facility , resting surface , commercial design ation , and calibration history were significant . Conclusions . This study demonstrates that many scales used to measure body weight are imprecise and that scales in health care setting s are no more precise than those in other facilities . Clinical decisions based on scales that are imprecise have the potential to cause iatrogenic complications in patient care", "Health information tailored to meet individuals ' unique needs has been shown to be more effective than generic information in promoting risk-reducing behavior changes . To explore mechanisms underlying tailoring 's effectiveness , this study r and omly assigned 198 overweight adults to receive weight-loss material s that were ( a ) tailored to the individual , ( b ) in an American Heart Association ( AHA ) brochure , or ( c ) AHA-content formatted to look like tailored material s. Participants who received tailored material s had more positive thoughts about the material s , positive personal connections to the material s , positive self- assessment thoughts , and positive thoughts indicating behavioral intention than those who received either of the untailored material s. The tailoring of health information can significantly improve the chances the information will be thoughtfully considered and can stimulate prebehavioral changes such as self- assessment and intention", "Objectives This study aims to evaluate the effectiveness of a \" blended \" workplace health-promotion intervention , alongside identification of key components beneficial for future implementation strategies . Methods Within a cluster r and omized controlled trial , 491 employees at increased risk of cardiovascular disease were allocated to the limited ( N=217 ; 9 clusters ) or extensive ( N=274 ; 8 clusters ) intervention . The extensive intervention consisted of motivational interviewing ( MI ) within the framework of a web-based health risk assessment ( HRA ) , a blended care approach . The limited intervention received solely the web-based HRA . Occupational health physicians ( N=21 ) within three organizations delivered the intervention . Implementation components investigated included : HRA ( reach and participation ) , newsletters ( percentage read ) , and MI sessions ( number and quality ) . MI quality was determined by scoring audiotaped MI sessions , using the MI treatment integrity code . After 6 and 12 months , effects on participation in health-promotion activities and its associations with components of implementation were determined by mixed-effects models . Results Over 80 % of employees participated in health-promotion activities , with an additional 8 % in the extensive compared to the limited group . In the extensive intervention , those with more or better quality MI sessions were more likely to participate in health-promotion activities . Increased MI quality was associated with sustained participation . Conclusions This study suggests that participation in health-promotion activities can be increased by adding MI to a web-based approach and improving the quality of the MI delivered . Interventions with MI should include optimized delivery and quality of MI sessions", "BACKGROUND Obesity causes frailty in older adults ; however , weight loss might accelerate age‐related loss of muscle and bone mass and result ant sarcopenia and osteopenia . METHODS In this clinical trial involving 160 obese older adults , we evaluated the effectiveness of several exercise modes in reversing frailty and preventing reduction in muscle and bone mass induced by weight loss . Participants were r and omly assigned to a weight‐management program plus one of three exercise programs — aerobic training , resistance training , or combined aerobic and resistance training — or to a control group ( no weight‐management or exercise program ) . The primary outcome was the change in Physical Performance Test score from baseline to 6 months ( scores range from 0 to 36 points ; higher scores indicate better performance ) . Secondary outcomes included changes in other frailty measures , body composition , bone mineral density , and physical functions . RESULTS A total of 141 participants completed the study . The Physical Performance Test score increased more in the combination group than in the aerobic and resistance groups ( 27.9 to 33.4 points [ 21 % increase ] vs. 29.3 to 33.2 points [ 14 % increase ] and 28.8 to 32.7 points [ 14 % increase ] , respectively ; P=0.01 and P=0.02 after Bonferroni correction ) ; the scores increased more in all exercise groups than in the control group ( P comparisons ) . Peak oxygen consumption ( milliliters per kilogram of body weight per minute ) increased more in the combination and aerobic groups ( 17.2 to 20.3 [ 17 % increase ] and 17.6 to 20.9 [ 18 % increase ] , respectively ) than in the resistance group ( 17.0 to 18.3 [ 8 % increase ] ) ( P comparisons ) . Strength increased more in the combination and resistance groups ( 272 to 320 kg [ 18 % increase ] and 288 to 337 kg [ 19 % increase ] , respectively ) than in the aerobic group ( 265 to 270 kg [ 4 % increase ] ) ( P both comparisons ) . Body weight decreased by 9 % in all exercise groups but did not change significantly in the control group . Lean mass decreased less in the combination and resistance groups than in the aerobic group ( 56.5 to 54.8 kg [ 3 % decrease ] and 58.1 to 57.1 kg [ 2 % decrease ] , respectively , vs. 55.0 to 52.3 kg [ 5 % decrease ] ) , as did bone mineral density at the total hip ( grams per square centimeter ; 1.010 to 0.996 [ 1 % decrease ] and 1.047 to 1.041 [ 0.5 % decrease ] , respectively , vs. 1.018 to 0.991 [ 3 % decrease ] ) ( P comparisons ) . Exercise‐related adverse events included musculoskeletal injuries . CONCLUSIONS Of the methods tested , weight loss plus combined aerobic and resistance exercise was the most effective in improving functional status of obese older adults . ( Funded by the National Institutes of Health ; LITOE Clinical Trials.gov number , NCT01065636 .", "This study evaluated health benefits of long-term participation in an employer-based wellness program , focusing on selected chronic disease risk factors . A repeated measures longitudinal time-series study was conducted of 8 years of existing prospect ively collected annual data , including clinical measures of weight , blood pressure , cholesterol , and body fat percent . Participants were divided into their risk levels at baseline . Outcomes were compared to level of participation , for which annual points earned was a surrogate . Participants had lower increases in body mass index ( BMI ) than the general population had during the same time period . Greatest improvements in BMI , blood pressure , and cholesterol were seen in those at highest risk levels at baseline and in those whose physical activity increased over time . It was found that long-term participation in this program improved BMI , blood pressure , and cholesterol . Most benefits were found for those in high-risk groups . This program should recruit more employees in high health risk categories and emphasize retention and increased levels of participation" ]	411896ea-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Although there are controversial issues ( the " American view " and the " European view " ) regarding the construct and definition of agoraphobia ( AG ) , this syndrome is well recognized and it is a burden in the lives of millions of people worldwide . To better clarify the role of drug therapy in AG , the authors summarized and discussed recent evidence on pharmacological treatments , based on clinical trials available from 2000 , with the aim of highlighting pharmacotherapies that may improve this complex syndrome . METHODS A systematic review of the literature regarding the pharmacological treatment of AG was carried out using MEDLINE , EBSCO , and Cochrane data bases , with keywords individuated by MeSH research . Only r and omized , placebo-controlled studies or comparative clinical trials were included . RESULTS After selection , 25 studies were included . All the selected studies included patients with AG associated with panic disorder . Effective compounds included selective serotonin reuptake inhibitors , serotonin-norepinephrine reuptake inhibitors , tricyclic antidepressants , selective noradrenergic reuptake inhibitors , and benzodiazepines . Paroxetine , sertraline , citalopram , escitalopram , and clomipramine showed the most consistent results , while fluvoxamine , fluoxetine , and imipramine showed limited efficacy . Preliminary results suggested the potential efficacy of inositol ; D-cycloserine showed mixed results for its ability to improve the outcome of exposure-based cognitive behavioral therapy . More studies with the latter compounds are needed before drawing definitive conclusions . CONCLUSION No studies have been specifically oriented toward evaluating the effect of drugs on AG ; in the available studies , the improvement of AG might have been the consequence of the reduction of panic attacks . Before developing a " true " psychopharmacology of AG it is crucial to clarify its definition . There may be several potential mechanisms involved , including fear-learning processes , balance system dysfunction , high light sensitivity , and impaired visuospatial abilities , but further studies are warranted	[ "Few r and omized controlled trials have included panic disorder patients with moderate to severe agoraphobia . Therefore , this population was studied using pharmacotherapy as well as psychotherapy . At the time of the study , imipramine was widely used as a pharmacological treatment . Also , current practice guidelines for patients with panic disorder find selective serotonin reuptake inhibitors and tricyclic antidepressants roughly comparable in terms of efficacy . Therefore , the main objective of this study is to compare four psychosocial treatments — cognitive and grade d in vivo exposure treatments , grade d in vivo exposure , cognitive treatment , and supportive therapy — to evaluate the benefits of combining cognitive therapy with exposure in vivo . These treatments were combined with imipramine or placebo for a total of eight experimental conditions . Participants presented moderate to severe agoraphobia . The method involved a r and omized , double‐blind , placebo‐controlled trial with 137 participants who completed a 14‐session protocol involving the treatments just mentioned . Measures were taken at baseline and posttreatment and at 3‐ , 6‐ , and 12‐month follow‐up . All treatment conditions were statistically and clinical ly effective in reducing self‐reported panic – agoraphobia symptoms over the 1‐year follow‐up . No statistical differences were observed between imipramine and placebo conditions . This study found that all treatment modalities helped reduce panic and agoraphobic symptomatology over a 1‐year follow‐up period . These surprising results support the need to document the relations among the various components of an intervention . This would make it possible to assess the relative efficacy of the treatment components rather than of the intervention as a whole", "BACKGROUND Traditional pharmacological approaches to treating psychiatric disorders focus on correcting presumed biochemical abnormalities . However , some disorders , particularly the anxiety-related disorders exemplified by specific phobia , have an emotional learning component to them that can be facilitated with psychotherapy . OBJECTIVE To determine whether D-cycloserine ( DCS ) , a partial agonist at the N-methyl-d-aspartate receptor that has previously been shown to improve extinction of fear in rodents , will also improve extinction of fear in human phobic patients undergoing behavioral exposure therapy . DESIGN R and omized , double-blind , placebo-controlled trial examining DCS vs placebo treatment in combination with a precisely controlled exposure paradigm . SETTING Participants were recruited from the general community to a research clinic . PARTICIPANTS Twenty-eight subjects with acrophobia diagnosed by the Structured Clinical Interview for DSM-IV were enrolled . INTERVENTIONS After we obtained pretreatment measures of fear , subjects were treated with 2 sessions of behavioral exposure therapy using virtual reality exposure to heights within a virtual glass elevator . Single doses of placebo or DCS were taken prior to each of the 2 sessions of virtual reality exposure therapy . Subjects , therapists , and assessors were blind to the treatment condition . Subjects returned at 1 week and 3 months posttreatment for measures to determine the presence and severity of acrophobia symptoms . MAIN OUTCOME MEASURES Included were measures of acrophobia within the virtual environment , measures of acrophobia in the real world , and general measures of overall improvement . An objective measure of fear , electrodermal skin fluctuation , was also included during the virtual exposure to heights . Symptoms were assessed by self-report and by independent assessors at approximately 1 week and 3 months posttreatment . RESULTS Exposure therapy combined with DCS result ed in significantly larger reductions of acrophobia symptoms on all main outcome measures . Subjects receiving DCS had significantly more improvement compared with subjects receiving placebo within the virtual environment ( 1 week after treatment , P posttreatment skin conductance fluctuations during the virtual exposure ( P placebo on general measures of real-world acrophobia symptoms ( acrophobia avoidance [ P acrophobia anxiety [ P attitudes toward heights [ P clinical global improvement [ P number of self-exposures to real-world heights [ P ] ) ; the improvement was evident early in treatment and was maintained at 3 months . CONCLUSION These pilot data provide initial support for the use of acute dosing of DCS as an adjunct to exposure-based psychotherapy to accelerate the associative learning processes that contribute to correcting psychopathology", "In spite of excessive fear during a panic attack , studies have found no or little evidence for an activation of cortisol during natural panic attacks . Whether this phenomenon is related to psychopathology or outcome of psychotherapy is unknown . In this study , 10 patients with panic disorder and agoraphobia were treated with cognitive behavioural therapy including 3 in-vivo exposures ( flooding ) to individual phobic situations . Before , during and after exposure , the level of subjective fear was assessed and blood was collected simultaneously . Cortisol and ACTH were analysed from plasma . Ten matched healthy control subjects went through the same procedure . Fear and stress hormones during exposure were compared in patients and controls as well as related to therapy outcome at the end of therapy and 2 follow-ups in patients . Results showed that the concentrations of cortisol and ACTH did not significantly increase during exposure . Patients ' cortisol concentrations were higher than those of controls at baseline and during exposure , while ACTH concentrations were comparable before and during exposure , and even lower than those of controls at recovery . Cortisol concentrations were moderately but consistently correlated to therapy outcome , i.e. patients with least cortisol release during exposure profited least from therapy . The study showed that a lack of stimulation of the HPA system at repeated confrontation with the phobic situation was related to therapeutic outcome . Mechanisms of action via the influence of cortisol on extinction learning or the inhibition of central excitatory neurotransmission are conceivable", "BACKGROUND Escitalopram , the therapeutically active isomer of the racemic selective serotonin reuptake inhibitor antidepressant citalopram , has shown significant anxiolytic effects in placebo-controlled clinical trials of social anxiety disorder , generalized anxiety disorder , and anxiety symptoms associated with major depression . This study evaluated the safety and efficacy of escitalopram in out patients diagnosed with panic disorder . METHOD Male and female out patients between 18 and 80 years of age meeting DSM-IV criteria for panic disorder , with or without agoraphobia , were r and omly assigned to 10 weeks of double-blind treatment with escitalopram , citalopram , or placebo in a study conducted from September 1999 to July 2001 . The primary measure of efficacy was panic attack frequency at week 10 relative to baseline , as assessed by the Modified Sheehan Panic and Anticipatory Anxiety Scale . RESULTS A total of 366 subjects ( 128 escitalopram patients , 119 citalopram patients , and 119 placebo patients ) received at least 1 dose of double-blind treatment . The frequency of panic attacks was statistically significantly improved ( p = .04 ) , and the increase in percentage of patients with zero panic attacks reached borderline significance ( p = .051 ) , in the escitalopram-treated group relative to the placebo-treated group . Both escitalopram and citalopram statistically significantly reduced panic disorder symptoms and severity versus placebo at endpoint ( p Panic and Agoraphobia Scale total score , the Clinical Global Impressions scale , the Patient Global Evaluation , and the Quality of Life Enjoyment and Satisfaction Question naire . Treatment with escitalopram was safe and well tolerated , with a similar incidence of the most common adverse events for the escitalopram and placebo groups . The rate of discontinuation for adverse events was 6.3 % for escitalopram , 8.4 % for citalopram , and 7.6 % for placebo . CONCLUSION Escitalopram is efficacious , safe , and well tolerated in the treatment of panic disorder", "CONTEXT This study makes a comparison between two subtypes of panic disorder regarding the clinical efficacy of clonazepam , a benzodiazepine . OBJECTIVES To evaluate the clinical efficacy of clonazepam in a fixed dosage ( 2 mg/day ) , compared to placebo , in the treatment of panic disorder patients and to verify whether there are any differences in the responses to clonazepam between panic disorder patients with the respiratory and non-respiratory subtypes . TYPE OF STUDY R and omized study with clonazepam and placebo . SETTING Outpatient Anxiety and Depression Unit of the Institute of Psychiatry , Universidade Federal do Rio de Janeiro , Rio de Janeiro , Brazil . PARTICIPANTS 34 patients with a diagnosis of panic disorder with agoraphobia , between 18 and 55 years old . PROCEDURES Administration of clonazepam or placebo for 6 weeks , in panic disorder patients , after they were classified within two subtypes of panic disorder : respiratory and non-respiratory . MAIN MEASUREMENTS Changes in the number of panic attacks in comparison with the period before the beginning of the study ; Hamilton Anxiety Scale ; Global Clinical Impression Scale ; and Patient 's Global Impression scale . RESULTS In the group that received clonazepam , by the end of the 6th week there was a statistically significant clinical improvement , shown by the remission of panic attacks ( p anxiety ( p = 0.024 ) . In the group that received clonazepam there was no significant difference between the respiratory and non-respiratory subtypes of panic disorder , regarding the therapeutic response to clonazepam . CONCLUSION Clonazepam was equally effective in the treatment of the respiratory and non-respiratory subtypes of panic disorder , suggesting there is no difference in the therapeutic response between the two subtypes", "Agoraphobia in panic disorder ( PD ) has been related to abnormal balance system function . Vision influences balance and behavioural adaptations ; peripheral vision influences orienting and fast defensive reactions whereas central vision analyzes details of objects . We have hypothesized that the abnormal balance function in PD could be mainly related to peripheral vision as part of a defensive alarm system in the brain . In 25 patients with PD and agoraphobia and 31 healthy controls we assessed , by posturography , balance system reactivity to video-films projected in peripheral and central visual fields ( r and omized sequence ) . Length , velocity and surface of body sway were calculated . Patients increased their body sway during peripheral stimulation , whereas controls did not ; the two groups showed a similar increase of body sway during central stimulation . Anxiety levels during peripheral stimulation significantly influenced the postural response in the group of patients . These preliminary results suggest that the higher visual sensitivity to peripheral stimulation in patients with PD and agoraphobia may be linked to a more active \" visual alarm system \" involving visual , vestibular and limbic areas that might influence the development of agoraphobia in situations where environmental stimuli are uncertain", "BACKGROUND The results from our 1 year placebo-controlled maintenance/discontinuation study in remitted panic disorder with agoraphobia patients confirmed the significant prophylactic effectiveness of imipramine maintenance treatment but suggested that this may be necessary in only 37 % of the patients who relapse following discontinuation of 6 months acute imipramine treatment . This paper presents pilot data from a second year extension of the above-mentioned study with the aim of exploring the putative protective effects of maintenance imipramine therapy beyond the 1st year . METHOD Eighteen patients from the 30 who survived , in stable remission , the first 12 months of the maintenance/discontinuation study gave written consent to participate in a double-blind 2nd year extension phase with the knowledge that those on placebo will continue on the same condition ( N = 7 , PBO-PBO ) and those on imipramine ( N = 11 ) will be rer and omized to 2nd year maintenance ( N = 4 , IMI-IMI ) or placebo substitution ( N = 7 , IMI-PBO ) . The procedures continued unchanged from that of the 1st year of the study and patients were followed with planned assessment s every 2 months over the second 12-month experimental period of the study . RESULTS None of the IMI-IMI patients relapsed , two ( 28.5 % ) of the IMI-PBO patients relapsed , and two ( 28.5 % ) of PBO-PBO patients relapsed . The mean estimated time without relapse was 10 months and 9 months for IMI-PBO and PBO-PBO , respectively . The estimated probability of not relapsing was .64 for IMI-PBO and .60 for PBO-PBO ( Mantel-cox test chi2 = .84 , p = .77 ) . CONCLUSION These interlocking controlled observations tentatively suggest that a substantial degree of prophylactic efficacy continues and that a substantial need for continued prophylaxis exists beyond the 1st year of maintenance imipramine treatment in panic disorder with agoraphobia patients", "Experimental evidence suggests that panic disorder is characterized by abnormalities in the balance system function and that these abnormalities might be related to the severity of agoraphobic avoidance . Since the balance system can be modulated by the serotonergic system , we investigated the effect of a 6‐week treatment with citalopram on the balance system function in patients with panic disorder . Fifteen patients with panic disorder with/without agoraphobia underwent static posturography on days 0 and 42 . Static posturography and clinical assessment s were carried out by different investigators who were blind to each other . Static posturography showed high percentages of abnormal scores . Patients with no or low agoraphobic avoidance showed less abnormal posturographic measures than those with moderate to severe agoraphobia . After 6 weeks of treatment with citalopram there was a significant decrease of four out of six posturography measures in eyes‐closed and neck extension conditions , whereas no significant effect was found in the eyes‐open condition . This is the first report that suggests that the modulation of the serotonergic system can improve the balance system function in patients with panic disorder , particularly when visual information is lacking . In addition , our findings confirm the observation that many patients with panic disorder have abnormalities in their balance system function , supporting the idea that these abnormalities are mainly related to agoraphobic avoidance . Depression and Anxiety 17:101–106 , 2003 . © 2003 Wiley‐Liss ,", "A r and omized , double-blind , placebo-controlled , parallel-group study was conducted to evaluate the efficacy and safety of gabapentin in relieving the symptoms of panic disorder . One hundred three patients were r and omly assigned to receive double-blind treatment with either gabapentin ( dosed flexibly between 600 and 3,600 mg/day ) or placebo for 8 weeks . No overall drug/placebo difference was observed in scores on the Panic and Agoraphobia Scale ( PAS ) ( p = 0.606 ) . A post hoc analysis was used to evaluate the more severely ill patients as defined by the primary outcome measure ( PAS score > or = 20 ) . In this population , the gabapentin-treated patients showed significant improvement in the PAS change score ( p = 0.04 ) . In patients with a PAS score of 20 or greater , women showed a greater response than men regardless of treatment . Adverse events were consistent with the known side effect profile of gabapentin and included somnolence , headache , and dizziness . One patient experienced a serious adverse event during the study . No deaths were reported . The results of this study suggest that gabapentin may have anxiolytic effects in more severely ill patients with panic disorder", "INTRODUCTION Serotonergic agents have greater effectiveness than noradrenergic ones in the treatment of Panic Disorder ( PD ) . However preliminary studies suggested that reboxetine might be effective in the treatment of PD . We compared the effectiveness and tolerability of reboxetine and paroxetine in the treatment of PD . METHODS Sixty-eight patients with PD were assigned to treatment groups in a single-blind , r and omized design . Each patient was assessed at day 0 and 90 by the Panic Associated Symptoms Scale ( PASS ) , the Sheehan Disability Scale ( SDS ) and the Fear Question naire ( FQ ) . Side effects were also recorded . RESULTS Reduction of PASS scores was significantly greater in the paroxetine group than in the reboxetine one . Vice versa we did not find any significant differences for other outcome measures . Sexual dysfunction and weight gain were significantly less frequent in the reboxetine group . CONCLUSIONS The results showed a greater effect of paroxetine on panic attacks than reboxetine , while no differences for anticipatory anxiety and avoidance were found , suggesting a different role of noradrenaline and serotonin in the treatment of PD", "Behavioral exposure therapy of anxiety disorders is believed to rely on fear extinction . Because pre clinical studies have shown that glucocorticoids can promote extinction processes , we aim ed at investigating whether the administration of these hormones might be useful in enhancing exposure therapy . In a r and omized , double-blind , placebo-controlled study , 40 patients with specific phobia for heights were treated with three sessions of exposure therapy using virtual reality exposure to heights . Cortisol ( 20 mg ) or placebo was administered orally 1 h before each of the treatment sessions . Subjects returned for a posttreatment assessment 3–5 d after the last treatment session and for a follow-up assessment after 1 mo . Adding cortisol to exposure therapy result ed in a significantly greater reduction in fear of heights as measured with the acrophobia question naire ( AQ ) both at posttreatment and at follow-up , compared with placebo . Furthermore , subjects receiving cortisol showed a significantly greater reduction in acute anxiety during virtual exposure to a phobic situation at posttreatment and a significantly smaller exposure-induced increase in skin conductance level at follow-up . The present findings indicate that the administration of cortisol can enhance extinction-based psychotherapy", "Pagoclone is a cyclopyrrolone that is believed to act as a partial agonist at the γ-aminobutyric acid ( GABA ) A/benzodiazepine ( BDZ ) receptor . In theory , such partial agonists should be anxiolytic but lack the adverse side-effects of sedation , tolerance and withdrawal associated with full GABA-A/BDZ agonists . The objective of the r and omized double-blind crossover study was to assess whether pagoclone was an effective anti-panic agent and also to assess its side-effect profile . Patients recruited had a diagnosis of Panic Disorder ( DSM-IV ) with at least one panic attack per week . Following a 2-week screening period , patients entered a 6-week trial consisting of two 2-week treatment periods , each followed by a 1-week washout . Patients were r and omly assigned to receive either pagoclone 0.1 mg t.d.s . or placebo on their first treatment period and the converse on their second . The primary measure was daily panic attack dairy . Fourteen patients completed the study , the mean number of panic attacks during screening was 5.8 ± 0.8 ( SEM ) , this fell to 3.6 ± 0.5 during treatment with pagoclone ( p = 0.05 ) and 4.3 ± 0.8 with placebo ( p = 0.14 ) . There was no significant difference on direct comparison of pagoclone with placebo or in any of the secondary measures ( including Rickels withdrawal scale ) or the adverse event profiles . The study provides preliminary evidence that pagoclone has anxiolytic properties in the absence of typical BDZ side-effects . This is consistent with its theoretical mode of action as a partial agonist at the GABAA/BDZ receptor", "OBJECTIVE To assess the effectiveness of clonazepam , in a fixed dose ( 2 mg/day ) , compared with placebo in the treatment of panic disorder patients . METHOD 24 panic disorder patients with agoraphobia were r and omly selected . The diagnosis was obtained using the structured clinical interview for DSM-IV . All twenty-four subjects were r and omly assigned to either treatment with clonazepam ( 2 mg/day ) or placebo , during 6 weeks . Efficacy assessment s included : change from baseline in the number of panic attacks ; CGI scores for panic disorder ; Hamilton rating scale for anxiety ; and panic associated symptoms scale . RESULTS At the therapeutic endpoint , only one of 9 placebo patients ( 11.1 % ) were free of panic attacks , compared with 8 of 13 ( 61.5 % ) clonazepam patients ( Fisher exact test ; p=0,031 ) . CONCLUSION the results provide evidence for the efficacy of clonazepam in panic disorder patients", "OBJECTIVE Because they found in an earlier study that inositol , an important intracellular second-messenger precursor , was effective against depression in open and double-blind trials , the authors studied its effectiveness against panic disorder . METHOD Twenty-one patients with panic disorder with or without agoraphobia completed a double-blind , placebo-controlled , 4-week , r and om-assignment crossover treatment trial of 12 g/day of inositol . RESULTS The frequency and severity of panic attacks and the severity of agoraphobia declined significantly more after inositol than after placebo administration . Side effects were minimal . CONCLUSIONS The authors conclude that inositol 's efficacy , the absence of significant side effects , and the fact that inositol is a natural component of the human diet make it a potentially attractive therapeutic for panic disorder", "The purpose of this study was to test the following interrelated hypotheses in a larger sample by attempting to replicate supportive results from a small therapeutic study : ( 1 ) the pathogenesis of panic disorder includes at least two identifiable components : a biological component represented by spontaneous ( unexpected ) panic attacks , and a cognitive component represented by situational attacks and especially by phobias ; ( 2 ) these components respond differently to treatment ; ( 3 ) many biological processes respond to an effective intervention in proportion to their deviance from \" normal \" prior to treatment ( \" Law of Initial Value \" ) ; and ( 4 ) the response of spontaneous panic attacks to an effective treatment conforms to that model . Previously , the authors reanalyzed an 8-week therapeutic study of panic disorder that included groups treated with placebo and with imipramine ( 225 mg daily ) . The criteria of response were spontaneous panic attacks ( biological component ) , situational panic attacks ( both components ) , and agoraphobia ratings ( cognitive component ) . The analyses compared the regression lines for posttreatment status on pretreatment status in the imipramine and placebo groups . The effect of imipramine on spontaneous panic attacks fitted the hypothesized model : the pre-post slope in the placebo group was approximately 1 ( 45 degrees ) , whereas the slope in the imipramine group was approximately 0 . There was no significant difference in pre-post slopes between the imipramine and placebo groups for situational panic attacks or agoraphobia ratings . For this report , the authors applied the same approach to another larger data set from a study using a similar design , but a different antidepressant . In this multicenter , double-blind study , patients with panic disorder were r and omly assigned to receive 10 weeks of treatment with placebo ( N = 78 ) or fluoxetine 10 mg ( N = 84 ) or 20 mg ( N = 81 ) daily . Spontaneous and situational panic attacks were registered in a daily diary , and agoraphobia was rated at each visit . Using baseline and endpoint data , fluoxetine had a statistically significant , dose-dependent , suppressive effect on spontaneous panic attacks , as measured by the pre-post slopes in the three treatment groups . The placebo group showed some response ( slope = 0.69 ) . There were no significant drug effects on situational panic attacks . On ratings of agoraphobia , the slopes in the placebo and the fluoxetine 20 mg groups did not differ , but the slope in the fluoxetine 10 mg group was significantly less than that in the placebo group , suggesting a therapeutic drug effect on agoraphobia only at the lower dose . These results are consistent with the stated hypotheses . They suggest that the therapeutic effects of antidepressants on panic disorder may be due primarily to the specific suppression of spontaneous panic attacks among patients with high baseline pathologic findings . Implication s of these results for concepts of pathogenesis , clinical practice , and therapeutic research regarding panic disorder are discussed", "BACKGROUND It has been argued that measurement of outcome in panic disorder should not be limited to monitoring the number of panic attacks , but should include all domains that affect patient quality of life . METHODS Data from a r and omized prospect i ve comparison of escitalopram , citalopram , and placebo in patients with DSM-IV panic disorder were analyzed with regard to measurements of impairment of quality of life . The subscales of the Panic and Agoraphobia Scale ( P&A ) ( Panic Attacks , Agoraphobic Avoidance , Anticipatory Anxiety , Functional and Social Disability , and Worries about Health ) and the Quality of Life Enjoyment and Satisfaction Question naire ( Q-LES-Q ) were analyzed . RESULTS Treatment with escitalopram was associated with significant improvement on all 5 subscales of the P&A. Citalopram was significantly different from placebo in 3 subscales . Escitalopram and citalopram were significantly better than placebo in improving quality of life ( measured by the total score of the Q-LES-Q Scale ) . Escitalopram was superior to placebo on 12 of 16 items of the Q-LES-Q , while citalopram was superior on 7 items . CONCLUSION The P&A scale was more robust than measurement of panic frequency in differentiating medication from placebo . Escitalopram treatment was associated with improvement on all assessed domains that impair quality of life in panic disorder . Measurement of clinical improvement should not be solely based on panic attack frequency , but should also include assessment of a broad range of domains that affect patient quality of life", " D-cycloserine (DCS)-augmented exposure therapy has proven efficacy in the treatment of acrophobia , social phobia , panic disorder and OCD . Here we studied whether DCS can also improve the effect of cognitive behavioral therapy ( CBT ) in patients with agoraphobia and panic disorder . To this end , 39 patients with the diagnoses of agoraphobia and panic disorder were treated with 11 sessions of CBT including three individual in-vivo exposure sessions ( flooding ) , augmented with either 50 mg of DCS ( N=20 ) or placebo ( N=19 ) in a r and omized double blind design . Primary outcome was the total score of the panic and agoraphobia scale . Both groups profited considerably from therapy and DCS did not significantly improve this outcome ( p=0.475 ; η(2)p = 0.01 ) . However , there was a statistical trend ( p=0.075 ; η(2)p = 0.17 ) in the more severely ill patients that DCS accelerated symptom reduction in the primary outcome at post-therapy . No serious adverse effects occurred during the trial . We conclude that in patients with agoraphobia and panic disorder , DCS seems to lack an additional benefit to efficient cbt , probably due to a floor effect . Nonetheless , the acceleration of symptom reduction in severely ill patients might represent a valuable treatment option deserving further investigation", "It was proposed that pre-post regression slopes be used to index treatment response when the effect of baseline scores differed among treatments ( interaction between treatment and baseline score ) . Reanalyses of two studies using imipramine and fluoxetine in panic disorder showed doserelated decreases in pre-post slopes for the frequency of unexpected panic attacks , but not for the frequency of situational panic attacks or measures of agoraphobia . This report presents similar analyses of data from a study using moclobemide . Patients ( N = 452 ) with panic disorder were r and omized to placebo or a fixed dose of moclobemide ( 75 , 150 , 300 , 600 , or 900 mg/day ) . They were treated double-blindly and evaluated at baseline and 1 , 2 , 3 , 4 , 6 , and 8 weeks later . The authors analyzed the frequency of unexpected and situational panic attacks compiled from a daily diary , and fear and avoidance ratings based on the patient ’s main phobia using baseline ( pre ) and end-point ( post ) values for all r and omized patients . Adjoining dose groups were combined . Both unexpected and situational panic attacks showed systematic doserelated suppression of pre-post treatment slopes . Neither pre-post slopes nor adjusted posttreatment means for fear and avoidance differed reliably between treatment arms . This study replicates the authors ’ earlier findings , except for situational panic attacks , which probably were not reliably identified . Antidepressants selectively suppress panic attacks , especially unexpected attacks , but not agoraphobia . The findings are consistent with the hypothesis that panic disorder with agoraphobia has clinical ly separable biologic and cognitive components that respond differentially to treatment . Antidepressants benefit primarily patients with many unexpected panic attacks . Investigators should evaluate pre-post treatment slopes before comparing adjusted posttreatment means ( analysis of covariance )", "Only 70 % of patients respond to current treatments for panic disorder , and many discontinue drugs because of side effects . myo-Inositol , a natural isomer of glucose and a precursor for the second-messenger phosphatidyl-inositol system , has previously been found superior to placebo in the treatment of depression , panic disorder , and obsessive-compulsive disorder ( OCD ) , but a direct comparison with an established drug has never been performed . A double-blind , controlled , r and om-order crossover study was undertaken to compare the effect of inositol with that of fluvoxamine in panic disorder . Twenty patients completed 1 month of inositol up to 18 g/day and 1 month of fluvoxamine up to 150 mg/day . Improvements on Hamilton Rating Scale for Anxiety scores , agoraphobia scores , and Clinical Global Impressions Scale scores were similar for both treatments . In the first month , inositol reduced the number of panic attacks per week ( mean and SD ) by 4.0 ( 2 ) compared with a reduction of 2.4 ( 2 ) with fluvoxamine ( p = 0.049 ) . Nausea and tiredness were more common with fluvoxamine ( p = 0.02 and p = 0.01 , respectively ) . Because inositol is a natural compound with few known side effects , it is attractive to patients who are ambivalent about taking psychiatric medication . Continuing reports of inositol ’s efficacy in the treatment of depression , panic disorder , and OCD should stimulate replication studies", "Carbon dioxide ( CO2 ) inhalation induces acute anxiety and panic attacks in patients with Panic Disorder ( PD ) . Anti-panic drugs decrease CO2 reactivity after the first days of treatment ; however , the clinical meaning of this finding has not yet been established . This study investigated the effects of treatment with tricyclic antidepressants and selective serotonin re-uptake inhibitors ( SSRIs ) on CO2 reactivity and compared the relationships between 35 % CO2 hyperreactivity modulation and short-term clinical outcome . One hundred twenty-three patients with PD with or without agoraphobia who were hyperreactive to CO2 were r and omly assigned to treatment groups with imipramine , clomipramine , paroxetine , sertraline , or fluvoxamine . A double-blind , r and omized design was applied . Each patient received the 35 % CO2 challenge on days 0 , 7 , and 30 . The severity of clinical symptomatology was measured on days 0 and 30 . Decreased hyperreactivity to 35 % CO2 in all five treatment groups was already evident after the first week . The decrease in CO2 reactivity at the end of treatment was proportional to the degree of clinical improvement . Multiple regression analyses showed that the decrease in CO2 reactivity after the first week was a significant predictor for good clinical outcome after one month . The results of this study confirm evidence that psychoactive drugs effective in the treatment of PD decrease CO2 hyperreactivity . They also suggest that precocious modulation of CO2 reactivity might fairly reliably predict short-term clinical outcome in patients with “ respiratory ” PD", "BACKGROUND A new 13-item scale has been developed for measuring severity of illness in patients with panic disorder and agoraphobia , the Panic and Agoraphobia Scale ( P & A ) . The scale has five subscales covering the main factors that reduce quality of life in panic disorder patients ( panic attacks , avoidance , anticipatory anxiety , disability and worries about health ) . The application of this scale in a double-blind placebo-controlled panic disorder trial is described . At the same time , the aim of the study was to compare the therapeutic effects of aerobic exercise with a treatment of well-documented efficacy . METHODS Patients with Panic disorder ( DSM-IV ) were r and omly assigned to three treatment modalities : running ( n=45 ) , clomipramine ( n=15 ) or placebo ( n=15 ) . Treatment efficacy was measured with the Panic and Agoraphobia Scale ( P & A ) and other rating scales . RESULTS According to the P & A and other scales , both exercise and clomipramine led to a significant decrease of symptoms in comparison to placebo treatment . Clomipramine was significantly more effective and improved anxiety symptoms significantly earlier than exercise . The evaluation of the P & A subscales revealed that exercise exerted its effect mainly reducing anticipatory anxiew and panic-related disability . CONCLUSIONS The new Panic and Agoraphobia Scale was shown to be sensitive to differences between different panic treatments . Analysis of the scales five subscores may help to underst and mechanisms of action of panic disorder treatments", "To date , no large-scale , controlled trial comparing a serotonin-norepinephrine reuptake inhibitor and selective serotonin reuptake inhibitor with placebo for the treatment of panic disorder has been reported . This double-blind study compares the efficacy of venlafaxine extended-release ( ER ) and paroxetine with placebo . A total of 664 nondepressed adult out patients who met DSM-IV criteria for panic disorder ( with or without agoraphobia ) were r and omly assigned to 12 weeks of treatment with placebo or fixed-dose venlafaxine ER ( 75 mg/day or 150 mg/day ) , or paroxetine 40 mg/day . The primary measure was the percentage of patients free from full-symptom panic attacks , assessed with the Panic and Anticipatory Anxiety Scale ( PAAS ) . Secondary measures included the Panic Disorder Severity Scale , Clinical Global Impressions -- Severity ( CGI-S ) and --Improvement ( CGI-I ) scales ; response ( CGI-I rating of very much improved or much improved ) , remission ( CGI-S rating of not at all ill or borderline ill and no PAAS full-symptom panic attacks ) ; and measures of depression , anxiety , phobic fear and avoidance , anticipatory anxiety , functioning , and quality of life . Intent-to-treat , last observation carried forward analysis showed that mean improvement on most measures was greater with venlafaxine ER or paroxetine than with placebo . No significant differences were observed between active treatment groups . Panic-free rates at end point with active treatment ranged from 54 % to 61 % , compared with 35 % for placebo . Approximately 75 % of patients given active treatment were responders , and nearly 45 % achieved remission . The placebo response rate was slightly above 55 % , with remission near 25 % . Adverse events were mild or moderate and similar between active treatment groups . Venlafaxine ER and paroxetine were effective and well tolerated in the treatment of panic disorder", "OBJECTIVE This study evaluated time to response in the treatment of panic disorder with a selective serotonin reuptake inhibitor ( SSRI ) or serotonin norepinephrine reuptake inhibitor ( SNRI ) combined with alprazolam orally disintegrating tablets ( ODT ) , or SSRI/SNRI alone . DESIGN Subjects were r and omized to eight weeks open-label treatment with alprazolam ODT ( 4 weeks treatment followed by 3 - 4 week taper ) combined with an SSRI or SNRI , or treatment with SSRI/SNRI alone . SETTING The study was conducted under naturalistic conditions at 62 primary care and 34 psychiatric practice s. PARTICIPANTS Male or female subjects ≥18 years of age diagnosed with panic disorder , with or without agoraphobia . MEASUREMENTS The primary efficacy measure was time to response , defined as ≥50-percent decrease from baseline Hamilton Rating Scale for Anxiety ( HAM-A ) total score . Secondary measures included change from baseline in HAM-A scores and the Clinical Global Impression of Improvement ( CGI-I ) and Patient Global Impression ( PGI ) scales . RESULTS The intent-to-treat ( ITT ) population comprised 245 subjects . There was no statistical difference between treatment groups in time to response in the ITT population ; however , a prospect ively defined per protocol analysis revealed a statistically significant earlier onset of effect in subjects receiving SSRI/SNRI plus alprazolam ODT ( P ) . Mean change from baseline in HAM-A total score and clinician and patient measures of global improvement also showed statistically significant early advantages for combination therapy compared with SSRI/SNRI monotherapy . CONCLUSION Combined treatment of panic disorder with alprazolam ODT and an SSRI/SNRI may be associated with more rapid improvement in anxiety symptoms compared with an SSRI/SNRI alone", "OBJECTIVE To establish the long-term effectiveness of 3 treatments for DSM-IV panic disorder with or without agoraphobia : cognitive-behavioral therapy ( CBT ) , pharmacotherapy using a selective serotonin reuptake inhibitor ( SSRI ) , or the combination of both ( CBT + SSRI ) . As a secondary objective , the relationship between treatment outcome and 7 predictor variables was investigated . METHOD Patients were enrolled between April 2001 and September 2003 and were r and omly assigned to treatment . Academic and nonacademic clinical sites participated . Each treatment modality lasted 1 year . Pharmacotherapists were free to choose between 5 SSRIs currently marketed in The Netherl and s. Outcome was assessed after 9 months of treatment ( posttest 1 ) , after discontinuation of treatment ( posttest 2 ) , and 6 and 12 months after treatment discontinuation ( follow-up 1 and follow-up 2 ) . RESULTS In the sample ( N = 150 ) , 48 % did not suffer from agoraphobia or suffered from only mild agoraphobia , while 52 % suffered from moderate or severe agoraphobia . Patients in each treatment group improved significantly from pretest to posttest 1 on the primary outcome measures of level of anxiety ( P degree of coping ( P remitter status ( P depressive symptomatology ( P health-related quality of life ( P CBT + SSRI and SSRI as compared with CBT was observed at posttest 1 . However , at both follow-ups , differences between treatment modalities proved nonsignificant . Client satisfaction appeared to be high at treatment endpoint , while patients receiving CBT + SSRI appeared slightly ( P satisfied than those receiving CBT only . CONCLUSIONS No fall-off in gains was observed for either treatment modality after treatment discontinuation . SSRIs were associated with adverse events . Gains produced by CBT were slower to emerge than those produced by CBT + SSRI and SSRI , but CBT ended sooner . TRIAL REGISTRATION Netherl and s Trial Register ( www.trialregister.nl ) Identifier : IS RCT N8156869", "BACKGROUND Traditional combination strategies of cognitive-behavior therapy plus pharmacotherapy have met with disappointing results for anxiety disorders . Enhancement of cognitive-behavior therapy with d-cycloserine ( DCS ) pharmacotherapy represents a novel strategy for improving therapeutic learning from cognitive-behavior therapy that remains untested in panic disorder . METHOD This is a r and omized , double-blind , placebo-controlled augmentation trial examining the addition of isolated doses of 50 mg d-cycloserine or pill placebo to brief exposure-based cognitive-behavior therapy . R and omized participants were 31 out patients meeting DSM-IV criteria for panic disorder with or without agoraphobia , who were offered five sessions of manualized cognitive-behavior therapy emphasizing exposure to feared internal sensations ( interoceptive exposure ) but also including informational , cognitive , and situational exposure interventions . Doses of study drug were administered 1 hour before cognitive-behavior therapy sessions 3 to 5 . The primary outcome measures were the Panic Disorder Severity Scale ( PDSS ) and Clinicians ' Global Impressions of Severity . RESULTS Results indicated large effect sizes for the additive benefit of d-cycloserine augmentation of cognitive-behavior therapy for panic disorder . At posttreatment and 1 month follow-up , participants who received d-cycloserine versus placebo had better outcomes on the PDSS and global severity of disorder and were significantly more likely to have achieved clinical ly significant change status ( 77 % vs. 33 % ) . There were no significant adverse effects associated with DCS administration . CONCLUSIONS This pilot study extends support for the role of d-cycloserine in enhancing therapeutic learning from exposure-based cognitive-behavior therapy and is the first to do so in a protocol emphasizing exposure to feared internal sensations of anxiety in panic disorder", "It has been suggested that maintenance treatment of patients who have remitted panic disorder with agoraphobia beyond the six months of acute phase imipramine treatment may decrease the risk of relapse . This study further explores the relationship between relapse and duration of imipramine treatment in this population . Fifty-one patients , all in remission at the end of six months acute phase open trial with imipramine 2.25 mg/kg/day and r and omized to double-blind maintenance or placebo substitution , discontinued imipramine treatment eventually and were followed over a 12-month risk period : 27 during first year placebo substitution , 7 after 12 months of imipramine maintenance in placebo substitution , and 17 after variable duration s of imipramine maintenance in open discontinuation . There were no behaviorally oriented interventions or instructions at any time during the acute and maintenance phases of treatment or during imipramine discontinuation . Duration of imipramine treatment , the method of discontinuation ( open versus placebo substitution ) , or any of the 9 variables from the demographic , clinical , and open treatment domains that were entered in a Cox proportional hazard model did not predict relapse . The rate of relapse after only 6 months of treatment ( 10 out of 27 , 37 % ) was identical to the rate of relapse after 12 to 30 months of treatment ( 9 out of 24 , 37.5 % ) . The results suggest a lack of specific protective effects beyond prophylaxis and underscore the difficulty in predicting relapse in fully remitted panic disorder with agoraphobia patients . Early detection of relapse in patients who discontinue treatment may be a viable alternative to prediction", "Abstract Objectives . Regular aerobic exercise ( running ) has been shown to be superior to a pill placebo in the treatment of panic disorder . Combined drug and exercise treatment has not been investigated in r and omized controlled studies to date . Methods . This is a r and omized , 10-week , controlled , parallel group , pilot study . A total of 75 out patients with panic disorder with or without agoraphobia ( DSM-IV and ICD-10 ) received either ( 1 ) exercise plus paroxetine 40 mg/day ( n=21 ) , ( 2 ) relaxation plus paroxetine ( n=17 ) , ( 3 ) exercise plus pill placebo ( n=20 ) , or ( 4 ) relaxation plus pill placebo ( n=17 ) . Changes in the Panic and Agoraphobia Scale ( P&A ) , and the Clinical Global Impression Scale ( CGI ) underwent repeated measure analysis . Results . Effects sizes were large for all groups ( d=1.53–3.87 ) , however not significantly different . Paroxetine-treated patients were significantly more improved than placebo-treated patients . On the CGI , patients in the exercise groups ( plus paroxetine or placebo ) had a trend toward better improvement compared to relaxation ( P=0.06 ) . Response and remission rates were higher in the paroxetine compared to pill placebo groups . Conclusions . While paroxetine was superior to placebo , aerobic exercise did not differ from relaxation training in most efficacy measures", "Hendriks G‐J , Keijsers GPJ , Kampman M , Oude Voshaar RC , Verbraak MJPM , Broekman TG , Hoogduin CAL . A r and omized controlled study of paroxetine and cognitive‐behavioural therapy for late‐life panic disorder", "BACKGROUND Tricyclic antidepressants and selective serotonin reuptake inhibitors ( SSRIs ) as well as benzodiazepines have been shown to be effective for the treatment of panic disorder . The introduction of SSRIs has enabled a greater underst and ing of the role of serotonin in the etiology of panic disorder ; however , the role of norepinephrine has been more challenging to ascertain . The aim of this study was to determine the efficacy and tolerability of reboxetine , a novel selective norepinephrine reuptake inhibitor , in patients with panic disorder with and without agoraphobia . METHOD Eighty-two patients ( aged 18 - 65 years ) with DSM-III-R panic disorder , with or without agoraphobia , were r and omly assigned to receive 6 to 8 mg/day of reboxetine ( 42 patients ) or placebo ( 40 patients ) for 8 weeks in this placebo-controlled , parallel-group , double-blind clinical trial . RESULTS Of the 82 patients enrolled in the trial , 75 were considered in the analysis ( 37 patients in the reboxetine group and 38 patients in the placebo group ) . At last assessment , there was a significant reduction in the mean number of panic attacks ( range , 9.3 - 1.2 ) and phobic symptoms ( range , 8.1 - 3.2 ) in the reboxetine group compared with the placebo group ( ranges , 8.5 - 5.8 and 7.7 - 5.2 , respectively ; p Hamilton Rating Scale for Depression , Hopkins Symptom Checklist-90 , and Sheehan Disability Scale scores were also greater in the reboxetine group compared with the placebo group . Adverse events reported more frequently with reboxetine than placebo included dry mouth ( 36 % vs. 16 % ) , constipation ( 27 % vs. 22 % ) , and insomnia ( 26 % vs. 22 % ) . CONCLUSION Reboxetine was effective and well tolerated in the treatment of panic disorder", "BACKGROUND Serotonin Selective Re-uptake Inhibitors ( SSRIs ) are the drugs of choice for treating panic disorder ( PD ) . In vitro studies have shown different pharmacodynamic profiles for SSRIs , but their clinical relevance is still unknown . Paroxetine , the SSRI with the strongest serotonergic effect , also shows significant cholinergic and noradrenergic activities . In this class of drugs , citalopram is the most selective for serotonin . We compared these two drugs and their effectiveness and tolerability in a sample of patients with PD in a two-month treatment course . METHOD Fifty-eight patients with PD were r and omly assigned to either the paroxetine or the citalopram treatment group in a single-blind , r and omized design . Each patient was assessed at days 0 , 7 and 60 by the Panic Associated Symptoms Scale ( PASS ) , the Sheehan Disability Scale ( SDS ) and the Fear Question naire ( FQ ) . Primary outcome measures were the percentage of patients free of panic attacks , anticipatory anxiety and phobic avoidance in the last week of the trial and the percentage of good responders , as defined by a reduction of at least 50 % from baseline of both PASS and SDS global scores at day 60 . RESULTS At day 60 , 86 % of patients receiving citalopram and 84 % of those receiving paroxetine responded well to treatment . No significant differences between the two drugs were found . Both were well tolerated , although sexual side effects and weight gain were frequent . Anticipatory anxiety decreased significantly after the first week of treatment , and no initial worsening in the panic attacks was observed . CONCLUSION Paroxetine and citalopram show similar anti-panic properties and a good tolerability profile . Our results support evidence that the serotonergic system plays a significant role in the anti-panic properties of these two SSRIs", "OBJECTIVE Several classes of medications have demonstrated efficacy in panic disorder , but direct comparison of 2 proven treatments is still uncommon . The purpose of this study was to compare sertraline and paroxetine in the acute treatment of panic disorder . METHOD Adult out patients with panic disorder with or without agoraphobia ( DSM-IV and ICD-10 criteria ) were r and omly assigned in double-blind fashion to 12 weeks of treatment with flexible doses of sertraline ( titrated up to 50 - 150 mg/day ; N = 112 ) or paroxetine ( titrated up to 40 - 60 mg/day ; N = 113 ) . Patients were then tapered off medication over 3 weeks . The primary analysis was a noninferiority analysis of Panic and Agoraphobia Scale ( PAS ) scores . Secondary measures included panic attack frequency and the Clinical Global Impressions-Improvement scale ( CGI-I ) ( with responders defined as those with a CGI-I score Sertraline and paroxetine were associated with equivalent levels of improvement on the PAS total score , as well as on all secondary outcome measures . Eighty-two percent of patients taking sertraline versus 78 % of those taking paroxetine were CGI-I responders at endpoint . Numerically more patients on paroxetine treatment compared with sertraline treatment discontinued due to adverse events ( 18 % vs. 12 % ; NS ) , and a significantly higher proportion of paroxetine patients showed > or = 7 % weight gain ( 7 % vs. proportion of panic-free patients increased by 4 % with sertraline but decreased by 11 % with paroxetine ( p Sertraline and paroxetine had equivalent efficacy in panic disorder , but sertraline was significantly better tolerated and was associated with significantly less clinical worsening during taper than paroxetine", "Inositol is a simple polyol precursor in a second messenger system important in the brain . Cerebrospinal fluid inositol has been reported as decreased in depression . A double-blind controlled trial of 12 g daily of inositol in 28 depressed patients for four weeks was performed . Significant overall benefit for inositol compared to placebo was found at week 4 on the Hamilton Depression Scale . No changes were noted in hematology , kidney or liver function . Since many antidepressants are effective in panic disorder , twenty-one patients with panic disorder with or without agoraphobia completed a double-blind , placebo-controlled , four week , r and om-assignment crossover treatment trial of inositol 12 g per day . Frequency and severity of panic attacks and severity of agoraphobia declined significantly with inositol compared to placebo . Side-effects were minimal . Since serotonin re-uptake inhibitors benefit obsessive compulsive disorder ( OCD ) and inositol is reported to reverse desensitization of serotonin receptors , thirteen patients with OCD completed a double-blind controlled crossover trial of 18 g inositol or placebo for six weeks each . Inositol significantly reduced scores of OCD symptoms compared with placebo . A controlled double-blind crossover trial of 12 g daily of inositol for a month in twelve anergic schizophrenic patients , did not show any beneficial effects . A double-blind controlled crossover trial of 6 g of inositol daily vs. glucose for one month each was carried out in eleven Alzheimer patients , with on clearly significant therapeutic effects . Antidepressant drugs have been reported to improve attention deficit disorder ( ADDH ) with hyperactivity symptomatology . We studied oral inositol in children with ADDH in a double-blind , crossover , placebo-controlled manner . Eleven children , mean age 8.9 + /- 3.6 years were enrolled in an eight week trial of inositol or placebo at a dose of 200 mg/kg body weight . Results show a trend for aggravation of the syndrome with myo-inositol as compared to placebo . Recent studies suggest that serotonin re-uptake inhibitors are helpful in at least some symptoms of autism . However a controlled double-blind crossover trial of inositol 200 mg/kg per day showed no benefit in nine children with autism . Cholinergic agonists have been reported to ameliorate electroconvulsive therapy (ECT)-induced memory impairment . Inositol metabolism is involved in the second messenger system for several muscarinic cholinergic receptors . Inositol 6 g daily was given in a crossover-double-blind manner for five days before the fifth or sixth ECT to a series of twelve patients , without effect . These results suggest that inositol has therapeutic effects in the spectrum of illness responsive to serotonin selective re-uptake inhibitors , including depression , panic and OCD , and is not beneficial in schizophrenia , Alzheimer 's ADDH , autism or ECT-induced cognitive impairment" ]	41189726-06ff-11f0-808a-c43d1ab1c353
Current guidelines on secondary prevention of cardiovascular disease recommend nurse-coordinated care ( NCC ) as an effective intervention . However , NCC programmes differ widely and the efficacy of NCC components has not been studied . To investigate the efficacy of NCC and its components in secondary prevention of coronary heart disease by means of a systematic review and meta- analysis of r and omised controlled trials . 18 r and omised trials ( 11 195 patients in total ) using 15 components of NCC met the predefined inclusion criteria . These components were placed into three main intervention strategies : ( 1 ) risk factor management ( 13 studies ) ; ( 2 ) multidisciplinary consultation ( 11 studies ) and ( 3 ) shared decision making ( 10 studies ) . Six trials combined NCC components from all three strategies . In total , 30 outcomes were observed . We summarised observed outcomes in four outcome categories : ( 1 ) risk factor levels ( 16 studies ) ; ( 2 ) clinical events ( 7 studies ) ; ( 3 ) patient-perceived health ( 7 studies ) and ( 4 ) guideline adherence ( 3 studies ) . Compared with usual care , NCC lowered systolic blood pressure ( weighted mean difference ( WMD ) 2.96 mm Hg ; 95 % CI 1.53 to 4.40 mm Hg ) and low-density lipoprotein cholesterol ( WMD 0.23 mmol/L ; 95 % CI 0.10 to 0.36 mmol/L ) . NCC also improved smoking cessation rates by 25 % ( risk ratio 1.25 ; 95 % CI 1.08 to 1.43 ) . NCC demonstrated to have an effect on a small number of outcomes . NCC that incorporated blood pressure monitoring , cholesterol control and smoking cessation has an impact on the improvement of secondary prevention . Additionally , NCC is a heterogeneous concept . A shared definition of NCC may facilitate better comparisons of NCC content and outcomes	[ "BACKGROUND Recent clinical trials have shown that modification of plasma lipoprotein concentrations can favorably alter progression of coronary atherosclerosis , but no data exist on the effects of a comprehensive program of risk reduction involving both changes in lifestyle and medications . This study tested the hypothesis that intensive multiple risk factor reduction over 4 years would significantly reduce the rate of progression of atherosclerosis in the coronary arteries of men and women compared with subjects r and omly assigned to the usual care of their physician . METHODS AND RESULTS Three hundred men ( n = 259 ) and women ( n = 41 ) ( mean age , 56 + /- 7.4 years ) with angiographically defined coronary atherosclerosis were r and omly assigned to usual care ( n = 155 ) or multifactor risk reduction ( n = 145 ) . Patients assigned to risk reduction were provided individualized programs involving a low-fat and -cholesterol diet , exercise , weight loss , smoking cessation , and medications to favorably alter lipoprotein profiles . Computer-assisted quantitative coronary arteriography was performed at baseline and after 4 years . The main angiographic outcome was the rate of change in the minimal diameter of diseased segments . All subjects underwent medical and risk factor evaluations at baseline and yearly for 4 years , and reasons for all hospitalizations and deaths were documented . Of the 300 subjects r and omized , 274 ( 91.3 % ) completed a follow-up arteriogram , and 246 ( 82 % ) had comparative measurements of segments with visible disease at baseline and follow-up . Intensive risk reduction result ed in highly significant improvements in various risk factors , including low-density lipoprotein cholesterol and apolipoprotein B ( both , 22 % ) , high-density lipoprotein cholesterol ( + 12 % ) , plasma triglycerides ( -20 % ) , body weight ( -4 % ) , exercise capacity ( + 20 % ) , and intake of dietary fat ( -24 % ) and cholesterol ( -40 % ) compared with relatively small changes in the usual-care group . No change was observed in lipoprotein(a ) in either group . The risk-reduction group showed a rate of narrowing of diseased coronary artery segments that was 47 % less than that for subjects in the usual-care group ( change in minimal diameter , -0.024 + /- 0.066 mm/y versus -0.045 + /- 0.073 mm/y ; P deaths occurred in each group . There were 25 hospitalizations in the risk-reduction group initiated by clinical cardiac events compared with 44 in the usual-care group ( rate ratio , 0.61 ; P = .05 ; 95 % confidence interval , 0.4 to 0.9 ) . CONCLUSIONS Intensive multifactor risk reduction conducted over 4 years favorably altered the rate of luminal narrowing in coronary arteries of men and women with coronary artery disease and decreased hospitalizations for clinical cardiac events", "Abstract Objective : To evaluate the effects of secondary prevention clinics run by nurses in general practice on the health of patients with coronary heart disease . Design : R and omised controlled trial of clinics over one year with assessment by self completed postal question naires and audit of medical records at the start and end of the trial . Setting : R and om sample of 19 general practice s in northeast Scotl and . Subjects : 1173 patients ( 685 men and 488 women ) under 80 years with working diagnoses of coronary heart disease who did not have terminal illness or dementia and were not housebound . Intervention : Clinic staff promoted medical and lifestyle aspects of secondary prevention and offered regular follow up . Main outcome measures : Health status measured by the SF-36 question naire , chest pain by the angina type specification , and anxiety and depression by the hospital anxiety and depression scale . Use of health services before and during the study . Results : There were significant improvements in six of eight health status domains ( all functioning scales , pain , and general health ) among patients attending the clinic . Role limitations attributed to physical problems improved most ( adjusted difference 8.52 , 95 % confidence interval 4.16 to 12.9 ) . Fewer patients reported worsening chest pain ( odds ratio 0.59 , 95 % confidence interval 0.37 to 0.94 ) . There were no significant effects on anxiety or depression . Fewer intervention group patients required hospital admissions ( 0.64 , 0.48 to 0.86 ) , but general practitioner consultation rates did not alter . Conclusions : Within their first year secondary prevention clinics improved patients ' health and reduced hospital admissions . Key messages Nurse led clinics in general practice were used to promote secondary prevention to patients with coronary heart disease Within the first year the health of patients invited to the clinics improved Most benefit was in functional status , but chest pain improved too There was no effects on anxiety or depression There were significant reductions in hospital admissions in the first", "Commercial weight loss programs such as Weight Watchers ( WW ) offer widely recognized and accessible treatment , but typically produce weight losses that are modest relative to professionally delivered programs . This study tested the hypothesis that a novel weight loss approach that combined the fundamental components of professionally delivered behavioral weight loss ( BWL ) treatment with the existing WW program would produce better weight losses than WW alone ; no differences were expected between the novel treatment and BWL alone . Participants were 141 overweight and obese adults ( 90 % women , 67 % non-White , mean age = 49.7 ± 9.2 years , mean BMI = 36.2 ± 5.5 kg/m2 ) r and omly assigned to 48 weeks of BWL , 48 weeks of WW , or 12 weeks of BWL followed by 36 weeks of WW ( Combined Treatment , CT ) . Assessment s were conducted at baseline and weeks 12 , 24 , and 48 , with weight change as the primary outcome . Linear mixed model analysis showed that 24-week weight losses did not differ significantly between treatment groups ; however , weight losses at 48 weeks were greater in the WW group ( M=6.0 kg , SE=0.8 ) compared to the CT group ( M=3.6 kg , SE=0.8 ; p=0.032 ) , with BWL not significantly different from either ( M=5.4 kg , SE=0.8 ) . Further , a greater proportion of WW participants lost 10 % of baseline weight by 48 weeks compared to BWL or CT ( 36.7 % , 13.0 % , and 15.2 % , respectively , p’s the WW program can produce clinical ly meaningful weight losses and provides no evidence that adding brief BWL to the WW program improves outcome ", "Summary Background The increasing prevalence of overweight and obesity needs effective approaches for weight loss in primary care and community setting s. We compared weight loss with st and ard treatment in primary care with that achieved after referral by the primary care team to a commercial provider in the community . Methods In this parallel group , non-blinded , r and omised controlled trial , 772 overweight and obese adults were recruited by primary care practice s in Australia , Germany , and the UK . Participants were r and omly assigned with a computer-generated simple r and omisation sequence to receive either 12 months of st and ard care as defined by national treatment guidelines , or 12 months of free membership to a commercial programme ( Weight Watchers ) , and followed up for 12 months . The primary outcome was weight change over 12 months . Analysis was by intention to treat ( last observation carried forward [ LOCF ] and baseline observation carried forward [ BOCF ] ) and in the population who completed the 12-month assessment . This trial is registered , number IS RCT N85485463 . Findings 377 participants were assigned to the commercial programme , of whom 230 ( 61 % ) completed the 12-month assessment ; and 395 were assigned to st and ard care , of whom 214 ( 54 % ) completed the 12-month assessment . In all analyses , participants in the commercial programme group lost twice as much weight as did those in the st and ard care group . Mean weight change at 12 months was −5·06 kg ( SE 0·31 ) for those in the commercial programme versus −2·25 kg ( 0·21 ) for those receiving st and ard care ( adjusted difference −2·77 kg , 95 % CI −3·50 to −2·03 ) with LOCF ; −4·06 kg ( 0·31 ) versus −1·77 kg ( 0·19 ; adjusted difference −2·29 kg , −2·99 to −1·58 ) with BOCF ; and −6·65 kg ( 0·43 ) versus −3·26 kg ( 0·33 ; adjusted difference −3·16 kg , −4·23 to −2·11 ) for those who completed the 12-month assessment . Participants reported no adverse events related to trial participation . Interpretation Referral by a primary health-care professional to a commercial weight loss programme that provides regular weighing , advice about diet and physical activity , motivation , and group support can offer a clinical ly useful early intervention for weight management in overweight and obese people that can be delivered at large scale . Funding Weight Watchers International , through a grant to the UK Medical Research Council", "Objective To evaluate whether nurse run clinics in general practice improve secondary prevention in patients with coronary heart disease . Design R and omised controlled trial . Setting A r and om sample of 19 general practice s in northeast Scotl and . Patients 1173 patients ( 685 men and 488 women ) under 80 years with working diagnoses of coronary heart disease , but without terminal illness or dementia and not housebound . Intervention Nurse run clinics promoted medical and lifestyle aspects of secondary prevention and offered regular follow up . Main outcome measures Components of secondary prevention assessed at baseline and one year were : aspirin use ; blood pressure management ; lipid management ; physical activity ; dietary fat ; and smoking status . A cumulative score was generated by counting the number of appropriate components of secondary prevention for each patient . Results There were significant improvements in aspirin management ( odds ratio 3.22 , 95 % confidence interval 2.15 to 4.80 ) , blood pressure management ( 5.32 , 3.01 to 9.41 ) , lipid management ( 3.19 , 2.39 to 4.26 ) , physical activity ( 1.67 , 1.23 to 2.26 ) and diet ( 1.47 , 1.10 to 1.96 ) . There was no effect on smoking cessation ( 0.78 , 0.47 to 1.28 ) . Of six possible components of secondary prevention , the baseline mean was 3.27 . The adjusted mean improvement attributable to intervention was 0.55 of a component ( 0.44 to 0.67 ) . Improvement was found regardless of practice baseline performance . Conclusions Nurse run clinics proved practical to implement in general practice and effectively increased secondary prevention in coronary heart disease . Most patients gained at least one effective component of secondary prevention and , for them , future cardiovascular events and mortality could be reduced by up to a third", "BACKGROUND Disease management programs ( DMPs ) that use multidisciplinary teams and specialized clinics reduce hospital admissions and improve quality of life and functional status . Evaluations of cardiac DMPs delivered by home health nurses are required . METHODS Between August 1999 and August 2000 we identified consecutive patients admitted to hospital with elevated cardiac enzymes . Patients who agreed were r and omly assigned to participate in a DMP or to receive usual care . The DMP included 6 home visits by a cardiac-trained nurse , a st and ardized nurses ' checklist , referral criteria for specialty care , communication with the family physician and patient education . We measured readmission days per 1000 follow-up days for angina , congestive heart failure ( CHF ) and chronic obstructive pulmonary disease ( COPD ) ; all-cause readmission days ; and provincial cl aims for emergency department visits , physician visits , diagnostic or therapeutic services and laboratory services . RESULTS We screened 715 consecutive patients admitted with elevated cardiac markers between August 1999 and August 2000 . Of those screened 71 DMP and 75 usual care patients met the diagnostic criteria for myocardial infa rct ion , were eligible for visits from a home health nurse and consented to participate in the study . Readmission days for angina , CHF and COPD per 1000 follow-up days were significantly higher for usual care patients than for DMP patients ( incidence density ratio [ IDR ] = 1.59 , 95 % confidence interval [ CI ] 1.27 - 2.00 , p All-cause readmission days per 1000 follow-up days were significantly higher for usual care patients than for DMP patients ( IDR = 1.53 , 95 % CI 1.37 - 1.71 , p difference in emergency department encounters per 1000 follow-up days was significant ( IDR = 2.08 , 95 % CI 1.56 - 2.77 , p DMP patients than for usual care patients for emergency department visits ( p = 0.007 ) , diagnostic or therapeutic services ( p = 0.012 ) and laboratory services ( p = 0.007 ) . INTERPRETATION The results provide evidence that an appropriately developed and implemented community-based inner-city DMP delivered by home health nurses has a positive impact on patient outcomes", "Background —We examined the impact of a prolonged secondary prevention program on recurrent hospitalization in cardiac patients with private health insurance . Methods and Results —The Young at Heart multicenter , r and omized , controlled trial compared usual postdischarge care ( UC ) with nurse-led , home-based intervention ( HBI ) . The primary end point was rate of all-cause hospital stay ( 31.5±7.5 months follow-up ) . In total , 602 patients ( aged 70±10 years , 72 % men ) were r and omized to UC ( n=296 ) or HBI ( n=306 , 96 % received ≥1 home visit ) . Overall , 42 patients ( 7.0 % ) died , and 492 patients ( 82 % ) accumulated 2397 all-cause hospitalizations associated with 10 258 hospital days costing > $ 17 million . There were minimal group differences ( HBI versus UC ) in the primary end point of all-cause hospital stay ( 5405 versus 4853 days ; median [ interquartile range ] , 0.08 [ 0.03–0.17 ] versus 0.07 [0.03–0.13]/patient per month ) . There were similar trends with respect to all hospitalizations ( 1197 versus 1200 ; P=0.802 ) and associated costs ( $ 8.66 versus $ 8.58 million ; P=0.375 ) . At 2 years , however , more HBI versus UC ( 39 % versus 27 % ; odds ratio , 1.67 ; 95 % confidence interval , 1.15–2.41 ; P=0.007 ) patients were assessed as stable and optimally managed . For women , HBI outcomes were predominantly worse than UC outcomes . In men , HBI was associated with reduced risk of cardiovascular hospitalization ( adjusted hazard ratio , 0.68 ; 95 % confidence interval , 0.46–0.99 ; P=0.044 ) with less cardiovascular hospitalizations ( 192 versus 269 ; P=0.054 ) and costs ( $ 2.49 versus $ 3.53 million ; P=0.046 ) . Conclusions —HBI did not reduce recurrent all-cause hospitalization compared with UC in privately insured cardiac patients overall . However , it did convey some benefits in cardiac outcomes for men . Clinical Trial Registration —Australian New Zeal and Clinical Trials Registry Unique Identifier : 12608000014358 . URL : http://www.anzctr.org.au/trial_view.aspx?id=82509", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "Objective To assess the effectiveness of a range of weight management programmes in terms of weight loss . Design Eight arm r and omised controlled trial . Setting Primary care trust in Birmingham , Engl and . Participants 740 obese or overweight men and women with a comorbid disorder identified from general practice records . Interventions Weight loss programmes of 12 weeks ’ duration : Weight Watchers ; Slimming World ; Rosemary Conley ; group based , dietetics led programme ; general practice one to one counselling ; pharmacy led one to one counselling ; choice of any of the six programmes . The comparator group was provided with 12 vouchers enabling free entrance to a local leisure ( fitness ) centre . Main outcome measures The primary outcome was weight loss at programme end ( 12 weeks ) . Secondary outcomes were weight loss at one year , self reported physical activity , and percentage weight loss at programme end and one year . Results Follow-up data were available for 658 ( 88.9 % ) participants at programme end and 522 ( 70.5 % ) at one year . All programmes achieved significant weight loss from baseline to programme end ( range 1.37 kg ( general practice ) to 4.43 kg ( Weight Watchers ) ) , and all except general practice and pharmacy provision result ed in significant weight loss at one year . At one year , only the Weight Watchers group had significantly greater weight loss than did the comparator group ( 2.5 ( 95 % confidence interval 0.8 to 4.2 ) kg greater loss , ) . The commercial programmes achieved significantly greater weight loss than did the primary care programmes at programme end ( mean difference 2.3 ( 1.3 to 3.4 ) kg ) . The primary care programmes were the most costly to provide . Participants allocated to the choice arm did not have better outcomes than those r and omly allocated to a programme . Conclusions Commercially provided weight management services are more effective and cheaper than primary care based services led by specially trained staff , which are ineffective . Trial registration Current Controlled Trials IS RCT N25072883", "Abstract Objective : To assess the effectiveness of three different methods of promoting secondary prevention of coronary heart disease in primary care . Design : Pragmatic , unblinded , cluster r and omised controlled trial . Setting : Warwickshire . Subjects : 21 general practice s received intervention ; outcome measured in 1906 patients aged 55 - 75 years with established coronary heart disease . Interventions : Audit of notes with summary feedback to primary health care team ( audit group ) ; assistance with setting up a disease register and systematic recall of patients to general practitioner ( GP recall group ) ; assistance with setting up a disease register and systematic recall of patients to a nurse led clinic ( nurse recall group ) . Main outcome measures : At 18 months ' follow up : adequate assessment ( defined ) of 3 risk factors ( blood pressure , cholesterol , and smoking status ) ; prescribing of hypotensive agents , lipid lowering drugs , and antiplatelet drugs ; blood pressure , serum cholesterol level , and plasma cotinine levels . Results : Adequate assessment of all 3 risk factors was much more common in the nurse and GP recall groups ( 85 % , 76 % ) than the audit group ( 52 % ) . The advantage in the nurse recall compared with the audit group was 33 % ( 95 % confidence interval 19 % to 46 % ) ; in the GP recall group compared with the audit group 23 % ( 10 % to 36 % ) , and in the nurse recall group compared with the GP recall group 9 % ( −3 % to 22 % ) . However , these differences in assessment were not reflected in clinical outcomes . Mean blood pressure ( 148/80 , 147/81 , 148/81 mm Hg ) , total cholesterol ( 5.4 , 5.5 , 5.5 mmol/l ) , and cotinine levels ( % probable smokers 17 % , 16 % , 19 % ) varied little between the nurse recall , GP recall , and audit groups respectively , as did prescribing of hypotensive and lipid lowering agents . Prescribing of antiplatelet drugs was higher in the nurse recall group ( 85 % ) than the GP recall or audit groups ( 80 % , 74 % ) . After adjustment for baseline levels , the advantage in the nurse recall group compared with the audit group was 10 % ( 3 % to 17 % ) , in the nurse recall group compared with the GP recall group 8 % ( 1 % to 15 % ) and in the GP recall group compared with the audit group 2 % ( −6 % to 10 % ) . Conclusions : Setting up a register and recall system improved patient assessment at 18 months ' follow up but was not consistently better than audit alone in improving treatment or risk factor levels . Underst and ing the reasons for this is the key next step in improving the quality of care of patients with coronary heart disease . What is already known on this topic Effective preventive care of patients with any chronic disease requires planned and quality assured follow up on the basis of an up to date register Strategies for changing clinical practice in primary care have been of limited effectiveness What this study adds Setting up a coronary heart disease register for a practice substantially increases follow up and adequate assessment of patients at risk Improved assessment and follow up does not necessarily improve clinical outcome Follow up by nurses is as effective as , and may be more effective than , follow up by doctors Patients are being followed up and adequately assessed without the recommended preventive drugs being", "Background Transition from hospital to home is a critical period for older persons with acute myocardial infa rct ion ( AMI ) . Home-based secondary prevention programs led by nurses have been proposed to facilitate the patients ’ adjustment to AMI after discharge . The objective of this study was to evaluate the effects of a nurse-based case management for elderly patients discharged after an AMI from a tertiary care hospital . Methods In a single-centre r and omized two-armed parallel group trial of patients aged 65 years and older hospitalized with an AMI between September 2008 and May 2010 in the Hospital of Augsburg , Germany , patients were r and omly assigned to a case management or a control group receiving usual care . The case-management intervention consisted of a nurse-based follow-up for one year including home visits and telephone calls . Key elements of the intervention were to detect problems or risks and to give advice regarding a wide range of aspects of disease management ( e.g. nutrition , medication ) . Primary study endpoint was time to first unplanned readmission or death . Block r and omization per telephone call to a biostatistical center , where the r and omization list was kept , was performed . Persons who assessed one-year outcomes and vali date d readmission data were blinded . Statistical analysis was based on the intention-to-treat approach and included Cox Proportional Hazards models . Results Three hundred forty patients were allocated to receive case-management ( n=168 ) or usual care ( n=172 ) . The analysis is based on 329 patients ( intervention group : n=161 ; control group : n=168 ) . Of these , 62 % were men , mean age was 75.4 years , and 47.1 % had at least either diabetes or chronic heart failure as a major comorbidity . The mean follow-up time for the intervention group was 273.6 days , and for the control group it was 320.6 days . During one year , in the intervention group there were 57 first unplanned readmissions and 5 deaths , while the control group had 75 first unplanned readmissions and 3 deaths . With respect to the endpoint there was no significant effect of the case management program after one year ( Hazard Ratio 1.01 , 95 % confidence interval 0.72 - 1.41 ) . This was also the case among subgroups according to sex , diabetes , living alone , and comorbidities . Conclusions A nurse-based management among elderly patients with AMI had no significant influence on the rate of first unplanned readmissions or death during a one-year follow-up . A possible long-term influence should be investigated by further studies . Clinical trial registration IS RCT", "Objective To quantify the impact of a practical , hospital-based nurse-coordinated prevention programme on cardiovascular risk , integrated into the routine clinical care of patients discharged after an acute coronary syndrome , as compared with usual care only . Design RESPONSE ( R and omised Evaluation of Secondary Prevention by Outpatient Nurse SpEcialists ) was a r and omised clinical trial . Setting Multicentre trial in secondary and tertiary healthcare setting s. Participants 754 patients admitted for acute coronary syndrome . Intervention A nurse-coordinated prevention programme , consisting of four outpatient nurse clinic visits , focusing on healthy lifestyles , biometric risk factors and medication adherence , in addition to usual care . Main outcome measures The main outcome was 10-year cardiovascular mortality risk as estimated by Systematic Coronary Risk Evaluation at 12 months follow-up . Secondary outcomes included Framingham Coronary Risk Score at 12 months , in addition to changes in individual risk factors . Risk factor control was classified as ‘ poor ’ if 0 to 3 factors were on target , ‘ fair ’ if 4 to 6 factors were on target , and ‘ good ’ if 7 to 9 were on target . Results The mean Systematic Coronary Risk Evaluation at 12 months was 4.4 per cent ( SD 4.5 ) in the intervention group and 5.4 per cent ( SD 6.2 ) in the control group ( p=0.021 ) , representing a 17.4 % relative risk reduction . At 12 months , risk factor control classified as ‘ good ’ was achieved in 35 % of patients in the intervention group compared with 25 % in the control group ( p=0.003 ) . Attendance to the nurse-coordinated prevention programme was 92 % . In the intervention group , 86 rehospitalisations were observed against 132 in the control group ( relative risk reduction 34.8 % , p=0.023 ) . Conclusions The nurse-coordinated hospital-based prevention programme in addition to usual care is a practical , yet effective method for reduction of cardiovascular risk in patients with coronary disease . Our data suggest that the counselling component of the programme may lead to a reduction in hospital readmissions . Trial Registration trialregister.nl Identifier TC1290", "OBJECTIVE : To examine the ability of a secondary prevention programme to improve the lifestyle in myocardial infa rct ion patients aged 50 - 70 years . DESIGN : Habitual physical activity , food habits , and smoking habits were assessed from question naires at admission to hospital and at the one year follow up . Initially , all patients were invited to join an exercise programme and were informed about cardiovascular risk factors . Four weeks after discharge from the hospital , 87 patients were r and omised to follow up at the coronary prevention unit by a special trained nurse ( the intervention group ) , and 81 to follow up by their general practitioners ( the usual care group ) . After r and omisation , the intervention group was educated about the effects of smoking cessation , dietary management , and regular physical activity . The intervention group also participated in a physical training programme two to three times weekly for 10 - 12 weeks . MAIN RESULTS : 89 % of the patients referred to the intervention group improved their food habits compared with 62 % of the patients referred to the usual care group ( P = 0.008 ) . Furthermore , 50 % of the smokers referred to the intervention group stopped smoking compared to 29 % in the usual care group ( P = 0.09 ) . Changes in physical activity did not differ between the groups . CONCLUSIONS : This secondary prevention programme based on a nurse rehabilitator was successful in improving food habits in patients with acute myocardial infa rct ion . Initiating the smoking cessation programme during the hospital stay followed by repeated counselling during follow up might have improved the results . The exercise programme had no advantage in supporting physical activity compared to usual care", "In a trial to evaluate the effectiveness of a nurse-directed intervention design ed to help patients decrease dietary intake of fat , quit or decrease smoking , and increase exercise , 138 women who underwent coronary artery bypass surgery were r and omized to receive special intervention ( SI ) or usual care ( UC ) . The SI group received a behavioral program based on self-efficacy theory in the home 2 weeks after discharge with regular follow-up . The UC group received routine medical care . Risk factors and lifestyle behaviors were measured at baseline and 1 year after surgery in 116 ( 84 % ) women ( SI = 59 , UC = 57 ) . The SI group decreased their total fat intake from a mean of 38 % of calories at baseline to 35 % at 1 year , while the UC group increased it from 36 % to 38 % . The prevalence of smoking decreased from 24 % at baseline to 8 % at 1 year in the SI group and from 19 % to 14 % in the UC group . At follow-up , the quit rate in those smoking at baseline was 64 % in the SI group , with no new smokers , and 55 % in the UC group , with three new smokers . Both groups reported improvement in exercise , with the proportion of women reporting participation in some form of regular exercise slightly higher in the SI group than in the UC group , 54 % and 51 % , respectively", "BACKGROUND A substantial part of cardiovascular disease prevention is delivered in primary care . Special attention should be paid to the assessment of cardiovascular risk factors . According to the Dutch guideline for cardiovascular risk management , the heavy workload of cardiovascular risk management for GPs could be shared with advanced practice nurses . AIM To investigate the clinical effectiveness of practice nurses acting as substitutes for GPs in cardiovascular risk management after 1 year of follow-up . DESIGN OF STUDY Prospect i ve pragmatic r and omised trial . SETTING Primary care in the south of the Netherl and s. Six centres ( 25 GPs , six nurses ) participated . METHOD A total of 1626 potentially eligible patients at high risk for cardiovascular disease were r and omised to a practice nurse group ( n = 808 ) or a GP group ( n = 818 ) in 2006 . In total , 701 patients were included in the trial . The Dutch guideline for cardiovascular risk management was used as the protocol , with st and ardised techniques for risk assessment . Changes in the following risk factors after 1 year were measured : lipids , systolic blood pressure , and body mass index . In addition , patients in the GP group received a brief question naire . RESULTS A larger decrease in the mean level of risk factors was observed in the practice nurse group compared with the GP group . After controlling for confounders , only the larger decrease in total cholesterol in the practice nurse group was statistically significant ( P = 0.01 , two-sided ) . CONCLUSION Advanced practice nurses are achieving results , equal to or better than GPs for the management of risk factors . The findings of this study support the involvement of practice nurses in cardiovascular risk management in Dutch primary care", "OBJECTIVE To assess the effectiveness of a programme to coordinate and support follow up care in general practice after a hospital diagnosis of myocardial infa rct ion or angina . DESIGN R and omised controlled trial ; stratified r and om allocation of practice s to intervention and control groups . SETTING All 67 practice s in Southampton and south west Hampshire , Engl and . SUBJECTS 597 adult patients ( 422 with myocardial infa rct ion and 175 with a new diagnosis of angina ) who were recruited during hospital admission or attendance at a chest pain clinic between April 1995 and September 1996 . INTERVENTION Programme to coordinate preventive care led by specialist liaison nurses which sought to improve communication between hospital and general practice and to encourage general practice nurses to provide structured follow up . MAIN OUTCOME MEASURES Serum total cholesterol concentration , blood pressure , distance walked in 6 minutes , confirmed smoking cessation , and body mass index measured at 1 year follow up . RESULTS Of 559 surviving patients at 1 year , 502 ( 90 % ) were followed up . There was no significant difference between the intervention and control groups in smoking ( cotinine vali date d quit rate 19 % v 20 % ) , lipid concentrations ( serum total cholesterol 5.80 v 5.93 mmol/l ) , blood pressure ( diastolic pressure 84 v 85 mm Hg ) , or fitness ( distance walked in 6 minutes 443 v 433 m ) . Body mass index was slightly lower in the intervention group ( 27.4 v 28.2 ; P=0.08 ) . CONCLUSIONS Although the programme was effective in promoting follow up in general practice , it did not improve health outcome . Simply coordinating and supporting existing NHS care is insufficient . Ischaemic heart disease is a chronic condition which requires the same systematic approach to secondary prevention applied in other chronic conditions such as diabetes mellitus", "AIM The aim of this study was to examine the effect of a cardiac rehabilitation programme on health behaviours and physiological risk parameters in patients with coronary heart disease in Chengdu , China . BACKGROUND Epidemiological studies indicate a dose- , level- and duration -dependent relationship exists between cardiac behavioural and physiological risks and coronary heart disease incidence as well as subsequent cardiac morbidity and mortality . Cardiac risk factor modification has become the very primary goal of modern cardiac rehabilitation programmes . DESIGN METHODS A r and omized controlled trial was conducted . Coronary heart disease patients ( n = 167 ) who met the sampling criteria in two tertiary medical centres in Chengdu , south-west China , were r and omly assigned to either an intervention group ( the cardiac rehabilitation programme ) or control group ( the routine care ) . The change of health behaviours ( walking performance , step II diet adherence , medication adherence , smoking cessation ) and physiological risk parameters ( serum lipids , blood pressure , body weight ) were assessed to evaluate the programme effect . RESULTS Patients in the intervention group demonstrated a significantly better performance in walking , step II diet adherence , medication adherence ; a significantly greater reduction in serum lipids including triglyceride , total cholesterol , low-density lipoprotein ; and significantly better control of systolic and diastolic blood pressure at three months . The majority of these positive impacts were maintained at six months . The effect of the programme on smoking cessation , body weight , serum high-density lipoprotein , was not confirmed . CONCLUSIONS A cardiac rehabilitation programme led by a nurse can significantly improve the health behaviours and cardiac physiological risk parameters in coronary heart disease patients . Nurses can fill significant treatment gaps in the risk factor management of patients with coronary heart disease . RELEVANCE TO CLINICAL PRACTICE This study raises attention regarding the important roles nurses can play in cardiac rehabilitation and the unique way for nurses to meet the rehabilitative care needs of coronary heart disease patients . Furthermore , the hospital-home bridging nature of the programme also created a model for interfacing the acute care and community rehabilitative care", "Background —Despite well-publicized guidelines on the appropriate management of cardiovascular disease and type 2 diabetes , the implementation of risk-reducing practice s remains poor . This report describes the results of a r and omized , controlled clinical trial evaluating the effectiveness of a comprehensive program of cardiovascular disease risk reduction delivered by nurse practitioner /community health worker ( NP/CHW ) teams versus enhanced usual care ( EUC ) to improve lipids , blood pressure , glycated hemoglobin ( HbA1c ) , and patient perceptions of the quality of their chronic illness care in patients in urban community health centers . Methods and Results —A total of 525 patients with documented cardiovascular disease , type 2 diabetes , hypercholesterolemia , or hypertension and levels of LDL cholesterol , blood pressure , or HbA1c that exceeded goals established by national guidelines were r and omly assigned to NP/CHW ( n=261 ) or EUC ( n=264 ) groups . The NP/CHW intervention included aggressive pharmacological management and tailored educational and behavioral counseling for lifestyle modification and problem solving to address barriers to adherence and control . Compared with EUC , patients in the NP/CHW group had significantly greater 12-month improvement in total cholesterol ( difference , 19.7 mg/dL ) , LDL cholesterol ( difference,15.9 mg/dL ) , triglycerides ( difference , 16.3 mg/dL ) , systolic blood pressure ( difference , 6.2 mm Hg ) , diastolic blood pressure ( difference , 3.1 mm Hg ) , HbA1c ( difference , 0.5 % ) , and perceptions of the quality of their chronic illness care ( difference , 1.2 points ) . Conclusions —An intervention delivered by an NP/CHW team using individualized treatment regimens based on treat-to-target algorithms can be an effective approach to improve risk factor status and perceptions of chronic illness care in high-risk patients . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00241904", "This study examined whether nurses could manage coronary risk factors in patients with unstable angina more effectively than physicians practicing usual care . Three hundred twenty-six patients were r and omized in the emergency room to a 6-month program of risk factor management by a registered nurse versus participation in usual care . The nurse intervention consisted of a 30-minute counseling visit at 6 to 10 days after the chest pain episode and a second 30-minute session 1 month later . Multiple risk factors were assessed and addressed : smoking , blood lipids , blood pressure , blood glucose , physical inactivity , weight , psychological stress , and social isolation . Compared with usual care , nurse intervention patients significantly reduced both triglycerides ( -29 + /- 8 vs 5 + /- 6 mg/dl ; p weight ( -0.9 + /- 3.3 vs + 0.1 + /- 2.1 kg ; p = 0.0071 ) , and had corresponding improvements in self-reported diet compliance and exercise ( + 34 + /- 106 vs + 9 + /- 98 minutes , p = 0.0491 ) . No significant differences between groups were observed in terms of 6-month changes in total , high-density lipoprotein , or low-density lipoprotein cholesterol , blood pressure , fasting blood glucose , percent body fat or waist-hip ratio , or psychological distress scores . The 6-month rate of recurrent events ( cardiac death , out-of-hospital cardiac arrest , myocardial infa rct ion ) and /or revascularizations ( coronary artery bypass surgery or coronary angioplasty ) was lower in the nurse intervention group ( 1 % vs 9 % ; p = 0.002 ) . We conclude that a nurse-delivered risk factor intervention program for patients with chest pain is feasible and more effective than usual care in terms of fostering lifestyle changes that may lower coronary risk", "Table . SI Units Systematic modification of coronary risk factors is not integrated into the medical care provided to most of the more than 1 million patients treated annually in the United States for acute myocardial infa rct ion by percutaneous transluminal coronary angioplasty or coronary artery surgery . Most of such patients have lipoprotein abnormalities [ 1 ] , and nearly one half smoke [ 2 ] . These risk factors , which contribute to subsequent morbidity and mortality , remain highly prevalent after acute cardiac events . Failure to integrate comprehensive risk factor modification into the st and ard medical care provided to patients after acute cardiac events primarily reflects the lack of an organizational framework or system . This deficiency in re source allocation for preventive and rehabilitative aspects of care in turn reflects the predominant orientation of the U.S. health care system to the management of acute illness [ 3 ] . Several clinical research studies have shown the effectiveness of risk factor modification , especially treatment of lipoprotein abnormalities [ 4 - 7 ] , in achieving regression of coronary artery lesions and reducing the clinical consequences of coronary artery disease [ 6 , 7 ] . However , risk factor interventions shown to be effective in clinical trials may not prove equally effective in clinical practice because of a paucity of re sources , especially nonphysician personnel . The lack of effective management systems limits the expected reduction in morbidity and mortality and the corresponding reduction in medical care costs that motivates current efforts to orient the priorities of the American health care system toward preventive and rehabilitative care . This r and omized , controlled trial compared the effectiveness of a physician-directed , nurse-managed , home-based case-management system for coronary risk factor modification with that of usual medical care . Outcomes were measured in both groups immediately after the end of the first year after acute myocardial infa rct ion . The term case-management system has been used in various context s. As used here , it refers to a system in which a nurse case-manager , working with different health care specialists ( a psychiatrist , a cardiologist , a lipid specialist , a nutritionist , and a nurse coordinator ) , managed coronary risk factors . Methods Enrollment and Orientation Program nurses enlisted patients on hospital day 3 or as soon as their medical condition stabilized . Study participants gave written informed consent to be r and omly assigned to a treatment group . Immediately after r and omization , program nurses introduced patients to the special intervention with the aid of a videotape . Usual Care The 585 patients in our study were cared for by 215 internists and 34 cardiologists in the five participating medical centers who were organized into practice groups of 5 to 10 physicians each . Cardiology consultation was often provided during hospitalization , but primary responsibility for follow-up care was generally assumed by internists . The usual care offered by the Kaiser Permanente Medical Care Program included physician counseling on smoking cessation and nutritionist counseling on dietary change during hospitalization and physician-managed , lipid-lowering drug therapy after hospital discharge . Group outpatient smoking cessation programs were available for a $ 50 fee . Group exercise rehabilitation , not generally provided by the Kaiser Permanente Medical Care Program during this study , was available to patients at various community facilities at an average cost of $ 1800 to $ 2700 for 3 months ' participation . Special Intervention The behavioral interventions in our case-management system , which were offered to the 293 patients in the intervention group in addition to usual care , were derived from social learning theory [ 8 , 9 ] and modified for medical problems [ 10 ] . In this model , persons must learn how to monitor the health habits they seek to change , set attainable sub goals to motivate and direct their efforts , use feedback of progress in ways that promote health , and enlist incentives and social support to sustain the effort needed to succeed [ 8 , 9 ] . In the hospital , patients were instructed on how to complete self-reports [ status reports ] of smoking , dietary intake , and exercise . Scheduled interactions between case managers and patients after discharge took three forms : 1 ) nurse-initiated telephone contacts ; 2 ) computer-generated progress reports mailed to patients based on question naires completed by patients and mailed to the nurses ; and 3 ) visits to the program nurse for treadmill exercise testing , initiation of lipid-lowering drug therapy , if indicated , and a single counseling session after a smoking relapse . The maximum number of treatment contacts during the year , including outcome measurement at 6 and 12 months , was as follows : 14 nurse-initiated telephone contacts , 8 patient visits to the blood chemistry laboratory , and 4 patient visits to the nurse case manager . Smoking Intervention Smoking was defined as the use of cigarettes , cigars , cigarillos , pipe tobacco , or any other form of tobacco in the 6 months before admission . Forty-three percent of patients were smokers . Patients who had smoked during the 6 months before hospitalization received the same intensive smoking cessation intervention during hospitalization ; this intervention has been described previously [ 11 ] . Physicians used a written script that enabled them to provide st and ardized counseling in less than 2 minutes . The hospital-based smoking cessation counseling focused on relapse prevention . Nurses conducted a st and ardized smoking history to evaluate patients ' addiction to smoking . Patients ' reported self-efficacy or confidence to resist smoking in each of 28 potentially high-risk situations was measured ; patients were then counseled on how to manage the situations in which they reported less than 70 % confidence . Patients also received a relapse prevention manual and a relaxation audiotape . They were advised that the nurse would telephone them 48 hours and 1 week after hospital discharge and at monthly intervals for as long as 6 months . Patients who relapsed were offered one additional visit with the nurse for further counseling . Nicotine polacrilex or transdermal nicotine patches were reserved for highly addicted patients who relapsed after hospital discharge . Nutritional Counseling A computer-based expert system developed by the investigators was used to provide nutritional counseling on a National Cholesterol Education Program [ 12 ] Step 2 diet that was low in cholesterol and saturated fat . A food frequency question naire design ed by the investigators was scored using the Cholesterol and Saturated Fat Index developed by Connor and colleagues [ 13 ] . Calculations of cholesterol and saturated fat totals were based on weekly rather than daily average food intakes . Data from the food frequency question naires , mailed by patients to the Stanford coordinating center and entered into a microcomputer , were used to generate progress reports that characterized patients ' dietary patterns , prioritized dietary change goals , and provided guides for managing difficult situations by directing patients to relevant sections of a nutrition workbook entitled Good Eating for Good Health developed by the program nutritionist . Patients in the intervention group completed a food frequency question naire during hospitalization that described their eating habits in the previous month . Patients also completed food frequency question naires 6 , 11 , and 26 weeks after admission . Progress reports were mailed to patients within 48 to 72 hours after the food frequency question naires were received . Detailed strategies for maintenance of dietary change were incorporated into the 26-week progress report . Question naires to evaluate outcomes were also completed at 36 and 52 weeks . Lipid-Lowering Drug Therapy The therapeutic goal of a plasma low-density lipoprotein (LDL)-cholesterol value of 2.46 mmol/L ( 95 mg/dL ) adopted for this trial was based on the mean post-treatment level of LDL cholesterol found in patients in the study by Blankenhorn and colleagues [ 4 ] . Patients with mean plasma LDL cholesterol values ( based on measurements in two separate blood sample s drawn 75 and 90 days after infa rct ion ) that exceeded this value were given initial drug therapy according to the four algorithms shown in Table 1 . Patients unable to tolerate bile acid-binding resin or nicotinic acid because of comorbid conditions or potentially adverse interactions with these agents received lovastatin or gemfibrozil . During a visit 90 days after discharge , the nurses did a brief physical examination and obtained a history relevant to hyperlipidemia . They provided detailed counseling to patients regarding the rationale for lipid-lowering drug therapy and ways to maximize drug efficacy and minimize drug side effects , and they advised patients on the schedule of laboratory visits and nurse-initiated follow-up telephone contacts . Table 1 . Initial Drug Therapy * Changes in drug therapy at 120 , 150 , and 180 days , which were coordinated by nurse-initiated telephone contacts , were based on three types of responses to initial therapy : 1 ) if lipoprotein levels returned to normal , the effective drug therapy was continued ; 2 ) if the response was incomplete , the dose of the effective medication was increased or another drug was added , or both ; and 3 ) if comorbid conditions worsened or blood chemistry abnormalities or intolerable side effects occurred , drug dosage was reduced or the patient was switched to another agent or both . A physician lipid specialist and a Stanford-based senior nurse-coordinator provided telephone consultation to the case managers . Before initiating lipid-lowering drug therapy at 90 days and at each subsequent step , nurses review ed the patients ' blood chemistry and lipoprotein values and elicited any symptoms requiring a change in therapy . The", "Cost and accessibility contribute to low participation rates in phase 2 cardiac rehabilitation programs in the United States . In this study , we compared the clinical effectiveness of 2 less costly and potentially more accessible approaches to cardiovascular risk reduction with that of a contemporary phase 2 cardiac rehabilitation program . Low- or moderate-risk patients ( n = 155 ) with coronary artery disease ( CAD ) were r and omly assigned to 12 weeks of participation in a contemporary phase 2 cardiac rehabilitation program ( n = 52 ) , a physician supervised , nurse-case-managed cardiovascular risk reduction program ( n = 54 ) , or a community-based cardiovascular risk reduction program administered by exercise physiologists guided by a computerized participant management system based on national clinical guidelines ( n = 49 ) . In all , 142 patients ( 91.6 % ) completed testing at baseline and after 12 weeks of intervention . For patients with abnormal ( i.e. , not at the goal level ) baseline values , statistically significant ( p multiple CAD risk factors . No statistically significant risk factor differences were observed among the 3 programs . For patients with a baseline maximal oxygen uptake metabolic equivalents , cardiorespiratory fitness increased to a greater degree in patients in the cardiac rehabilitation program and the community-based program versus the physician-supervised , nurse- case-managed program . These data have important implication s for cost containment and increasing accessibility to clinical ly effective comprehensive cardiovascular risk reduction services in low- or moderate-risk patients with CAD", "BACKGROUND Despite the large body of evidence confirming the effectiveness of lipid lowering for the secondary prevention of coronary heart disease ( CHD ) events , undertreatment of hyperlipidemia is common . This study tested the effectiveness of a nurse case management program to lower blood lipids in patients with CHD . METHODS A total of 228 consecutive , eligible adults with hypercholesterolemia and CHD were recruited during hospitalization after coronary revascularization . Patients were r and omized to receive lipid management , including individualized lifestyle modification and pharmacologic intervention , from a nurse practitioner for 1 year after discharge in addition to their usual care ( NURS ) , or to usual care enhanced with feedback on lipids to their primary provider and /or cardiologist ( EUC ) . RESULTS Significantly more patients in the NURS group than in the EUC group achieved low-density lipoprotein cholesterol ( LDL-C ) levels changes in lipids and lipoproteins were accompanied by significant improvements in dietary and exercise patterns in the NURS group . In a multivariate analysis adjusting for other covariates , being assigned to the NURS group ( P = .0001 ) and being on a lipid-lowering medication ( P = .001 ) were significant independent predictors of LDL-C level . CONCLUSIONS Control of hypercholesterolemia in patients who have undergone coronary revascularization can be improved by a nurse case-management program . Because the National Cholesterol Education Program Adult Treatment Panel III guidelines have broadened the definition of high-risk population s that warrant aggressive treatment , nurse case-management programs may offer key opportunities to enhance appropriate application of new treatment paradigms", "Aims : To evaluate the effect of a disease management programme for patients with coronary heart disease ( CHD ) and chronic heart failure ( CHF ) in primary care . Methods : A cluster r and omised controlled trial of 1316 patients with CHD and CHF from 20 primary care practice s in the UK was carried out . Care in the intervention practice s was delivered by specialist nurses trained in the management of patients with CHD and CHF . Usual care was delivered by the primary healthcare team in the control practice s. Results : At follow up , significantly more patients with a history of myocardial infa rct ion in the intervention group were prescribed a beta-blocker compared to the control group ( adjusted OR 1.43 , 95 % CI 1.19 to 1.99 ) . Significantly more patients with CHD in the intervention group had adequate management of their blood pressure ( cholesterol ( diagnosis of left ventricular systolic dysfunction confirmed ( OR 4.69 , 95 % CI 1.88 to 11.66 ) or excluded ( OR 3.80 , 95 % CI 1.50 to 9.64 ) in the intervention group compared to the control group . There were significant improvements in some quality -of-life measures in patients with CHD in the intervention group . Conclusions : Disease management programmes can lead to improvements in the care of patients with CHD and presumed CHF in primary care", "BACKGROUND Our aim was to investigate whether a nurse-coordinated multidisciplinary , family-based preventive cardiology programme could improve st and ards of preventive care in routine clinical practice . METHODS In a matched , cluster-r and omised , controlled trial in eight European countries , six pairs of hospitals and six pairs of general practice s were assigned to an intervention programme ( INT ) or usual care ( UC ) for patients with coronary heart disease or those at high risk of developing cardiovascular disease . The primary endpoints-measured at 1 year-were family-based lifestyle change ; management of blood pressure , lipids , and blood glucose to target concentrations ; and prescription of cardioprotective drugs . Analysis was by intention to treat . The trial is registered as IS RCT N 71715857 . FINDINGS 1589 and 1499 patients with coronary heart disease in hospitals and 1189 and 1128 at high risk were assigned to INT and UC , respectively . In patients with coronary heart disease who smoked in the month before the event , 136 ( 58 % ) in the INT and 154 ( 47 % ) in the UC groups did not smoke 1 year afterwards ( difference in change 10.4 % , 95 % CI -0.3 to 21.2 , p=0.06 ) . Reduced consumption of saturated fat ( 196 [ 55 % ] vs 168 [ 40 % ] ; 17.3 % , 6.4 to 28.2 , p=0.009 ) , and increased consumption of fruit and vegetables ( 680 [ 72 % ] vs 349 [ 35 % ] ; 37.3 % , 18.1 to 56.5 , p=0.004 ) , and oily fish ( 156 [ 17 % ] vs 81 [ 8 % ] ; 8.9 % , 0.3 to 17.5 , p=0.04 ) at 1 year were greatest in the INT group . High-risk individuals and partners showed changes only for fruit and vegetables ( p=0.005 ) . Blood-pressure target of less than 140/90 mm Hg was attained by both coronary ( 615 [ 65 % ] vs 547 [ 55 % ] ; 10.4 % , 0.6 to 20.2 , p=0.04 ) and high-risk ( 586 [ 58 % ] vs 407 [ 41 % ] ; 16.9 % , 2.0 to 31.8 , p=0.03 ) patients in the INT groups . Achievement of total cholesterol of less than 5 mmol/L did not differ between groups , but in high-risk patients the difference in change from baseline to 1 year was 12.7 % ( 2.4 to 23.0 , p=0.02 ) in favour of INT . In the hospital group , prescriptions for statins were higher in the INT group ( 810 [ 86 % ] vs 794 [ 80 % ] ; 6.0 % , -0.5 to 11.5 , p=0.04 ) . In general practice s in the intervention groups , angiotensin-converting enzyme inhibitors ( 297 [ 29 % ] INT vs 196 [ 20 % ] UC ; 8.5 % , 1.8 to 15.2 , p=0.02 ) and statins ( 381 [ 37 % ] INT vs 232 [ 22 % ] UC ; 14.6 % , 2.5 to 26.7 , p=0.03 ) were more frequently prescribed . INTERPRETATION To achieve the potential for cardiovascular prevention , we need local preventive cardiology programmes adapted to individual countries , which are accessible by all hospitals and general practice s caring for coronary and high-risk patients", "BACKGROUND Coronary heart disease is the major cause of illness and death in Western countries and this is likely to increase as the average age of the population rises . Consumers with established coronary heart disease are at the highest risk of experiencing further coronary events . Lifestyle measures can contribute significantly to a reduction in cardiovascular mortality in established coronary heart disease . Improved management of cardiac risk factors by providing education and referrals as required has been suggested as one way of maintaining quality care in patients with established coronary heart disease . There is a need to ascertain whether or not nurse-led clinics would be an effective adjunct for patients with coronary heart disease to supplement general practitioner advice and care . OBJECTIVES The objective of this review was to present the best available evidence related to nurse-led cardiac clinics . INCLUSION CRITERIA This review considered any r and omised controlled trials that evaluated cardiac nurse-led clinics . In the absence of r and omised controlled trials , other research design s such as non-r and omised controlled trials and before and after studies were considered for inclusion . Participants were adults ( 18 years and older ) with new or existing coronary heart disease . The interventions of interest to the review included education , assessment , consultation , referral and administrative structures . Outcomes measured included adverse event rates , readmissions , admissions , clinical and cost effectiveness , consumer satisfaction and compliance with therapy . RESULTS Based on the search terms used , 80 papers were initially identified and review ed for inclusion ; full reports of 24 of these papers were retrieved . There were no papers included that addressed cost effectiveness or adverse events ; and none addressed the outcome of referrals . A critical appraisal of the 24 remaining papers identified a total of six r and omised controlled trials that met the inclusion criteria . Two studies addressed nurse-led clinics for patients diagnosed with angina , one looked at medication administration and the other looked at educational plans . A further four studies compared secondary preventative care with a nurse-led clinic and general practitioner clinic . One specifically compared usual care versus shared care introduced by nurses for patients awaiting coronary artery bypass grafting . Of the remaining three studies , two have been combined in the results section , as they are an interim report and a final report of the same study . Because of inconsistencies in reporting styles and outcome measurements , meta- analysis could not be performed on all outcomes . However , a narrative summary of each study and comparisons of specific outcomes assessed from within each study has been developed . Although not all outcomes obtained statistical significance , nurse-led clinics were at least as effective as general practitioner clinics for most outcomes . Recommendations The following recommendations are made" ]	41189762-06ff-11f0-808a-c43d1ab1c353
BACKGROUND The optimal rhythm management strategy for people with non-paroxysmal ( persistent or long-st and ing persistent ) atrial fibrilation is currently not well defined . Antiarrhythmic drugs have been the mainstay of therapy . But recently , in people who have not responded to antiarrhythmic drugs , the use of ablation ( catheter and surgical ) has emerged as an alternative to maintain sinus rhythm to avoid long-term atrial fibrillation complications . However , evidence from r and omised trials about the efficacy and safety of ablation in non-paroxysmal atrial fibrillation is limited . OBJECTIVES To determine the efficacy and safety of ablation ( catheter and surgical ) in people with non-paroxysmal ( persistent or long-st and ing persistent ) atrial fibrillation compared to antiarrhythmic drugs . SEARCH METHODS We search ed the Cochrane Central Register of Controlled Trials ( CENTRAL ) , MEDLINE Ovid , Embase Ovid , conference abstract s , clinical trial registries , and Health Technology Assessment Data base . We search ed these data bases from their inception to 1 April 2016 . We used no language restrictions . SELECTION CRITERIA We included r and omised trials evaluating the effect of radiofrequency catheter ablation ( RFCA ) or surgical ablation compared with antiarrhythmic drugs in adults with non-paroxysmal atrial fibrillation , regardless of any concomitant underlying heart disease , with at least 12 months of follow-up . DATA COLLECTION AND ANALYSIS Two review authors independently selected studies and extracted data . We evaluated risk of bias using the Cochrane ' Risk of bias ' tool . We calculated risk ratios ( RRs ) for dichotomous data with 95 % confidence intervals ( CIs ) a using fixed-effect model when heterogeneity was low ( I² 40 % ) . Using the GRADE approach , we evaluated the quality of the evidence and used the GRADE profiler ( GRADE pro ) to import data from Review Manager 5 to create ' Summary of findings ' tables . MAIN RESULTS We included three r and omised trials with 261 participants ( mean age : 60 years ) comparing RFCA ( 159 participants ) to antiarrhythmic drugs ( 102 ) for non-paroxysmal atrial fibrillation . We generally assessed the included studies as having low or unclear risk of bias across multiple domains , with reported outcomes generally lacking precision due to low event rates . Evidence showed that RFCA was superior to antiarrhythmic drugs in achieving freedom from atrial arrhythmias ( RR 1.84 , 95 % CI 1.17 to 2.88 ; 3 studies , 261 participants ; low- quality evidence ) , reducing the need for cardioversion ( RR 0.62 , 95 % CI 0.47 to 0.82 ; 3 studies , 261 participants ; moderate- quality evidence ) , and reducing cardiac-related hospitalisation ( RR 0.27 , 95 % CI 0.10 to 0.72 ; 2 studies , 216 participants ; low- quality evidence ) at 12 months follow-up . There was substantial uncertainty surrounding the effect of RFCA regarding significant bradycardia ( or need for a pacemaker ) ( RR 0.20 , 95 % CI 0.02 to 1.63 ; 3 studies , 261 participants ; low- quality evidence ) , periprocedural complications , and other safety outcomes ( RR 0.94 , 95 % CI 0.16 to 5.68 ; 3 studies , 261 participants ; very low- quality evidence ) . AUTHORS ' CONCLUSIONS In people with non-paroxysmal atrial fibrillation , evidence suggests a superiority of RFCA to antiarrhythmic drugs in achieving freedom from atrial arrhythmias , reducing the need for cardioversion , and reducing cardiac-related hospitalisations . There was uncertainty surrounding the effect of RFCA with significant bradycardia ( or need for a pacemaker ) , periprocedural complications , and other safety outcomes . Evidence should be interpreted with caution , as event rates were low and quality of evidence ranged from moderate to very low	[ "Background — Data regarding the long-term efficacy of atrial fibrillation ( AF ) ablation are still lacking . Methods and Results —Two hundred four consecutive patients symptomatic for paroxysmal or persistent/permanent AF were r and omly assigned to 2 different ablation schemes : pulmonary vein isolation ( PVI ) and PVI plus left linear lesions ( LL ) . Primary end point was to assess the maintenance of sinus rhythm ( SR ) after procedures 1 and 2 in the absence of antiarrhythmic drugs in a long-term follow-up of at least 3 years . Paroxysmal AF — With a single procedure at 12-month follow-up , 46 % of patients treated with PVI maintained SR , whereas at 3-year follow-up , 29 % were in SR ; using the “ PVI plus LL ” at the 12-month follow-up , 57 % of patients were in SR , whereas at the 3-year follow-up , 53 % remained in SR . After a second procedure , the long-term overall success rate without antiarrhythmic drugs was 62 % with PVI and 85 % with PVI plus LL . Persistent/Permanent AF — With a single procedure at the 12-month follow-up , 27 % of patients treated with PVI were in SR , whereas at the 3-year follow-up , 19 % maintained SR ; using the PVI plus LL with a single procedure at the 12-month follow-up 45 % of patients were in SR , whereas at the 3-year follow-up , 41 % remained in SR . After a second procedure , the long-term overall success rate without antiarrhythmic drugs was 39 % with PVI and 75 % with PVI plus LL . Conclusions —A long-term follow-up of AF ablation shows that short-term results can not be considered permanent because AF recurrences are still present after the first year especially in patients who have had “ PVI ” strategy . PVI isolation plus LL is superior to the PVI strategy in maintaining SR without antiarrhythmic drugs after procedures 1 and 2 both in paroxysmal and persistent AF", "OBJECTIVES This study sought to assess the safety and effectiveness of a novel cryoballoon ablation technology design ed to achieve single-delivery pulmonary vein ( PV ) isolation . BACKGROUND St and ard radiofrequency ablation is effective in eliminating atrial fibrillation ( AF ) but requires multiple lesion delivery at the risk of significant complications . METHODS Patients with documented symptomatic paroxysmal AF and previously failed therapy with ≥ 1 membrane active antiarrhythmic drug underwent 2:1 r and omization to either cryoballoon ablation ( n = 163 ) or drug therapy ( n = 82 ) . A 90-day blanking period allowed for optimization of antiarrhythmic drug therapy and reablation if necessary . Effectiveness of the cryoablation procedure versus drug therapy was determined at 12 months . RESULTS Patients had highly symptomatic AF ( 78 % paroxysmal , 22 % early persistent ) and experienced failure of at least one antiarrhythmic drug . Cryoablation produced acute isolation of three or more PVs in 98.2 % and all four PVs in 97.6 % of patients . PVs isolation was achieved with the balloon catheter alone in 83 % . At 12 months , treatment success was 69.9 % ( 114 of 163 ) of cryoblation patients compared with 7.3 % of antiarrhythmic drug patients ( absolute difference , 62.6 % [ p recurrent , symptomatic AF , constituting drug treatment failure . There were 7 of the result ing 228 cryoablated patients ( 3.1 % ) with a > 75 % reduction in PV area during 12 months of follow-up . Twenty-nine of 259 procedures ( 11.2 % ) were associated with phrenic nerve palsy as determined by radiographic screening ; 25 of these had resolved by 12 months . Cryoablation patients had significantly improved symptoms at 12 months . CONCLUSIONS The STOP AF trial demonstrated that cryoballoon ablation is a safe and effective alternative to antiarrhythmic medication for the treatment of patients with symptomatic paroxysmal AF , for whom at least one antiarrhythmic drug has failed , with risks within accepted st and ards for ablation therapy . ( A Clinical Study of the A rct ic Front Cryoablation Balloon for the Treatment of Paroxysmal Atrial Fibrillation [ Stop AF ] ; NCT00523978 )", "BACKGROUND The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation ( MANTRA-PAF ) is a r and omized trial comparing radiofrequency catheter ablation ( RFA ) to antiarrhythmic drugs ( AADs ) as first-line treatment of paroxysmal atrial fibrillation ( PAF ) . In order to eliminate the clouding effect of crossover we performed an on-treatment analysis of the data . METHODS AND RESULTS Patients ( n=294 ) were divided into three groups : those receiving only the assigned therapy ( RFA and AAD groups ) and those receiving both therapies ( crossover group ) . The primary end points were AF burden in 7-day Holter recordings at 3 , 6 , 12 , 18 , and 24 months and cumulative AF burden in all recordings . At 24 months , AF burden was significantly lower in the RFA ( n=110 ) than in the AAD ( n=92 ) and the crossover ( n=84 ) groups ( 90th percentile 1 % vs. 10 % vs. 16 % , P=0.007 ) , and more patients were free from any AF ( 89 % vs. 73 % vs. 74 % , P=0.006 ) . In the RFA , AAD and the crossover groups 63 % , 59 % and 21 % ( P no AF episodes in any Holter recording , respectively . Quality of life improved significantly in all groups . There were no differences in serious adverse events between the RFA , AAD and crossover groups ( 19 % vs. 8 % vs. 23 % ) ( P=0.10 ) . CONCLUSIONS In the treatment of antiarrhythmic therapy naïve patients with PAF long-term efficacy of RFA was superior to AAD therapy . Thus , it is reasonable to offer RFA as first-line treatment for highly symptomatic patients who accept the risks of the procedure and are aware of frequent need for reablation(s )", "CONTEXT Treatment with antiarrhythmic drugs and anticoagulation is considered first-line therapy in patients with symptomatic atrial fibrillation ( AF ) . Pulmonary vein isolation ( PVI ) with radiofrequency ablation may cure AF , obviating the need for antiarrhythmic drugs and anticoagulation . OBJECTIVE To determine whether PVI is feasible as first-line therapy for treating patients with symptomatic AF . DESIGN , SETTING , AND PARTICIPANTS A multicenter prospect i ve r and omized study conducted from December 31 , 2001 , to July 1 , 2002 , of 70 patients aged 18 to 75 years who experienced monthly symptomatic AF episodes for at least 3 months and had not been treated with antiarrhythmic drugs . INTERVENTION Patients were r and omized to receive either PVI using radiofrequency ablation ( n=33 ) or antiarrhythmic drug treatment ( n=37 ) , with a 1-year follow-up . MAIN OUTCOME MEASURES Recurrence of AF , hospitalization , and quality of life assessment . RESULTS Two patients in the antiarrhythmic drug treatment group and 1 patient in the PVI group were lost to follow-up . At the end of 1-year follow-up , 22 ( 63 % ) of 35 patients who received antiarrhythmic drugs had at least 1 recurrence of symptomatic AF compared with 4 ( 13 % ) of 32 patients who received PVI ( P Hospitalization during 1-year follow-up occurred in 19 ( 54 % ) of 35 patients in the antiarrhythmic drug group compared with 3 ( 9 % ) of 32 in the PVI group ( P antiarrhythmic drug group , the mean ( SD ) number of AF episodes decreased from 12 ( 7 ) to 6 ( 4 ) , after initiating therapy ( P = .01 ) . At 6-month follow-up , the improvement in quality of life of patients in the PVI group was significantly better than the improvement in the antiarrhythmic drug group in 5 subclasses of the Short-Form 36 health survey . There were no thromboembolic events in either group . Asymptomatic mild or moderate pulmonary vein stenosis was documented in 2 ( 6 % ) of 32 patients in the PVI group . CONCLUSION Pulmonary vein isolation appears to be a feasible first-line approach for treating patients with symptomatic AF . Larger studies are needed to confirm its safety and efficacy", "BACKGROUND Left atrial ( LA ) circumferential ablation has been reported to eliminate atrial fibrillation ( AF ) . Whether an ablation without encirclement of the pulmonary veins ( PVs ) is as effective as LA circumferential ablation is not clear . OBJECTIVES The purpose of this study was to compare the efficacy of LA circumferential ablation and nonencircling linear ablation in patients with chronic AF . METHODS Eighty patients with chronic AF were r and omized to undergo LA circumferential ablation ( n = 40 ) or nonencircling linear ablation ( n = 40 ) . In LA circumferential ablation , the PVs were encircled , with additional lines made in the mitral isthmus and posterior wall or roof . In nonencircling linear ablation , 4 + /- 1 ablation lines were created through areas of complex electrograms , with lines in the roof ( 38 ) , anterior wall ( 36 ) , septum ( 40 ) , mitral isthmus ( 32 ) , and posterior annulus ( 6 ) . The endpoint of LA circumferential ablation and nonencircling linear ablation was voltage abatement . RESULTS LA flutter occurred in 15 % after LA circumferential ablation and in 18 % after nonencircling linear ablation ( P = .8 ) . A repeat ablation procedure was performed for recurrent AF in 7 and 11 patients or for atrial flutter in 6 and 4 patients after LA circumferential ablation and nonencircling linear ablation , respectively ( P = .8 ) . At 9 + /- 4 months , the prevalence of AF was 28 % in the LA circumferential ablation and 25 % in the nonencircling linear ablation group ( P = .8 ) . Sixty-eight percent and 60 % of patients were in sinus rhythm and free of AF and atrial flutter in the absence of antiarrhythmic drug therapy after LA circumferential ablation and nonencircling linear ablation , respectively ( P = .5 ) . There were no complications . CONCLUSION Nonencircling linear ablation and LA circumferential ablation are equally efficacious in eliminating chronic AF . However , the advantage of nonencircling linear ablation is that it eliminates the need for ablation along the posterior wall of the LA . Therefore , nonencircling linear ablation may avoid the small but real risk of atrioesophageal fistula formation associated with LA circumferential ablation", "BACKGROUND This prospect i ve multicenter r and omized study aim ed to compare the efficacy of 3 common ablation methods used for longst and ing permanent atrial fibrillation ( AF ) . METHODS A total of 144 patients with longst and ing permanent AF ( median duration 28 months ) were r and omly assigned to circumferential pulmonary vein ablation ( CPVA , group 1 , n = 47 ) , to pulmonary vein antrum isolation ( PVAI , group 2 , n = 48 ) or to a hybrid strategy combining ablation of complex fractionated or rapid atrial electrograms ( CFAE ) in both atria followed by a pulmonary vein antrum isolation ( CFAE + PVAI , group 3 , n = 49 ) . RESULTS Scarring in the left atrium and structural heart disease/hypertension were present in most patients ( 65 % ) . After a mean follow-up of 16 months , 11 % of patients in group 1 , 40 % of patients in group 2 and 61 % of patients in group 3 were in sinus rhythm after one procedure and with no antiarrhythmic drugs ( P Sinus rhythm maintenance would increase respectively to 28 % ( group 1 ) , 83 % ( group 2 ) , and 94 % ( group 3 ) after 2 procedures and with antiarrhythmic drugs ( AADs , P conversion to sinus rhythm or organization into an atrial tachyarrhythmia , in 13 % of patients ( group 1 ) , 44 % ( group 2 ) , and 74 % ( group 3 ) respectively . CFAE alone , performed as the first step of the ablation in group 3 , organized AF in only 1 patient . CONCLUSION In this study , the hybrid AF ablation strategy including antrum isolation and CFAE ablation had the highest likelihood of maintaining sinus rhythm in patients with longst and ing permanent AF . Electrical isolation of the PVs , although inadequate if performed alone , is relevant to achieve long-term sinus rhythm maintenance after ablation . Bi-atrial CFAE ablation had a minimal impact on AF termination during ablation", "Objective To determine whether or not radiofrequency ablation ( RFA ) for persistent atrial fibrillation in patients with advanced heart failure leads to improvements in cardiac function . Setting Patients were recruited from heart failure outpatient clinics in Scotl and . Design and intervention Patients with advanced heart failure and severe left ventricular dysfunction were r and omised to RFA ( rhythm control ) or continued medical treatment ( rate control ) . Patients were followed up for a minimum of 6 months . Main outcome measure Change in left ventricular ejection fraction ( LVEF ) measured by cardiovascular MRI . Results 22 patients were r and omised to RFA and 19 to medical treatment . In the RFA group , 50 % of patients were in sinus rhythm at the end of the study ( compared with none in the medical treatment group ) . The increase in cardiovascular magnetic resonance ( CMR ) LVEF in the RFA group was 4.5±11.1 % compared with 2.8±6.7 % in the medical treatment group ( p=0.6 ) . The RFA group had a greater increase in radionuclide LVEF ( a prespecified secondary end point ) than patients in the medical treatment group ( + 8.2±12.0 % vs + 1.4±5.9 % ; p=0.032 ) . RFA did not improve N-terminal pro-B-type natriuretic peptide , 6 min walk distance or quality of life . The rate of serious complications related to RFA was 15 % . Conclusions RFA result ed in long-term restoration of sinus rhythm in only 50 % of patients . RFA did not improve CMR LVEF compared with a strategy of rate control . RFA did improve radionuclide LVEF but did not improve other secondary outcomes and was associated with a significant rate of serious complications . Clinical trials registration number NCT00292162", "Background — The mainstay of treatment for atrial fibrillation ( AF ) remains pharmacological ; however , catheter ablation has increasingly been used over the last decade . The relative merits of each strategy have not been extensively studied . Methods and Results — We conducted a r and omized multicenter comparison of these 2 treatment strategies in patients with paroxysmal AF resistant to at least 1 antiarrhythmic drug . The primary end point was absence of recurrent AF between months 3 and 12 , absence of recurrent AF after up to 3 ablation procedures , or changes in antiarrhythmic drugs during the first 3 months . Ablation consisted of pulmonary vein isolation in all cases , whereas additional extrapulmonary vein lesions were at the discretion of the physician . Crossover was permitted at 3 months in case of failure . Echocardiographic data , symptom score , exercise capacity , quality of life , and AF burden were evaluated at 3 , 6 , and 12 months by the supervising committee . Of 149 eligible patients , 112 ( 18 women [ 16 % ] ; age , 51.1±11.1 years ) were enrolled and r and omized to ablation ( n=53 ) or “ new ” antiarrhythmic drugs alone or in combination ( n=59 ) . Crossover from the antiarrhythmic drugs and ablation groups occurred in 37 ( 63 % ) and 5 patients ( 9 % ) , respectively ( P=0.0001 ) . At the 1-year follow-up , 13 of 55 patients ( 23 % ) and 46 of 52 patients ( 89 % ) had no recurrence of AF in the antiarrhythmic drug and ablation groups , respectively ( P were significantly higher in the ablation group . Conclusion — This r and omized multicenter study demonstrates the superiority of catheter ablation over antiarrhythmic drugs in patients with AF with regard to maintenance of sinus rhythm and improvement in symptoms , exercise capacity , and quality of life", "Background —Restoring sinus rhythm in patients with heart failure ( HF ) and atrial fibrillation ( AF ) may improve left ventricular ( LV ) function and HF symptoms . We sought to compare the effect of a catheter ablation strategy with that of a medical rate control strategy in patients with persistent AF and HF . Methods and Results — Patients with persistent AF , symptomatic HF , and LV ejection fraction catheter ablation or medical rate control . The primary end-point was the difference between groups in LV ejection fraction at 6 months . Baseline LV ejection fraction was 32±8 % in the ablation group and 34±12 % in the medical group . Twenty-six patients underwent catheter ablation , and 24 patients were rate controlled . Freedom from AF was achieved in 21/26 ( 81 % ) at 6 months off antiarrhythmic drugs . LV ejection fraction at 6 months in the ablation group was 40±12 % compared with 31±13 % in the rate control group ( P=0.015 ) . Ablation was associated with better peak oxygen consumption ( 22±6 versus 18±6 mL/kg per minute ; P=0.014 ) and Minnesota living with HF question naire score ( 24±22 versus 47±22 ; P=0.001 ) compared with rate control . Conclusions —Catheter ablation is effective in restoring sinus rhythm in selected patients with persistent AF and HF , and can improve LV function , functional capacity , and HF symptoms compared with rate control . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier :", "BACKGROUND The incidence of atrial fibrillation ( AF ) after ablation of a cavotricuspid isthmus (CTI)-dependent atrial flutter ( AFL ) is high . OBJECTIVE The purpose of this study was to test the hypothesis that AFL and AF may be initiated by pulmonary vein triggers . This prospect i ve r and omized trial tested the efficacy of a st and alone pulmonary vein isolation ( PVI ) in patients with AFL but without AF . METHODS Patients with AFL but without documented AF were r and omly assigned to 1 of 3 treatment groups : ( 1 ) antiarrhythmic drugs ( AAD ) , ( 2 ) CTI ablation , or ( 3 ) circumferential PVI . The primary end-point was defined as any recurrent atrial tachyarrhythmia and the secondary end-point as recurrence of AFL . In case of tachyarrhythmia recurrence in the PVI group , a second PVI was performed to close gaps in the ablation lines . RESULTS Of the 60 patients , 17 were r and omized to AAD , 23 to CTI ablation , and 20 to PVI . During follow-up of 1.42 ± 0.83 years , 14 of 17 patients ( 82.4 % ) in the AAD group , 14 of 23 patients ( 60.9 % ) in the CTI group , and 2 of 20 patients ( 10 % ) in the PVI group reached the primary end-point ( P AFL reoccurred in 9 patients ( 52.9.% ) in the AAD group , in 2 patients ( 8.7 % ) in the CTI group , and after a single PVI in 3 patients ( 15 % ) in the PVI group ( P = .003 ) . After closure of gaps , 1 patient ( 5 % ) in the PVI group presented with recurrent AFL . CONCLUSION Pulmonary vein triggers play an important role in AFL . PVI can prevent the recurrence of AFL , even without CTI ablation", "BACKGROUND We prospect ively compared the efficacy , safety , and quality of life ( QoL ) impact of catheter ablation versus antiarrhythmic drugs ( AAD ) in elderly patients with persistent atrial fibrillation ( AF ) . METHODS AND RESULTS Four hundred and twelve consecutive patients , aged ≥ 70 years , underwent ablation ( Group A , 153 patients ) or AAD ( Group B , 259 patients ) . Study endpoints : treatment failure ( any AF/AT lasting > 30 seconds ) and treatment-related adverse events ( acute when ≤1 month of procedure and long term when > 1 month ) . At a follow-up of 60 ± 17 months , 43 % and 46 % patients in Group B versus 58 % and 76 % in Group A were in sinus rhythm ( SR ) , respectively , after one ( P = 0.003 ) and 2 procedures ( P Fifteen acute adverse events occurred ( 6.7 % in Group A vs 1 % in Group B , P mainly periprocedural cerebral thromboembolism ( 3.3 % in Group A vs 0.7 % in Group B , P = 0.058 ) . Previous TIA/stroke result ed the only independent predictor of periprocedural cerebrovascular accidents ( OR 1.2 , 95%IC 1.1 - 1.3 ) . At follow-up , 74 long-term adverse events occurred ( 7.7 % in Group A vs 23.9 % in Group B , P AAD-related adverse events ( 12.7 % vs 2.6 % , P recurrences significantly improved QoL scores ( P elderly persistent AF patients , catheter ablation is more effective in maintaining SR and in improving QoL than AAD but is affected by a higher risk of embolic complications , particularly in patients with previous TIA/stroke . Over time , Group A patients more likely discontinued AAD with a reduction of long-term adverse events ", "AIMS The Atrial Fibrillation Ablation Pilot Study is a prospect i ve registry design ed to describe the clinical epidemiology of patients undergoing an atrial fibrillation ( AFib ) ablation , and the diagnostic/therapeutic processes applied across Europe . The aims of the 1-year follow-up were to analyse how centres assess in routine clinical practice the success of the procedure and to evaluate the success rate and long-term safety/complications . METHODS AND RESULTS Seventy-two centres in 10 European countries were asked to enrol 20 consecutive patients undergoing a first AFib ablation procedure . A web-based case report form captured information on pre-procedural , procedural , and 1-year follow-up data . Between October 2010 and May 2011 , 1410 patients were included and 1391 underwent an AFib ablation ( 98.7 % ) . A total of 1300 patients ( 93.5 % ) completed a follow-up control 367 ± 42 days after the procedure . Arrhythmia documentation was done by an electrocardiogram in 76 % , Holter-monitoring in 52 % , transtelephonic monitoring in 8 % , and /or implanted systems in 4.5 % . Over 50 % became asymptomatic . Twenty-one per cent were re-admitted due to post-ablation arrhythmias . Success without antiarrhythmic drugs was achieved in 40.7 % of patients ( 43.7 % in paroxysmal AF ; 30.2 % in persistent AF ; 36.7 % in long-lasting persistent AF ) . A second ablation was required in 18 % of the cases and 43.4 % were under antiarrhythmic treatment . Thirty-three patients ( 2.5 % ) suffered an adverse event , 272 ( 21 % ) experienced a left atrial tachycardia , and 4 patients died ( 1 haemorrhagic stroke , 1 ventricular fibrillation in a patient with ischaemic heart disease , 1 cancer , and 1 of unknown cause ) . CONCLUSION The AFib Ablation Pilot Study provided crucial information on the epidemiology , management , and outcomes of catheter ablation of AFib in a real-world setting . The methods used to assess the success of the procedure appeared at least suboptimal . Even in this context , the 12-month success rate appears to be somewhat lower to the one reported clinical trials", "Background —Early recurrence of atrial fibrillation ( ERAF ) is common after radiofrequency catheter ablation for AF . We sought to determine the incidence and prognostic significance of ERAF after cryoballoon ablation . Moreover , the benefit of early reablation for ERAF after cryoballoon ablation is undetermined . Methods and Results —The Sustained Treatment of Paroxysmal Atrial Fibrillation ( STOP AF ) trial r and omized 245 patients with paroxysmal AF to medical therapy versus cryoballoon-based pulmonary vein ablation . Patients were followed for 12 months . ERAF was defined as any recurrence of AF > 30 seconds during the first 3 months of follow-up . Late recurrence ( LR ) was defined as any recurrence of AF > 30 seconds between 3 and 12 months . Of the 163 patients r and omized to cryoablation , 84 patients experienced ERAF ( 51.5 % ) . The only significant factor associated with ERAF was male sex ( hazard ratio [ HR ] , 2.18 ; 95 % confidence interval [ CI ] , 1.03–4.61 ; P=0.041 ) . LR was observed in 41 patients ( 25.1 % ) , and was significantly related to ERAF ( 55.6 % LR with ERAF versus 12.7 % without ERAF ; P current tobacco use ( HR , 3.84 ; 95 % CI , 1.82–8.11 ; P with LR . Conversely , early reablation was associated with greater freedom from LR ( 3.3 % LR with early reablation versus 55.6 % without ; HR , 0.04 ; 95 % CI , 0.01–0.32 ; P=0.002 ) . Conclusions —ERAF after cryoballoon ablation occurs in ≈50 % of patients and is strongly associated with LR . Early reablation for ERAF is associated with excellent long-term freedom from recurrent AF", "Background Catheter ablation ( CA ) is a highly effective therapy for the treatment of paroxysmal atrial fibrillation ( AF ) when compared with antiarrhythmic drug therapy ( ADT ) . No r and omized studies have compared the two strategies in persistent AF . The present r and omized trial aim ed to compare the effectiveness of CA vs. ADT in treating persistent AF . Methods and results Patients with persistent AF were r and omly assigned to CA or ADT ( excluding patients with long-st and ing persistent AF ) . Primary endpoint at 12-month follow-up was defined as any episode of AF or atrial flutter lasting > 24 h that occurred after a 3-month blanking period . Secondary endpoints were any atrial tachyarrhythmia lasting > 30 s , hospitalization , and electrical cardioversion . In total , 146 patients were included ( aged 55 ± 9 years , 77 % male ) . The ADT group received class Ic ( 43.8 % ) or class III drugs ( 56.3 % ) . In an intention-to-treat analysis , 69 of 98 patients ( 70.4 % ) in the CA group and 21 of 48 patients ( 43.7 % ) in the ADT group were free of the primary endpoint ( P = 0.002 ) , implying an absolute risk difference of 26.6 % ( 95 % CI 10.0–43.3 ) in favour of CA . The proportion of patients free of any recurrence ( > 30 s ) was higher in the CA group than in the ADT group ( 60.2 vs. 29.2 % ; P 0.018 ) . Conclusion Catheter ablation is superior to medical therapy for the maintenance of sinus rhythm in patients with persistent AF at 12-month follow-up . Clinical Trial Registration Information NCT00863213 ( http:// clinical trials.gov/ct2/show/NCT00863213 )", "BACKGROUND We conducted a r and omized , controlled trial of circumferential pulmonary-vein ablation for the treatment of chronic atrial fibrillation . METHODS A total of 146 patients with a mean ( + /-SD ) age of 57+/-9 years who had chronic atrial fibrillation were r and omly assigned to receive amiodarone and undergo two cardioversions during the first three months alone ( the control group ) or in combination with circumferential pulmonary-vein ablation . Cardiac rhythm was assessed with daily telephonic transmissions for one year . The left atrial diameter and the severity of symptoms were assessed at 12 months . RESULTS Among the 77 patients assigned to undergo circumferential pulmonary-vein ablation , ablation was repeated because of recurrent atrial fibrillation in 26 percent of patients and atypical atrial flutter in 6 percent . An intention-to-treat analysis showed that 74 percent of patients in the ablation group and 58 percent of those in the control group were free of recurrent atrial fibrillation or flutter without antiarrhythmic-drug therapy at one year ( P=0.05 ) . Among the 69 patients in the control group , 53 ( 77 percent ) crossed over to undergo circumferential pulmonary-vein ablation for recurrent atrial fibrillation by one year and only 3 ( 4 percent ) were in sinus rhythm without antiarrhythmic-drug therapy or ablation . There were significant decreases in the left atrial diameter ( 12+/-11 percent , P symptom severity score ( 59+/-21 percent , P Sinus rhythm can be maintained long term in the majority of patients with chronic atrial fibrillation by means of circumferential pulmonary-vein ablation independently of the effects of antiarrhythmic-drug therapy , cardioversion , or both . The maintenance of sinus rhythm is associated with a significant decrease in both the severity of symptoms and the left atrial diameter", "OBJECTIVES We hypothesized that human atrial fibrillation ( AF ) may be sustained by localized sources ( electrical rotors and focal impulses ) , whose elimination ( focal impulse and rotor modulation [ FIRM ] ) may improve outcome from AF ablation . BACKGROUND Catheter ablation for AF is a promising therapy , whose success is limited in part by uncertainty in the mechanisms that sustain AF . We developed a computational approach to map whether AF is sustained by several me and ering waves ( the prevailing hypothesis ) or localized sources , then prospect ively tested whether targeting patient-specific mechanisms revealed by mapping would improve AF ablation outcome . METHODS We recruited 92 subjects during 107 consecutive ablation procedures for paroxysmal or persistent ( 72 % ) AF . Cases were prospect ively treated , in a 2-arm 1:2 design , by ablation at sources ( FIRM-guided ) followed by conventional ablation ( n = 36 ) , or conventional ablation alone ( n = 71 ; FIRM-blinded ) . RESULTS Localized rotors or focal impulses were detected in 98 ( 97 % ) of 101 cases with sustained AF , each exhibiting 2.1 ± 1.0 sources . The acute endpoint ( AF termination or consistent slowing ) was achieved in 86 % of FIRM-guided cases versus 20 % of FIRM-blinded cases ( p FIRM ablation alone at the primary source terminated AF in a median 2.5 min ( interquartile range : 1.0 to 3.1 min ) . Total ablation time did not differ between groups ( 57.8 ± 22.8 min vs. 52.1 ± 17.8 min , p = 0.16 ) . During a median 273 days ( interquartile range : 132 to 681 days ) after a single procedure , FIRM-guided cases had higher freedom from AF ( 82.4 % vs. 44.9 % ; p electrocardiography monitoring . Adverse events did not differ between groups . CONCLUSIONS Localized electrical rotors and focal impulse sources are prevalent sustaining mechanisms for human AF . FIRM ablation at patient-specific sources acutely terminated or slowed AF , and improved outcome . These results offer a novel mechanistic framework and treatment paradigm for AF . ( Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulation [ CONFIRM ] ; NCT01008722 )", "BACKGROUND The optimal ablation technique for persistent and long-st and ing persistent atrial fibrillation ( AF ) is unclear . Both linear lesion ( LL ) and ganglionated plexus ( GP ) ablation have been used in addition to pulmonary vein isolation ( PVI ) , but no direct comparison of the 2 methods exists . OBJECTIVE The aim of this study is to assess the comparative safety and efficacy of 2 different ablation strategies-PVI+LL vs PVI+GP ablation -in patients with persistent or long-st and ing persistent AF . METHODS Two hundred sixty-four consecutive patients with persistent/long-st and ing persistent AF were r and omly assigned to 2 different ablation schemes : PVI+LL ( n = 132 ) and PVI+GP ( n = 132 ) ablation . Consistent sinus rhythm ( SR ) off antiarrhythmic drug was assessed after follow-up of at least 3 years with the use of an implanted monitoring device . RESULTS All procedural end points were acutely achieved . At 12 months after a single procedure , 47 % of the patients treated with PVI+LL were in SR compared to 54 % of the patients treated with PVI+GP ( P = .29 ) . At 3 years , 34 % of the patients with PVI+LL and 49 % of the patients with PVI+GP maintained SR ( P = .035 ) . Atrial flutter was more frequent in the PVI+LL group than in PVI+GP group ( 18 % vs 6 % ; P = .002 ) . After a second procedure in 78 patients of the PVI+LL group and 55 patients of the PVI+GP group , the long-term overall success rate was 52 % and 68 % , respectively ( P = .006 ) . CONCLUSIONS PVI+GP ablation confers superior clinical results with less ablation-related left atrial flutter and reduced AF recurrence compared to PVI+LL ablation at 3 years of follow-up", "AIMS We conducted a multi-centre , prospect i ve , controlled , r and omized trial to investigate the adjunctive role of ablation therapy to antiarrhythmic drug therapy in preventing atrial fibrillation ( AF ) relapses in patients with paroxysmal or persistent AF in whom antiarrhythmic drug therapy had already failed . METHODS AND RESULTS One hundred and thirty seven patients were r and omized to ablation and antiarrhythmic drug therapy ( ablation group ) or antiarrhythmic drug therapy alone ( control group ) . In the ablation group , patients underwent cavo-tricuspid and left inferior pulmonary vein (PV)-mitral isthmus ablation plus circumferential PV ablation . The primary end-point of the study was the absence of any recurrence of atrial arrhythmia lasting > 30 s in the 1-year follow-up period , after 1-month blanking period . Three ( 4.4 % ) major complications were related to ablation : one patient had a stroke during left atrium ablation , another suffered transient phrenic paralysis , and the third had a pericardial effusion which required pericardiocentesis . After 12 months of follow-up , 63/69 ( 91.3 % ) control group patients had at least one AF recurrence , whereas 30/68 ( 44.1 % ) ( P atrial arrhythmia recurrence ( four patients had atrial flutter , 26 patients AF ) . CONCLUSION Ablation therapy combined with antiarrhythmic drug therapy is superior to antiarrhythmic drug therapy alone in preventing atrial arrhythmia recurrences in patients with paroxysmal or persistent AF in whom antiarrhythmic drug therapy has already failed", "INTRODUCTION Atrial fibrillation ( AF ) and diabetes mellitus type 2 ( DM2 ) often coexist ; however , a small number of patients with DM2 undergoing catheter ablation ( CA ) of AF have been included in previous studies . The aim of this study was to evaluate safety and efficacy of ablation therapy in DM2 patients with drug refractory AF . METHODS AND RESULTS From January 2005 to September 2006 , 70 patients with a diagnosis of DM2 and paroxysmal ( n = 29 ) or persistent ( n = 41 ) AF were r and omized to receive either pulmonary vein isolation or a new antiarrhythmic drug treatment ( ADT ) with a 1-year follow-up . The primary endpoint was the time to first AF recurrence . By Kaplan-Meier analysis , at the end of follow-up , 42.9 % of patients in the ADT group and 80 % of patients who received a single ablation procedure and were without medications were free of AF ( P = 0.001 ) . In the ablation group , a significant improvement in quality -of-life ( QoL ) scores as compared with ADT group was observed . Six patients in the ADT group ( 17.1 % ) developed significant adverse drug effects . Hospitalization rate during follow-up was higher in the ADT group ( P = 0.01 ) . The only complication attributable to ablation was one significant access-site hematoma . CONCLUSION In patients with DM2 , CA of AF provides significant clinical benefits over the ADT and appears to be a reasonable approach regarding feasibility , effectiveness , and low procedural risk", "BACKGROUND Early recurrences of atrial tachyarrhythmias ( ERAT ) are common after atrial fibrillation ( AF ) ablation , and predict late recurrences ( LR ) . We sought to determine the impact of different ablation strategies on ERAT and LR . METHODS AND RESULTS The STAR-AF trial r and omized 100 patients with paroxysmal or persistent AF to ablation of complex fractionated electrograms ( CFAE ) alone , pulmonary vein isolation ( PVI ) alone , or combined PVI + CFAE . Patients were followed for 12 months . ERAT was defined as any recurrence of AF , atrial tachycardia , or flutter ( AT/AFL ) > 30 seconds during the first 3 months of follow-up . LR was defined as any recurrence of AF/AT/AFL > 30 seconds 3 - 12 months post . Forty-nine patients experienced ERAT . The index ablation strategy was the only independent predictor of ERAT on multivariate analysis ( HR 2.24 PVI vs PVI + CFAE ; and HR 2.65 CFAE vs PVI + CFAE ) . Fifty-two patients experienced LR . The presence of ERAT ( HR 3.23 ) , the use of antiarrhythmic drug ( AAD ) in the first 3 months postablation ( HR 2.85 ) , and the index ablation strategy were independently associated with LR ( HR 3.42 PVI vs PVI + CFAE ; HR 4.72 CFAE vs PVI + CFAE ) . Thirty-five of 49 ( 71 % ) patients with ERAT and 17 ( 33 % ) of 51 patients without ERAT had LR ( P left atrium size ( HR 1.08 ) , the use of AAD in the first 3 months postablation ( HR 2.86 ) and the index ablation strategy were independently associated with LR ( HR 4.77 PVI vs PVI + CFAE ; HR 4.45 CFAE vs PVI + CFAE ) . CONCLUSION ERAT is common following AF ablation and is strongly associated with LR . Although CFAE ablation alone results in higher rates of early and LR , the addition of CFAE to PVI results in increased long-term success without an increase in ERAT", "OBJECTIVES We compared ablation strategy with antiarrhythmic drug therapy ( ADT ) in patients with paroxysmal atrial fibrillation ( PAF ) . BACKGROUND Atrial fibrillation ( AF ) ablation strategy is superior to ADT in patients with an initial history of PAF , but its role in patients with a long history of AF as compared with ADT remains a challenge . METHODS One hundred ninety-eight patients ( age , 56 + /- 10 years ) with PAF of 6 + /- 5 years ' duration ( mean AF episodes 3.4/month ) who had failed ADT were r and omized to AF ablation by circumferential pulmonary vein ablation ( CPVA ) or to the maximum tolerable doses of another ADT , which included flecainide , sotalol , and amiodarone . Crossover to CPVA was allowed after 3 months of ADT . RESULTS By Kaplan-Meier analysis , 86 % of patients in the CPVA group and 22 % of those in the ADT group who did not require a second ADT were free from recurrent atrial tachyarrhythmias ( AT ) ( p CPVA and ADT groups , respectively , were AT-free . Ejection fraction , hypertension , and age independently predicted AF recurrences in the ADT group . Circumferential pulmonary vein ablation was associated with fewer cardiovascular hospitalizations ( p transient ischemic attack and 1 pericardial effusion occurred in the CPVA group ; side effects of ADT were observed in 23 patients . CONCLUSIONS Circumferential pulmonary vein ablation is more successful than ADT for prevention of PAF with few complications . Atrial fibrillation ablation warrants consideration in selected patients in whom ADT had already failed and maintenance of sinus rhythm is desired . ( A Controlled R and omized Trial of CPVA Versus Antiarrhythmic Drug Therapy in for Paroxysmal AF : APAF/01 ; http:// clinical trials.gov/ct/show ; NCT00340314 )", "OBJECTIVES The purpose of this study was to determine quality of life ( QOL ) and exercise performance ( EP ) in patients with persistent atrial fibrillation ( AF ) converted to sinus rhythm ( SR ) compared with those remaining in or reverting to AF . BACKGROUND Restoration of SR in patients with AF improving QOL and EP remains controversial . METHODS Patients with persistent AF were r and omized double-blind to amiodarone , sotalol , or placebo . Those not achieving SR at day 28 were cardioverted and classified into SR or AF groups at 8 weeks ( n = 624 ) and 1 year ( n = 556 ) . The QOL ( SF-36 ) , symptom checklist ( SCL ) , specific activity scale ( SAS ) , AF severity scale ( AFSS ) , and EP were assessed . RESULTS Favorable changes were seen in SR patients at 8 weeks in physical functioning ( p physical role limitations ( p = 0.03 ) , general health ( p = 0.002 ) , and vitality ( p general health ( p = 0.007 ) and social functioning ( p = 0.02 ) . Changes in the scores for SCL severity ( p = 0.01 ) , functional capacity ( p = 0.003 ) , and AFSS symptom burden ( p SCL severity ( p AF symptom burden ( p EP in SR versus AF was greater from baseline to 8 weeks ( p = 0.01 ) and to 1 year ( p = 0.02 ) . The EP correlated with physical functioning and functional capacity except in the AF group at 1 year . CONCLUSIONS In patients with persistent AF , restoration and maintenance of SR was associated with improvements in QOL measures and EP . There was a strong correlation between QOL measures and EP", "IMPORTANCE Atrial fibrillation ( AF ) is the most common rhythm disorder seen in clinical practice . Antiarrhythmic drugs are effective for reduction of recurrence in patients with symptomatic paroxysmal AF . Radiofrequency ablation is an accepted therapy in patients for whom antiarrhythmic drugs have failed ; however , its role as a first-line therapy needs further investigation . OBJECTIVE To compare radiofrequency ablation with antiarrhythmic drugs ( st and ard therapy ) in treating patients with paroxysmal AF as a first-line therapy . DESIGN , SETTING , AND PATIENTS A r and omized clinical trial involving 127 treatment-naive patients with paroxysmal AF were r and omized at 16 centers in Europe and North America to received either antiarrhythmic therapy or ablation . The first patient was enrolled July 27 , 2006 ; the last patient , January 29 , 2010 . The last follow-up was February 16 , 2012 . INTERVENTIONS Sixty-one patients in the antiarrhythmic drug group and 66 in the radiofrequency ablation group were followed up for 24 months . MAIN OUTCOMES AND MEASURES The time to the first documented atrial tachyarrhythmia of more than 30 seconds ( symptomatic or asymptomatic AF , atrial flutter , or atrial tachycardia ) , detected by either scheduled or unscheduled electrocardiogram , Holter , transtelephonic monitor , or rhythm strip , was the primary outcome . Secondary outcomes included symptomatic recurrences of atrial tachyarrhythmias and quality of life measures assessed by the EQ-5D tool . RESULTS Forty-four patients ( 72.1 % ) in the antiarrhythmic group and in 36 patients ( 54.5 % ) in the ablation group experienced the primary efficacy outcome ( hazard ratio [ HR ] , 0.56 [ 95 % CI , 0.35 - 0.90 ] ; P = .02 ) . For the secondary outcomes , 59 % in the drug group and 47 % in the ablation group experienced the first recurrence of symptomatic AF , atrial flutter , atrial tachycardia ( HR , 0.56 [ 95 % CI , 0.33 - 0.95 ] ; P = .03 ) . No deaths or strokes were reported in either group ; 4 cases of cardiac tamponade were reported in the ablation group . In the st and ard treatment group , 26 patients ( 43 % ) underwent ablation after 1-year . Quality of life was moderately impaired at baseline in both groups and improved at the 1 year follow-up . However , improvement was not significantly different among groups . CONCLUSIONS AND RELEVANCE Among patients with paroxysmal AF without previous antiarrhythmic drug treatment , radiofrequency ablation compared with antiarrhythmic drugs result ed in a lower rate of recurrent atrial tachyarrhythmias at 2 years . However , recurrence was frequent in both groups . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00392054", "OBJECTIVES We sought to assess the impact of intermittent atrial fibrillation ( AF ) on health-related quality of life ( QoL ) . BACKGROUND Intermittent AF is a common condition with little data on health-related QoL question naires to guide investigational therapies . METHODS Out patients from four centers , with documented AF ( n = 152 ) , completed vali date d QoL question naires ( Medical Outcomes Study Short Form 36 [ SF-36 ] , Specific Activity , Symptom Checklist , Illness Intrusiveness and University of Toronto AF Severity Scales ) . Comparison groups were made up of healthy individuals ( n = 47 ) and four cardiac control groups : published ( n = 78 ) and created for study ( n = 69 ) percutaneous transluminal coronary angioplasty ( PTCA ) ; published heart failure ( n = 216 ) and published postmyocardial infa rct ion ( MI ) ( n = 107 ) . RESULTS Across all domains of the SF-36 , AF patients reported substantially worse QoL than healthy controls ( 1.3 to 2.0 st and ard deviation units ) , with scores of 24 % , 23 % , 16 % and 30 % lower than healthy individuals on measures of physical and social functioning , mental and general health , respectively ( all p domains of the SF-36 and the same as heart failure controls on SF-36 psychological subscales . Patients with AF were as impaired or worse than study PTCA controls on measures of illness intrusiveness , activity limitations and symptoms . Associations between objective disease indexes and subjective QoL measures had poor correlations and accounted for Quality of life is as impaired in patients with intermittent AF as in patients with significant structural heart disease . Patients ' perception of QoL is not dependent on the objective measures of disease severity that are usually employed", "OBJECTIVES This study sought to compare catheter ablation with rate control for persistent atrial fibrillation ( AF ) in heart failure ( HF ) . BACKGROUND The optimal therapy for AF in HF is unclear . Drug-based rhythm control has not proved clinical ly beneficial . Catheter ablation improves cardiac function in patients with HF , but impact on physiological performance has not been formally evaluated in a r and omized trial . METHODS In a r and omized , open-label , blinded-endpoint clinical trial , adults with symptomatic HF , radionuclide left ventricular ejection fraction ( EF ) ≤35 % , and persistent AF were assigned to undergo catheter ablation or rate control . Primary outcome was 12-month change in peak oxygen consumption . Secondary endpoints were quality of life , B-type natriuretic peptide , 6-min walk distance , and EF . Results were analyzed by intention-to-treat . RESULTS Fifty-two patients ( age 63 ± 9 years , EF 24 ± 8 % ) were r and omized , 26 each to ablation and rate control . At 12 months , 88 % of ablation patients maintained sinus rhythm ( single-procedure success 68 % ) . Under rate control , rate criteria were achieved in 96 % . The primary endpoint , peak oxygen consumption , significantly increased in the ablation arm compared with rate control ( difference + 3.07 ml/kg/min , 95 % confidence interval : 0.56 to 5.59 , p = 0.018 ) . The change was not evident at 3 months ( + 0.79 ml/kg/min , 95 % confidence interval : -1.01 to 2.60 , p = 0.38 ) . Ablation improved Minnesota score ( p = 0.019 ) and B-type natriuretic peptide ( p = 0.045 ) and showed nonsignificant trends toward improved 6-min walk distance ( p = 0.095 ) and EF ( p = 0.055 ) . CONCLUSIONS This first r and omized trial of ablation versus rate control to focus on objective exercise performance in AF and HF shows significant benefit from ablation , a strategy that also improves symptoms and neurohormonal status . The effects develop over 12 months , consistent with progressive amelioration of the HF syndrome . ( A R and omised Trial to Assess Catheter Ablation Versus Rate Control in the Management of Persistent Atrial Fibrillation in Chronic Heart Failure ; NCT00878384 )", "BACKGROUND There are two approaches to the treatment of atrial fibrillation : one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm , and the other is the use of rate-controlling drugs , allowing atrial fibrillation to persist . In both approaches , the use of anticoagulant drugs is recommended . METHODS We conducted a r and omized , multicenter comparison of these two treatment strategies in patients with atrial fibrillation and a high risk of stroke or death . The primary end point was overall mortality . RESULTS A total of 4060 patients ( mean [ + /-SD ] age , 69.7+/-9.0 years ) were enrolled in the study ; 70.8 percent had a history of hypertension , and 38.2 percent had coronary artery disease . Of the 3311 patients with echocardiograms , the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percent . There were 356 deaths among the patients assigned to rhythm-control therapy and 310 deaths among those assigned to rate-control therapy ( mortality at five years , 23.8 percent and 21.3 percent , respectively ; hazard ratio , 1.15 [ 95 percent confidence interval , 0.99 to 1.34 ] ; P=0.08 ) . More patients in the rhythm-control group than in the rate-control group were hospitalized , and there were more adverse drug effects in the rhythm-control group as well . In both groups , the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio was subtherapeutic . CONCLUSIONS Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy , and there are potential advantages , such as a lower risk of adverse drug effects , with the rate-control strategy . Anticoagulation should be continued in this group of high-risk patients", "BACKGROUND Catheter ablation is less successful for persistent atrial fibrillation than for paroxysmal atrial fibrillation . Guidelines suggest that adjuvant substrate modification in addition to pulmonary-vein isolation is required in persistent atrial fibrillation . METHODS We r and omly assigned 589 patients with persistent atrial fibrillation in a 1:4:4 ratio to ablation with pulmonary-vein isolation alone ( 67 patients ) , pulmonary-vein isolation plus ablation of electrograms showing complex fractionated activity ( 263 patients ) , or pulmonary-vein isolation plus additional linear ablation across the left atrial roof and mitral valve isthmus ( 259 patients ) . The duration of follow-up was 18 months . The primary end point was freedom from any documented recurrence of atrial fibrillation lasting longer than 30 seconds after a single ablation procedure . RESULTS Procedure time was significantly shorter for pulmonary-vein isolation alone than for the other two procedures ( P pulmonary-vein isolation alone were free from recurrent atrial fibrillation , as compared with 49 % of patients assigned to pulmonary-vein isolation plus complex electrogram ablation and 46 % of patients assigned to pulmonary-vein isolation plus linear ablation ( P=0.15 ) . There were also no significant differences among the three groups for the secondary end points , including freedom from atrial fibrillation after two ablation procedures and freedom from any atrial arrhythmia . Complications included tamponade ( three patients ) , stroke or transient ischemic attack ( three patients ) , and atrioesophageal fistula ( one patient ) . CONCLUSIONS Among patients with persistent atrial fibrillation , we found no reduction in the rate of recurrent atrial fibrillation when either linear ablation or ablation of complex fractionated electrograms was performed in addition to pulmonary-vein isolation . ( Funded by St. Jude Medical ; Clinical Trials.gov number , NCT01203748 . )", "The limited efficacy and proarrhythmic risks of antiarrhythmia agents have result ed in alternative therapeutic approaches . Radiofrequency ablation has been reported to be an effective treatment of patients with atrial fibrillation . However , there is no r and omized clinical trial comparing drug and radiofrequency ablation . The authors r and omized 30 patients with chronic atrial fibrillation refractory to medication into amiodarone and radiofrequency ablation . The primary objective of this study was to compare the efficacy of amiodarone and radiofrequency ablation in the maintenance of sinus rhythm at 1 year after r and omization . Pulmonary vein isolation and linear ablation of right atrium was the technique used for radiofrequency ablation . There were no significant differences in baseline patient characteristics between the 2 groups . The results of this study showed that the probability of free from atrial fibrillation was better in the radiofrequency ablation group compared to amiodarone ( 78.6 % in the ablation group and 40 % in the amiodarone group , p = 0.018 ) . Radiofrequency ablation results in a significant reduction in symptoms relating to atrial fibrillation and a significant improvement in quality of life , whereas amiodarone had no significant effect on symptoms and quality of life . There was an ischemic stroke as a major complication related to radiofrequency ablation . Amiodarone was associated with adverse effects in 46.7 per cent of patients and needed discontinuation in 1 patient . In conclusion , radiofrequency ablation is an effective alternative treatment in patients with atrial fibrillation refractory to medication", "Background and objective Little is known about the outcome of catheter ablation of atrial fibrillation ( AF ) in patients with diabetes mellitus ( DM ) . We investigated the safety and efficacy of catheter ablation of AF in patients with DM . Material s and methods Thirty one patients with DM from a group of 263 consecutive patients undergoing a first-time catheter ablation of AF procedure were enrolled in a prospect i ve study . The ablation protocol ( guided by CARTO system ) consisted in two continuous circular lesions around ipsilateral pulmonary veins . Results The following clinical characteristics differed between DM and no-DM patients : age ( 62.0 ± 10.8 vs. 56.1 ± 10.6 years , P = 0.004 ) , longer AF history ( 9.6 ± 9.3 vs. 6.7 ± 6.3 years , P = 0.024 ) , significantly larger left atrium size ( 41.1 ± 7.8 vs. 38.3 ± 5.8 mm , P = 0.021 ) , hypertension ( 58.1 vs. 35.8 % , P = 0.018 ) and structural heart disease ( 67.7 vs. 43.5 % , P = 0.011 ) . Despite a similar AF recurrence rate in DM and no-DM patients ( 32.3 vs. 22.4 % , P = 0.240 ) , the ablation procedure was complicated in 28 patients ( 11 hematomas , three cardiac tamponades and three strokes ) and the incidence of complications was significantly higher in DM than in no-DM patients ( 29.0 vs. 8.2 % , respectively , P = 0.002 ) . Multivariate analysis showed that DM was an independent risk factor for complications occurrence ( odd ratio 5.936 , 95 % confidence interval 2.059 to 17.112 , P = 0.001 ) . Conclusions First catheter ablation of AF procedure in DM patients was equally efficacious than in no-DM patients . However , DM patients had a higher incidence of complications , mostly thrombotic or hemorrhagic", "BACKGROUND There are limited data comparing radiofrequency catheter ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation . METHODS We r and omly assigned 294 patients with paroxysmal atrial fibrillation and no history of antiarrhythmic drug use to an initial treatment strategy of either radiofrequency catheter ablation ( 146 patients ) or therapy with class IC or class III antiarrhythmic agents ( 148 patients ) . Follow-up included 7-day Holter-monitor recording at 3 , 6 , 12 , 18 , and 24 months . Primary end points were the cumulative and per-visit burden of atrial fibrillation ( i.e. , percentage of time in atrial fibrillation on Holter-monitor recordings ) . Analyses were performed on an intention-to-treat basis . RESULTS There was no significant difference between the ablation and drug-therapy groups in the cumulative burden of atrial fibrillation ( 90th percentile of arrhythmia burden , 13 % and 19 % , respectively ; P=0.10 ) or the burden at 3 , 6 , 12 , or 18 months . At 24 months , the burden of atrial fibrillation was significantly lower in the ablation group than in the drug-therapy group ( 90th percentile , 9 % vs. 18 % ; P=0.007 ) , and more patients in the ablation group were free from any atrial fibrillation ( 85 % vs. 71 % , P=0.004 ) and from symptomatic atrial fibrillation ( 93 % vs. 84 % , P=0.01 ) . One death in the ablation group was due to a procedure-related stroke ; there were three cases of cardiac tamponade in the ablation group . In the drug-therapy group , 54 patients ( 36 % ) underwent supplementary ablation . CONCLUSIONS In comparing radiofrequency ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation , we found no significant difference between the treatment groups in the cumulative burden of atrial fibrillation over a period of 2 years . ( Funded by the Danish Heart Foundation and others ; MANTRA-PAF Clinical Trials.gov number , NCT00133211 . )", "CONTEXT Antiarrhythmic drugs are commonly used for prevention of recurrent atrial fibrillation ( AF ) despite inconsistent efficacy and frequent adverse effects . Catheter ablation has been proposed as an alternative treatment for paroxysmal AF . OBJECTIVE To determine the efficacy of catheter ablation compared with antiarrhythmic drug therapy ( ADT ) in treating symptomatic paroxysmal AF . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve , multicenter , r and omized ( 2:1 ) , unblinded , Bayesian- design ed study conducted at 19 hospitals of 167 patients who did not respond to at least 1 antiarrhythmic drug and who experienced at least 3 AF episodes within 6 months before r and omization . Enrollment occurred between October 25 , 2004 , and October 11 , 2007 , with the last follow-up on January 19 , 2009 . INTERVENTION Catheter ablation ( n = 106 ) or ADT ( n = 61 ) , with assessment for effectiveness in a comparable 9-month follow-up period . MAIN OUTCOME MEASURES Time to protocol -defined treatment failure . The proportion of patients who experienced major treatment-related adverse events within 30 days of catheter ablation or ADT was also reported . RESULTS At the end of the 9-month effectiveness evaluation period , 66 % of patients in the catheter ablation group remained free from protocol -defined treatment failure compared with 16 % of patients treated with ADT . The hazard ratio of catheter ablation to ADT was 0.30 ( 95 % confidence interval , 0.19 - 0.47 ; P 30-day treatment-related adverse events occurred in 5 of 57 patients ( 8.8 % ) treated with ADT and 5 of 103 patients ( 4.9 % ) treated with catheter ablation . Mean quality of life scores improved significantly in patients treated by catheter ablation compared with ADT at 3 months ; improvement was maintained during the course of the study . CONCLUSION Among patients with paroxysmal AF who had not responded to at least 1 antiarrhythmic drug , the use of catheter ablation compared with ADT result ed in a longer time to treatment failure during the 9-month follow-up period . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00116428" ]	4118979e-06ff-11f0-808a-c43d1ab1c353
Background Low physical activity has been identified as a major risk factor for cardiovascular disease . Medical societies therefore recommend increased physical activity be part of any antihypertensive therapy . Objective Focusing on patient-relevant outcomes such as mortality and cardiovascular events , this review was conducted to assess the long-term effects of interventions aim ing at increasing physical activity in comparison with no such interventions on adult patients with essential hypertension . Data sources We search ed for high- quality systematic review s in MEDLINE , EMBASE , Cochrane Data base of Systematic Review s ( Cochrane Review s ) , Data base of Abstract s of Review s of Effects ( Other Review s ) and Health Technology Assessment Data base ( Technology Assessment s ) published between 1997 and February 2009 and for r and omized controlled trials ( RCTs ) in MEDLINE , EMBASE and Cochrane Central Register of Controlled Trials ( Clinical Trials ) published before September 2012 . Additional studies were identified by h and search ing reference lists of review s. Study selection RCTs with at least 24 weeks ’ follow-up that evaluated the effect of increased physical activity on the blood pressure of adults with essential hypertension were included in our review . Primary outcomes were all-cause mortality , cardiovascular morbidity and mortality , end-stage renal disease , quality of life and adverse events . Study appraisal and synthesis methods When appropriate , we used r and om effects meta-analyses to determine mean difference with 95 % confidence intervals for each endpoint . All data were analysed using the Review Manager software version 5.0.24 from the Cochrane Collaboration . Results None of the included nine trials , covering 891 patients with hypertension , provided sufficient data on patient-relevant outcomes such as mortality , cardiovascular events or injuries related to physical activity . Information on changes in systolic and diastolic blood pressure was provided for all included trials . The majority of the included RCTs reported that increased physical activity led to a decrease in systolic and diastolic blood pressure of 5–10 and 1–6 mmHg , respectively , but due to marked heterogeneity in the meta-analyses both for systolic and diastolic blood pressure ( I2 = 70.0 and 73.0 % ) , no effect estimates were provided . Limitations About 50 % of the included trials were small , evaluating at most 20 participants per study group , and more than twothirds were deemed to have a high risk of bias . Conclusions Although a decrease in blood pressure is shown to be a consequence of increased physical activity , RCTs of appropriate study size and quality that examine potential patient-relevant benefits or harms still need to be conducted to evaluate whether physical activity really improves the health of patients with essential hypertension	[ "The Oslo Diet and Exercise Study ( ODES ) is an unmasked r and omized 2 x 2 factorial trial of 1-year duration for each participant . During 1990 - 1991 219 participants ( 198 males and 21 females ) aged 41 - 50 were r and omized into one of four treatment groups ; no treatment ( control ) , dietary changes alone , exercise alone , or a combination of the two treatments . At inclusion , the participants had no overt heart disease , but they had increased body weight ; slightly increased blood pressure , serum triglycerides , and total cholesterol , and they had decreased HDL cholesterol . Further , they were all inactive at leisure time . The primary aim of the trial is to compare the isolated and combined effects of the four treatments on the variables fibrinogen , fibrinolytic capacity , coagulation factor VII , and platelet volume . A series of secondary hypotheses will also be tested , such as the effects on other coagulation and fibrinolytic components and activities ; lipids and lipoproteins ; fatty acids ; glucose and insulin response to a glucose load ; clinical , physiological , and anthropometric variables ; and quality of life . The dietary treatments are adapted according to each participant 's risk profile ( level of total cholesterol , HDL cholesterol , triglycerides , blood pressure , and body weight ) . Fish and fish products are recommended . Special emphasis is put on caloric restriction in those who are overweight and those with elevated blood pressure . Exercise sessions take place three times a week under the guidance of highly qualified instructors . The aim is to increase peak oxygen uptake through aerobic endurance training . Adherence to the exercise program is monitored closely", "Are there ethnic differences in the pathogenesis of hypertension and are these sufficient to influence choice of treatment ? I will also consider prevalence and complications . Because hypertension is the biggest and an almost entirely treatable cause of cardiovascular disease , even small ethnic differences in its optimum management have large implication s for health re sources . Ethnic differences in the type of hypertension give us the strongest evidence that we have for the concept that hypertension exists in two broad types . As for diabetes , hypertension can usefully be considered as of type 1 or type 2 , each with its own preferred treatment . Results of recent trials support this view and emphasise the importance of choosing the right strategy for the type of hypertension to be treated . Numerous published studies , including many review s , compare one or more of the four parameters to be discussed in different ethnic groups . A few have prospect ively identified similar numbers in the ethnic groups being compared or a minimum proportion of the ethnic minority . But most are retrospective analyses of studies in which a multi-ethnic population was recruited . I found relevant studies with Medline and Google-Scholar , search ing for “ hypertension ” with either “ ethnic ” or the names of individual ethnic groups . White and black people are the key ethnic groups to have been compared . Some prevalence studies included Asians , but these studies give insufficient information on which to make reliable statements about pathogenesis or treatment . Progress in underst and ing the pathogenesis of hypertension has been slow because essential hypertension is extremely complex at a molecular level.1 Conversely , hypertension exists in only two broad physiological types . This has been long predictable in theory from Poiseuille 's law ( that blood pressure is the product of vasoconstriction and volume ) and supported in practice from the observation that a few of the syndromes where hypertension is", "OBJECTIVES To determine whether the encouragement of walking an extra 30 minutes a day decreases blood pressure in adult African Americans with newly diagnosed hypertension . DESIGN R and omized controlled study . PARTICIPANTS AND SETTING A total of 19 African American adults with newly diagnosed hypertension from an urban family medicine office were r and omly assigned to intervention and control groups . INTERVENTION The intervention group was advised to walk an extra 30 minutes per day . The control group was not given this advice . All subjects used pedometers to record the number of daily steps . MAIN OUTCOME MEASURE Change in systolic and diastolic blood pressure in the intervention and control groups after six months of trial , controlling for age and body mass index . RESULTS At the end of six months , a mixed analysis of covariance did not reveal a significant group-by-time interaction for systolic blood pressure . However , positive effects of walking were evidence d ; adjusted mean systolic blood pressure dropped by 9.0 % for those in the intervention group and 2.33 % for those in the control group . Similarly , adjusted mean diastolic pressure dropped by 7.42 % for the intervention group and remained essentially unchanged for the control group ( P = .08 ) CONCLUSIONS : The findings of this study indicate that walking an extra 30 minutes a day is associated with lower mean blood pressure among adult African Americans with newly diagnosed hypertension", "BACKGROUND Blood pressure reduction achieved with beta-blockers and diuretics is the best recorded intervention to date for prevention of cardiovascular morbidity and death in patients with hypertension . Left ventricular hypertrophy ( LVH ) is a strong independent indicator of risk of cardiovascular morbidity and death . We aim ed to establish whether selective blocking of angiotensin II improves LVH beyond reducing blood pressure and , consequently , reduces cardiovascular morbidity and death . METHODS We did a double-masked , r and omised , parallel-group trial in 9193 participants aged 55 - 80 years with essential hypertension ( sitting blood pressure 160 - 200/95 - 115 mm Hg ) and LVH ascertained by electrocardiography ( ECG ) . We assigned participants once daily losartan-based or atenolol-based antihypertensive treatment for at least 4 years and until 1040 patients had a primary cardiovascular event ( death , myocardial infa rct ion , or stroke ) . We used Cox regression analysis to compare regimens . FINDINGS Blood pressure fell by 30.2/16.6 ( SD 18.5/10.1 ) and 29.1/16.8 mm Hg ( 19.2/10.1 ) in the losartan and atenolol groups , respectively . The primary composite endpoint occurred in 508 losartan ( 23.8 per 1000 patient-years ) and 588 atenolol patients ( 27.9 per 1000 patient-years ; relative risk 0.87 , 95 % CI 0.77 - 0.98 , p=0.021 ) . 204 losartan and 234 atenolol patients died from cardiovascular disease ( 0.89 , 0.73 - 1.07 , p=0.206 ) ; 232 and 309 , respectively , had fatal or non-fatal stroke ( 0.75 , 0.63 - 0.89 , p=0.001 ) ; and myocardial infa rct ion ( non-fatal and fatal ) occurred in 198 and 188 , respectively ( 1.07 , 0.88 - 1.31 , p=0.491 ) . New-onset diabetes was less frequent with losartan . Interpretation Losartan prevents more cardiovascular morbidity and death than atenolol for a similar reduction in blood pressure and is better tolerated . Losartan seems to confer benefits beyond reduction in blood pressure", "OBJECTIVES The success of any clinical trial depends strongly on recruiting enough participants in a reasonable time period . This paper aims to identify the obstacles , as well as the successful aspects , of recruiting of older participants into an exercise study . DESIGN This describes the recruitment of 299 older adults into a r and omized , controlled trial of exercise advice in a general practice setting . Letters of invitation were sent from two general practice s inviting the patients to attend a 15-minute screening appointment . Patients considered eligible for enrollment were then scheduled for a baseline appointment and r and omized into the trial . SETTING Two general practice s in Adelaide , South Australia . PARTICIPANTS Healthy , sedentary , community-dwelling patients aged 60 years or older . RESULTS A total of 2878 letters of invitation were sent , and 913 patients attended a screening appointment . Of these , 351 ( 38.4 % ) were initially eligible , with one-third excluded because they were already too physically active . Two hundred ninety-nine participants , approximately 1 of every 10 patients sent letters , were enrolled in the project at the end of a 15-week period . DISCUSSION A general practice approach was effective in recruiting 299 older adults to an exercise project within an acceptable time frame . Factors promoting the success of recruitment through general practice included choosing large , well established practice s , computerized age-sex registers , and placing minimal dem and s on the general practitioners and practice staff . A continuing problem with recruiting participants for a project involving exercise is that the volunteer population tends to be healthy and interested in physical activity", "Autonomic neuropathy in diabetes leads to impaired regulation of blood pressure and heart rate variability ( HRV ) , which is due to a shift in cardiac autonomic balance towards sympathetic dominance . Lower HRV has been considered a predictor of cardiac mortality and morbidity . Deep breathing test is a simple method to measure HRV and it provides a sensitive measure of cardiac autonomic function . The effect of long-term physical activity on HRV in type-2 diabetes mellitus is inconclusive . We aim ed to evaluate the effects of regular physical exercise on HRV with deep breathing in type 2 diabetes ( n = 105 ) . Thirty normotensive diabetic patients and 25 hypertensive diabetic patients underwent physical exercise program for 12 months , and the other 50 patients ( 22 normotensive and 28 hypertensive diabetic patients ) were considered the non-exercised group . Electrocardiogram was recorded during deep breathing and HRV was measured . Regular exercise significantly increased HRV in diabetic patients with and without hypertension . The degree of the increase in HRV was greater in hypertensive diabetic patients ( p exercise , glycosylated hemoglobin levels were decreased in both groups of diabetic patients . Moreover , the hypertensive diabetic patients showed a decrease ( p blood pressure after regular exercise . Thus , regular exercise training increases HRV , suggesting that there is a shift in the cardiac sympathovagal balance in favor of parasympathetic dominance in diabetic patients . Long-term physical training may be an effective means to reverse the autonomic dysregulation seen in type 2 diabetes", "AIM To determine the effect on blood pressure from brisk walking with or without salt restriction in a community based sample of treated hypertensives . METHODS The intervention was undertaken in a community setting with a factorial r and omised controlled trial and blinded assessment of blood pressure . One hundred and eighty one healthy adult volunteers with a sedentary lifestyle and on pharmacological therapy for hypertension briskly walked for 40 minutes three times per week with or without salt restriction . Systolic and diastolic blood pressure were assessed at three and six months . RESULTS Of the original 208 participants 181 ( 87 % ) completed the study . significant reductions of up to 7 mm Hg were found in systolic blood pressure at 3 months for brisk walking alone ( p = 0.04 ) and salt restriction alone ( p = 0.03 ) but not for the combined intervention ( p = 0.17 ) . No significant change was found for diastolic blood pressure . There was no significant change in blood pressure at 6 months . CONCLUSIONS Simple advice on exercise and sodium restriction in a community setting can significantly lower systolic blood pressure at least for 3 months . The combination of the two interventions was less effective than each therapy alone", "This study determined the effects of endurance or resistance exercise training on maximal O2 consumption ( VO2max ) and the cardiovascular responses to exercise of 70- to 79-yr-old men and women . Healthy untrained subjects were r and omly assigned to a control group ( n = 12 ) or to an endurance ( n = 16 ) or resistance training group ( n = 19 ) . Training consisted of three sessions per week for 26 wk . Resistance training consisted of one set of 8 - 12 repetitions on 10 Nautilus machines . Endurance training consisted of 40 min at 50 - 70 % VO2max and at 75 - 85 % VO2max for the first and last 13 wk of training , respectively . The endurance training group increased its VO2max by 16 % during the first 13 wk of training and by a total of 22 % after 26 wk of training ; this group also increased its maximal O2 pulse , systolic blood pressure , and ventilation , and decreased its heart rate and perceived exertion during submaximal exercise . The resistance training group did not elicit significant changes in VO2max or in other maximal or submaximal cardiovascular responses despite eliciting 9 and 18 % increases in lower and upper body strength , respectively . Thus healthy men and women in their 70s can respond to prolonged endurance exercise training with adaptations similar to those of younger individuals . Resistance training in older individuals has no effect on cardiovascular responses to submaximal or maximal treadmill exercise", "CONTEXT Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality , but the optimal first-step therapy is unknown . OBJECTIVE To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease ( CHD ) or other cardiovascular disease ( CVD ) events vs treatment with a diuretic . DESIGN The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) , a r and omized , double-blind , active-controlled clinical trial conducted from February 1994 through March 2002 . SETTING AND PARTICIPANTS A total of 33 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers . INTERVENTIONS Participants were r and omly assigned to receive chlorthalidone , 12.5 to 25 mg/d ( n = 15 255 ) ; amlodipine , 2.5 to 10 mg/d ( n = 9048 ) ; or lisinopril , 10 to 40 mg/d ( n = 9054 ) for planned follow-up of approximately 4 to 8 years . MAIN OUTCOME MEASURES The primary outcome was combined fatal CHD or nonfatal myocardial infa rct ion , analyzed by intent-to-treat . Secondary outcomes were all-cause mortality , stroke , combined CHD ( primary outcome , coronary revascularization , or angina with hospitalization ) , and combined CVD ( combined CHD , stroke , treated angina without hospitalization , heart failure [ HF ] , and peripheral arterial disease ) . RESULTS Mean follow-up was 4.9 years . The primary outcome occurred in 2956 participants , with no difference between treatments . Compared with chlorthalidone ( 6-year rate , 11.5 % ) , the relative risks ( RRs ) were 0.98 ( 95 % CI , 0.90 - 1.07 ) for amlodipine ( 6-year rate , 11.3 % ) and 0.99 ( 95 % CI , 0.91 - 1.08 ) for lisinopril ( 6-year rate , 11.4 % ) . Likewise , all-cause mortality did not differ between groups . Five-year systolic blood pressures were significantly higher in the amlodipine ( 0.8 mm Hg , P = .03 ) and lisinopril ( 2 mm Hg , P chlorthalidone , and 5-year diastolic blood pressure was significantly lower with amlodipine ( 0.8 mm Hg , P amlodipine vs chlorthalidone , secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine ( 10.2 % vs 7.7 % ; RR , 1.38 ; 95 % CI , 1.25 - 1.52 ) . For lisinopril vs chlorthalidone , lisinopril had higher 6-year rates of combined CVD ( 33.3 % vs 30.9 % ; RR , 1.10 ; 95 % CI , 1.05 - 1.16 ) ; stroke ( 6.3 % vs 5.6 % ; RR , 1.15 ; 95 % CI , 1.02 - 1.30 ) ; and HF ( 8.7 % vs 7.7 % ; RR , 1.19 ; 95 % CI , 1.07 - 1.31 ) . CONCLUSION Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive . They should be preferred for first-step antihypertensive therapy", "The purpose of this study was to investigate the effect of 1-year diet intervention , exercise intervention and both combined on blood pressure ( BP ) in normotensives and mild hypertensives . Two hundred and nineteen sedentary middle aged men and women with slightly deranged coronary heart disease ( CHD ) risk factors were r and omised to a control , a diet , an exercise and a diet + exercise group . Based on baseline diastolic BP , participants were divided into tertiles , giving baseline average BP of 141.4/96.7 in tertile 1 , 130.7/87.6 in tertile 2 and 121.9/79.0 in tertile 3 . The 1-year net-difference in BP between the intervention groups and the control group decreased across the tertiles ; in tertile 1 being -11.2/-6.7 ( p systolic BP only ) and -7.0/-5.1 ( NS ) in the combined , diet and exercise group respectively . Triglycerides , HDL cholesterol , and insulin variables were significantly and favourably changed , the changes being most marked in the combined group . The results show that diet and diet + exercise are about equally effective in reducing BP , and the effects may be dependent on the baseline level . Within the upper tertile of baseline BP , the decline in BP in the combined intervention and the diet group are almost comparable to those obtained with drug treatment . In addition , other important CHD risk factors were all changed in a beneficial direction", "OBJECTIVE - To examine the prevalence , incidence , predisposing factors for hypertension , its hazards as an ingredient of the cardiovascular risk profile , and the implication s of this information for prevention and treatment . METHODS - Prospect i ve longitudinal analysis of 36-year follow-up data from the Framingham Study of the relation of antecedent blood pressure to occurrence of subsequent cardiovascular morbidity and mortality depending on the metabolically linked burden of associated risk factors . RESULTS - Hypertension is one of the most prevalent and powerful contributors to cardiovascular diseases , the leading cause of death in the United States . There is , on average , a 20 mm Hg systolic and 10 mm Hg diastolic increment increase in blood pressure from age 30 to 65 years . Isolated systolic hypertension is the dominant variety . There is no evidence of a decline in the prevalence of hypertension over 4 decades despite improvements in its detection and treatment . Hypertension contributes to all of the major atherosclerotic cardiovascular disease outcomes increasing risk , on average , 2- to 3-fold . Coronary disease , the most lethal and common sequela , deserves highest priority . Hypertension clusters with dyslipidemia , insulin resistance , glucose intolerance , and obesity , occurring in isolation in less than 20 % . The hazard depends on the number of these associated metabolically linked risk factors present . Coexistent overt cardiovascular disease also influences the hazard and choice of therapy . CONCLUSION - The absence of a decline in the prevalence of hypertension indicates an urgent need for primary prevention by weight control , exercise , and reduced salt and alcohol intake . The urgency and choice of therapy of existing hypertension should be based on the multivariate cardiovascular risk profile that more appropriately targets hypertensive persons for treatment and prevention of cardiovascular sequelae", "OBJECTIVE To study the effect of a community-based walking intervention on blood pressure among older people . METHOD The study design was a r and omized controlled trial conducted in a rural area of Taiwan between October 2002 and June 2003 . A total of 202 participants aged 60 years and over with mild to moderate hypertension was recruited . Participants r and omized to the intervention group ( n=102 ) received a six-month community-based walking intervention based on self-efficacy theory . A public health nurse provided both face-to-face and telephone support design ed to assist participants to increase their walking . Control group participants ( n=100 ) received usual primary health care . Primary outcome was change in systolic blood pressure and secondary outcomes were exercise self-efficacy , self-reported walking and diastolic blood pressure . RESULTS At six-month follow-up the mean change in systolic blood pressure was a decrease of 15.4 mmHg and 8.4 mmHg in the intervention and control group , respectively . The difference in mean change between the two groups was -7.0 mmHg ( 95 % CI , -11.5 to -2.5 mmHg , p=0.002 ) . Improvement in exercise self-efficacy scores was greater among intervention group participants ( mean difference 1.23 , 95 % CI , 0.5 to 2.0 , p=0.001 ) . Intervention group participants were more likely to report walking more ( p diastolic blood pressure ( p=0.19 ) . CONCLUSIONS Among hypertensive older people , a six-month community-based walking intervention was effective in increasing their exercise self-efficacy and reducing systolic blood pressure", "OBJECTIVE To determine whether provision of individualised physical activity advice by an exercise specialist in general practice is effective in modifying physical activity and cardiovascular risk factors in older adults . DESIGN R and omised controlled trial of individualised physical activity advice , reinforced at three and six months ( intervention ) versus no advice ( control ) . SETTING Two general practice s in Adelaide , South Australia , 1996 . PARTICIPANTS 299 adults aged 60 years or more who were healthy , sedentary and living in the community . MAIN OUTCOME MEASURES Changes to physical activity ( frequency and duration of walking and vigorous exercise ) , selected cardiovascular risk factors ( blood pressure , body weight , serum lipid levels ) and quality of life over 12 months . RESULTS Self-reported physical activity increased over the 12 months in both groups ( P time spent walking ( P intention to exercise ( P Serum levels of total and low-density lipoprotein cholesterol and triglycerides fell significantly over the 12 months to a similar extent in the two groups . No other significant changes in cardiovascular risk factors were seen . Quality -of-life scores decreased over the 12 months . The decrease was significantly greater among intervention than control women , but not men , for emotional well-being ( P = 0.02 ) , physical well-being ( P = 0.04 ) and social functioning ( P = 0.04 ) . DISCUSSION Provision of general practice -based physical activity advice reinforced three-monthly produced a sustained increase in self-reported physical activity . However , there were no associated changes in clinical measures of cardiovascular risk factors and minimal changes in quality -of-life measures" ]	411897e4-06ff-11f0-808a-c43d1ab1c353
Background Observational studies show that social capital is a protective health factor . Therefore , we aim to assess the currently unclear health impact of social capital interventions targeting older adults . Methods We conducted a systematic review based on a logic model . Studies published between January 1980 and July 2015 were retrieved from MEDLINE , EMBASE , CINAHL , PsycINFO , Cochrane Central Register of Controlled Trials and Web of Science . We included r and omised controlled trials targeting participants over 60 years old and focused on social capital or its components ( eg , social support and social participation ) . The comparison group should not promote social capital . We assessed risk of bias and impact on health outcomes and use of health-related re sources applying a procedure from the Canadian Agency for Drugs and Technologies in Health ( CADTH ) based on vote-counting and st and ardised decision rules . The review protocol was registered in PROSPERO ( reference number CRD42014015362 ) . Results We examined 17 341 abstract s and included 73 papers reporting 36 trials . Trials were clinical ly and method ologically diverse and reported positive effects in different context s , population s and interventions across multiple subjective and objective measures . According to sufficiently reported outcomes , social capital interventions showed mixed effects on quality of life , well-being and self-perceived health and were generally ineffective on loneliness , mood and mortality . Eight trials with high quality showed favourable impacts on overall , mental and physical health , mortality and use of health-related re sources . Conclusions Our review highlights the lack of evidence and the diversity among trials , while supporting the potential of social capital interventions to reach comprehensive health effects in older adults	[ "This report evaluates whether a program for older volunteers , design ed for both benerativity and health promotion , leads to short-term improvements inmultiple behavioral risk factors and positive effects on intermediary risk factors for disability and other morbidities . The Experience Corps ® places older volunteers in public elementary schools in roles design ed to meet schools ’ needs and increase the social , physical , and cognitive activity of the volunteers . This article reports on a pilot r and omized trial in Baltimore , Maryl and . The 128 volunteers were 60–86 years old ; 95 % were African American . At follow-up of 4–8 months , physical activity , strength , people one could turn to for help , and cognitive activity increased significantly , and walking speed decreased significantly less , in participants compared to controls . In this pilot trial , physical , cognitive , and social activity increased , suggesting the potential for the Experience Corps to improve health for an aging population and simultaneously improve educational outcomes for children", "Family caregivers , the “ second victims ” or hidden patients in dementia care , are at risk for social isolation , stress , depression , and mortality . Telephone-based support ( telesupport groups ) represents a practical , low-burden , low-cost source of emotional support . The present study evaluated the feasibility and effectiveness of professionally led telephone-based support groups for female family caregivers of community-dwelling dementia patients . Recruited through various community sources , 103 female caregivers were r and omized to the telesupport group treatment or a control condition . Effects on caregiver burden , depression , and personal gains were evaluated at 6 months , the main end point . Older care-givers ( ≥65 ) in telesupport reported lower depression than control group caregivers did", "AIM This paper is a report of a study to explore the effects of psychosocial group nursing intervention on older people 's feelings of loneliness , social activity and psychological well-being . BACKGROUND Older people 's loneliness is associated with low quality of life , and impaired health , increased use of health and social services and increased mortality . Previous intervention studies have achieved quite modest results . METHOD A r and omized controlled trial was conducted between 2003 and 2006 using a group intervention aim ed at empowering older people , and promoting peer support and social integration . A total of 235 people ( > 74 years ) suffering from loneliness met 12 times with professional leaders in groups . The UCLA Loneliness Scale and Lubben 's Social Network Scale were used at entry , after 3 and 6 months . Psychological well-being was charted using a six-dimensional question naire at baseline and 12 months later . FINDINGS A statistically significantly larger proportion of intervention group participants had found new friends during the follow-up year ( 45 % vs. 32 % , P = 0.048 ) , and 40 % of intervention group participants continued their group meetings for 1 year . However , no differences were found in loneliness or social networks between the groups . Psychological well-being score improved statistically significantly in the intervention groups [ + 0.11 , 95 % confidence interval ( CI ) : + 0.04 to + 0.13 ] , compared with the controls ( + 0.01 , 95 % CI : -0.05 to + 0.07 , P = 0.045 ) . Feeling needed was statistically significantly more common in the intervention groups ( 66 % ) than in controls ( 49 % , P = 0.019 ) . CONCLUSION New sensitive measurements of loneliness and social isolation are needed to measure fluctuations in feelings of loneliness and in social isolation", "This study focused on the assessment of depression among nursing home elders , and on determining the efficacy of an intervention strategy for depression using a geropsychiatric nurse in conjunction with trained older adult volunteers in the role of mental health paraprofessionals . Nursing home residents ( n = 139 ) were assessed for depression using the Geriatric Depression Scale ( GDS ) ; 94 ( 68 % ) were found to have depressive symptomatology . Among those receiving the intervention , depressive symptomatology was significantly reduced , but no significant decline was evident in the control group . The ability of the minimum data set ( MDS ) to detect depression as compared to the GDS was evaluated . Relationships between depression and health status , life satisfaction , and social support were also examined", "The aim of the paper is to critically review the notion of social capital and review empirical literature on the association between social capital and health across countries . The methodology used for the review includes a systematic search on electronic data bases for peer- review ed published literature . We categorize studies according to level of analysis ( single and multilevel ) and examine whether studies reveal a significant health impact of individual and area level social capital . We compare the study conclusions according to the country 's degrees of economic egalitarianism . Regardless of study design , our findings indicate that a positive association ( fixed effect ) exists between social capital and better health irrespective of countries degree of egalitarianism . However , we find that the between-area variance ( r and om effect ) in health tends to be lower in more egalitarian countries than in less egalitarian countries . Our tentative conclusion is that an association between social capital and health at the individual level is robust with respect to the degree of egalitarianism within a country . Area level or context ual social capital may be less salient in egalitarian countries in explaining health differences across places", "Background Interventions relieving the burden of caregiving may postpone or prevent patient institutionalization . The objective of this study was to determine whether a family meetings intervention was superior to usual care in postponing nursing home placement of patients with dementia . Methods A r and omized multicenter trial was conducted among 192 patients with a clinical diagnosis of dementia living at home at enrolment and their primary family caregiver . Dyads of caregivers and patients were r and omized to the family meetings intervention ( n = 96 ) or usual care ( n = 96 ) condition . The intervention consisted of two individual sessions with the primary caregiver and four family counseling sessions that included family members and friends . The primary outcome measure was the time until institutionalization of the patient . Intention-to-treat as well as per protocol analyses were performed . Survival analyses were carried out to evaluate the effectiveness of the intervention . Results During 18 months follow-up 23 of 96 relatives with dementia of caregivers in the intervention group and 18 of 96 relatives with dementia of caregivers in the usual care group were institutionalized . No significant difference between the intervention and the usual care group was found in time until institutionalization ( adjusted hazard ratio ( HR ) 1.46 , 95 % confidence interval ( CI ) 0.78 to 2.74 ) . The per- protocol analysis revealed no significant effect either ( adjusted HR 0.57 , 95 % CI 0.21 to 1.57 ) , although the number of placements among the adherers was relatively low ( 9.4 % ) . A subgroup effect was found for patients ’ age , with a significantly higher risk of institutionalization for ‘ younger ’ patients in the intervention group compared with the usual care group ( adjusted HR = 4.94 , 95 % CI 1.10 to 22.13 ) . Conclusion This family meetings intervention for primary caregivers of patients with dementia did not postpone patient institutionalization more than usual care . Trial Registration : Controlled-Trials.com IS RCT", "PURPOSE Aging , in conjunction with decreasing physical activity , is associated with a range of health problems . Simple , low-maintenance , population -based means of promoting activity to counteract the age-associated decline are required . We therefore assessed the effect of pedometry and buddy support to increase physical activity . METHODS We undertook a clustered r and omized trial ( HKCTR-346 ) of 24 community centers involving 399 older Chinese participants ( ≥ 60 yr ) . Centers were r and omly allocated to 1 ) pedometry and buddy , 2 ) pedometry and no buddy , 3 ) no pedometry and buddy , and 4 ) no pedometry and no buddy with a 2 × 2 factorial design . The trial simultaneously tested the individual and combined effects of the interventions . The intervention groups also received monthly organized group activities to provide encouragement and support . Outcome measures were assessed at 6 and 12 months , including physical fitness and activity and cardiovascular disease risk factors ( anthropometry and blood pressure ) . RESULTS From the 24 centers , 356 volunteers ( 89.2 % ) completed the study . Those receiving the interventions had higher mean physical activity levels at 12 months of 1820 ( 95 % confidence interval ( CI ) = 1360 - 2290 ) and 1260 ( 95 % CI = 780 - 1740 ) MET·min·wk(-1 ) , respectively relative to the decrease in the control groups . The buddy peer support intervention significantly improved mean aerobic fitness ( 12 % [ 95 % CI = 4%-21 % ] ) and reduced both body fat ( -0.6 % [ 95 % CI = -1.1 % to 0.0 % ] ) and time to complete the 2.5-m get-up- and -go test ( -0.27 [ 95 % CI = -0.53 to -0.01 ] s ) . No other improvements in the cardiovascular disease risk factors were observed . The combination of motivational tools was no better than the individual interventions . CONCLUSIONS Both motivational interventions increased physical activity levels , and the buddy style improved fitness . These tools could be useful adjuncts in the prevention of obesity and age-related complications", "Objective : To determine the effectiveness of a counseling and support intervention for spouse caregivers in delaying time to nursing home placement of patients with Alzheimer disease ( AD ) , and identify the mechanisms through which the intervention accomplished this goal . Methods : We conducted a r and omized controlled trial of an enhanced counseling and support intervention compared to usual care . Participants were a referred volunteer sample of 406 spouse caregivers of community-dwelling patients who had enrolled in the study over a 9.5-year period . The intervention consisted of six sessions of individual and family counseling , support group participation , and continuous availability of ad hoc telephone counseling . Structured question naires were administered at baseline and at regular follow-up intervals , every 4 months for the first year and every 6 months thereafter . Cox proportional hazard models were used to test the effects of the intervention on the time to nursing home placement for the patients after controlling for multiple time-invariant and time-dependent predictors of placement . Results : Patients whose spouses received the intervention experienced a 28.3 % reduction in the rate of nursing home placement compared with usual care controls ( hazard ratio = 0.717 after covariate adjustment , p = 0.025 ) . The difference in model-predicted median time to placement was 557 days . Improvements in caregivers ’ satisfaction with social support , response to patient behavior problems , and symptoms of depression collectively accounted for 61.2 % of the intervention ’s beneficial impact on placement . Conclusion : Greater access to effective programs of counseling and support could yield considerable benefits for caregivers , patients with Alzheimer disease , and society", "OBJECTIVES To investigate the effect of self-management group rehabilitation for persons with dementia ( PwD ) and their spouses on their health-related quality of life ( HRQoL ) , the cognition of the PwD , and the costs of health and social services . DESIGN A r and omized controlled trial . SETTING Primary care and memory clinics in the Helsinki metropolitan area , Finl and . PARTICIPANTS PwD ( N = 136 ) and their spouses ( N = 136 ) . INTERVENTION Couples were r and omized to usual care or eight-session self-management groups for PwD and concurrently for their spouses . Sessions aim to enhance self-efficacy and problem-solving skills and to provide peer support . MEASUREMENTS The primary outcome measures were the HRQoL of PwD ( measured using a generic , comprehensive ( 15-dimensional ) , self-administered instrument ( 15D ) ) and spouses ( measured using the R AND -36 ) and the spousal Sense of Competence Question naire ( SCQ ) . Secondary outcome measures were PwD cognition ( Verbal Fluency ( VF ) , Clock Drawing Test ( CDT ) ) and costs of health and social services during 24 months . RESULTS At 3 months , the spouse physical component of the R AND -36 improved ( mean change 1.0 , 95 % confidence interval ( CI ) = -0.5 to 2.4 ) for those undergoing the intervention and worsened for controls ( mean change -2.0 , 95 % CI = -3.5 to -0.4 ) ( P = .006 adjusted for age , sex , baseline value of the physical component of the R AND -36 ) . There were no differences between the groups on the mental component of the R AND -36 , the SCQ , or the 15D . At 9 months , PwD change in VF was -0.38 ( 95 % CI = -1.03 to 0.27 ) in intervention group and -1.60 ( 95 % CI = -2.26 to -0.94 ) for controls ( P = .011 adjusted for age , sex , baseline MMSE score ) . CDT changes were similar to VF changes . Differences in incremental costs between the groups was -436 € per person per year ( 95 % CI = -4,986 to 4,115 ) for PwD ( P = .35 adjusted for age , CDR ) and -896 € per person per year ( 95 % CI = -3,657 to 1,864 ) for spouses ( P = .51 adjusted for PwD age , CDR ) . CONCLUSIONS The intervention had beneficial effects on the HRQoL of spouses and the cognitive function of PwD without increasing total costs . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12611001173987", "Recent scientific work has established both a theoretical basis and strong empirical evidence for a causal impact of social relationships on health . Prospect i ve studies , which control for baseline health status , consistently show increased risk of death among persons with a low quantity , and sometimes low quality , of social relationships . Experimental and quasi-experimental studies of humans and animals also suggest that social isolation is a major risk factor for mortality from widely varying causes . The mechanisms through which social relationships affect health and the factors that promote or inhibit the development and maintenance of social relationships remain to be explored", "OBJECTIVES To investigate the psychosocial effects of the companion robot , Paro , in a rest home/hospital setting in comparison to a control group . DESIGN R and omized controlled trial . Residents were r and omized to the robot intervention group or a control group that attended normal activities instead of Paro sessions . Sessions took place twice a week for an hour over 12 weeks . Over the trial period , observations were conducted of residents ' social behavior when interacting as a group with the robot . As a comparison , observations were also conducted of all the residents during general activities when the resident dog was or was not present . SETTING A residential care facility in Auckl and , New Zeal and . PARTICIPANTS Forty residents in hospital and rest home care . MEASUREMENTS Residents completed a baseline measure assessing cognitive status , loneliness , depression , and quality of life . At follow-up , residents completed a question naire assessing loneliness , depression , and quality of life . During observations , behavior was noted and collated for instances of talking and stroking the dog/robot . RESULTS In comparison with the control group , residents who interacted with the robot had significant decreases in loneliness over the period of the trial . Both the resident dog and the seal robot made an impact on the social environment in comparison to when neither was present . Residents talked to and touched the robot significantly more than the resident dog . A greater number of residents were involved in discussion about the robot in comparison with the resident dog and conversation about the robot occurred more . CONCLUSION Paro is a positive addition to this environment and has benefits for older people in nursing home care . Paro may be able to address some of the unmet needs of older people that a resident animal may not , particularly relating to loneliness", "To evaluate nonpharmacologic interventions , caregivers ( 65 women , 38 men ) and their dementia-diagnosed spouses ( patients ) were r and omized to one of four treatment programs ( cognitive stimulation , dyadic counseling , dual supportive seminar , and early-stage day care ) or to a wait-list control group . Assessment s occurred initially and at postintervention ( 3 months ) . Patients were evaluated on memory , verbal fluency , and problem-solving ability , and caregivers were assessed on marital interaction , emotional status , and physical health , along with stress , coping , and social support . Caregivers also completed a program evaluation . Repeated measures procedures showed that patients in the cognitive stimulation group demonstrated more improvement over time in cognitive outcomes , and caregivers decreased in depressive symptoms . Early-stage day-care and dual supportive seminar group caregivers reported a decrease in hostility and a decrease in use of negative coping strategies , respectively . Although qualitatively derived benefits differed across groups , similarities in program content reduced the potential for quantitative differentiation among the groups", "OBJECTIVE The long-term effect of counseling and support on symptoms of depression was examined in spouse-caregivers of patients with Alzheimer 's disease . METHOD The participants were 406 spouse-caregivers of Alzheimer 's disease patients who lived at home at baseline . The caregivers were r and omly assigned to either a group receiving enhanced counseling and support treatment or a group receiving usual care ( control group ) . Caregivers in the enhanced treatment group were provided with six sessions of individual and family counseling , agreed to join support groups 4 months after enrollment , and received ongoing ad hoc counseling . The Geriatric Depression Scale was administered at baseline and at regular follow-up intervals for as long as the caregiver participated in the study . RESULTS After baseline differences were controlled for , caregivers in the enhanced treatment group had significantly fewer depressive symptoms after the intervention than did the control subjects . These effects were sustained for 3.1 years after baseline , similar across gender and patient severity level , and sustained after nursing home placement or death of the patient . CONCLUSIONS Counseling and support lead to sustained benefits in reducing depressive symptoms in spouse-caregivers of Alzheimer 's disease patients and should be widely available to provide effective , evidence -based intervention for family caregivers", "There is compelling evidence supporting the benefits of increased regular physical activity in older adults . The Experience Corps program in Baltimore MD was design ed in part as a community based approach to increasing physical activity that would also appeal to older adults who have historically not utilized health promotion programs . The Baltimore Experience Corps program places older volunteers in public elementary schools for 15 h a week in roles design ed to improve the academic outcomes of children and , simultaneously , increase the physical , cognitive and social activity of volunteers . This paper reports on the change in physical activity levels among older adults associated with participation in the Baltimore Experience Corps . In a pilot r and omized controlled evaluation , older adults were r and omly assigned to Experience Corps ( EC participants ) or a waiting list control group . Ages ranged from 59–86 years , 96 % were African American , 94 % were women , and 84 % had annual incomes less than $ 15,000 . EC participants were required to serve ≥15 h a week . At follow-up after 4–8 months , an analysis of 113 r and omized volunteers revealed 53 % of the EC participants were more active than the previous year by self-report , as compared to 23 % of the controls ( p increased physical activity in the EC participants as calculated by a kilocalorie per week increase of 40 % , versus a 16 % decrease in the controls ( p=0.49 ) . EC participants who reported “ low activity ” at baseline experienced an average 110 % increase in their physical activity at follow-up . Among the controls who were in the “ low activity ” group at baseline , there was , on average , only a 12 % increase in physical activity ( p=0.03 ) . Among those who were previously active , there was no significant difference ( p=0.30 ) . The pilot results suggest that a high intensity volunteer program that is design ed as a health promotion intervention can lead , in the short-term , to significant improvements in the level of physical activity of previously inactive older adult volunteers", "Debate still surrounds which level of analysis ( individual vs. context ual ) is most appropriate to investigate the effects of social capital on health . Applying multilevel ecometric analyses to British Household Panel Survey data , we estimated fixed and r and om effects between five individual- , household- and small area-level social capital indicators and general health . We further compared the variance in health attributable to each level using intraclass correlations . Our results demonstrate that association between social capital and health depends on indicator type and level investigated , with one quarter of total individual-level health variance found at the household level . However , individual-level social capital variables and other health determinants appear to influence context ual-level variance the most", "OBJECTIVE The objective of this study was to determine the effects of counseling and support on the physical health of caregivers of spouses of people with Alzheimer disease . METHODS A r and omized controlled trial , conducted between 1987 and 2006 at an outpatient research clinic in the New York City metropolitan area compared outcomes of psychosocial intervention to usual care . Structured question naires were administered at baseline and regular follow-ups . A referred volunteer sample of 406 spouse caregivers of community dwelling patients with Alzheimer disease enrolled over a 9.5-year period . Enhanced counseling and support consisted of six sessions of individual and family counseling , support group participation , and continuous availability of ad-hoc telephone counseling . Indicators of physical health included self-rated health ( SRH ) of caregivers and the number of reported illnesses . RESULTS Controlling for baseline SRH ( mean : 7.24 ) , intervention group caregivers had significantly better SRH than control group caregivers based upon model predicted mean scores four months after baseline ( 6.87 versus 7.21 ) , and this significant difference was maintained for two years ( 6.70 versus 7.01 ) . The effect of the intervention on SRH remained significant after controlling for the effects of patient death , nursing home placement , caregiver depressive symptoms and social support satisfaction . Similar benefits of intervention were found for number of illnesses . CONCLUSION Counseling and support preserved SRH in vulnerable caregivers . Enhancing caregivers ' social support , fostering more benign appraisal s of stressors , and reducing depressive symptoms may yield indirect health benefits . Psychosocial intervention studies with biological measures of physical health outcomes are warranted", "Recent years have seen a burgeoning of intergenerational programmes aim ing to improve the well being of participants . However , very few programmes have been formally evaluated . In this paper we report results from a r and omised controlled trial of a school-based intergenerational intervention undertaken in Brazil . R and omly selected sample s of 253 adolescents and 266 elders aged 60 and over resident in the school 's catchment area were administered a question naire including questions on cognitive components of social capital , family relationships , and self-rated health . Participants were then r and omly allocated to control and intervention groups . The intervention comprised participation in a 4 month programme of intergenerational activities in which the elders shared their memories with the students . At the end of the intervention the question naire was re-administered to the sample s. High proportions ( 85 - 95 % ) of both sample s completed the question naires but compliance with the intervention was low in the elderly group . In the analysis of results from the elderly sample , we therefore compared the control group with the group assigned to the intervention ( intention to treat analysis ) . Results showed that adolescents in the intervention group were nearly three times more likely to rate their health as good than those in the control group , but also more likely to judge that most people were selfish . In the elderly sample , those from the intervention group were over twice as likely as those from the control group to report positively on the helpfulness of neighbours ; judge most people to be honest or consider their family relationships as good . There were no significant differences between groups on other outcome measures . These results suggest that structured intergenerational activities may have positive effects on some aspects of social capital for both adolescents and elderly people , although further research is needed to eluci date the processes involved and the extent to which the findings are context specific . This study is the first to use a controlled trial design to evaluate this type of intervention and is valuable in showing that this design can be used in interventions of this kind , and also the difficulties involved", "BACKGROUND Loneliness is a distressing feeling of a lack of satisfying human relationships . It is associated with poor quality of life , impaired health , and increased mortality among older individuals . The study aim was to determine the effects of new psychosocial group rehabilitation on the subjective health , use and costs of health services , and mortality of lonely older individuals . METHODS This r and omized , controlled trial was performed in seven day care centers . A total of 235 older people ( > 74 years ) suffering from loneliness participated . Intervention was implemented in 15 groups ( each with 7 - 8 participants and 2 professional group leaders ) meeting for 3 months altogether 12 times . Group intervention aim ed to empower elderly people , and to promote their peer support and social integration . Intervention was based on the effects of closed-group dynamics . The groups had the following activities according to the participants ' interests : ( a ) therapeutic writing and group psychotherapy , ( b ) group exercise and discussion s , and ( c ) art activities . Group leaders received thorough training and tutoring . Subjective health , use and costs of health services , and mortality were measured . RESULTS At 2 years , survival was 97 % in the intervention group ( 95 % confidence interval [ CI ] , 91 - 99 ) and 90 % in the control group ( 95 % CI , 85 - 95 ) ( p = .047 ) . The intervention group showed a significant improvement in subjective health , thus result ing in significantly lower health care costs during the follow-up : the difference between the groups was -943 euro/person per y ( 95 % CI -1955 to -127 ; p = .039 ) . CONCLUSIONS Psychosocial group rehabilitation was associated with lower mortality and less use of health services", "Study objective : To investigate prospect ively the associations between depression and cognitive social capital ( social trust , sense of belonging , mutual aid ) and structural social capital ( volunteer work and community participation ) . Methods : This was a prospect i ve study that was carried out in the USA . The participants were a nationally representative sample of 724 English-speaking non-institutionalised adults ( 25–74 years old ) who participated in the National Survey of Midlife Development in the United States ( MIDUS ) in 1995–6 and the MIDUS Psychological Experience Follow-Up study in 1998 . Main results : In multivariable adjusted logistic regression analyses , those who trusted their neighbours were less likely to develop major depression ( MD ) during follow-up than those who reported low levels of social capital on these dimensions ( adjusted OR of MD for high vs low trust = 0.43 ; 95 % CI 0.20 to 0.93 , adjusted for MD at baseline , age , gender , race , education , working status , marital status , physical health and extroversion traits ) . Structural dimensions of social capital were not associated with MD in adjusted models . Conclusions : Perceptions of higher levels of cognitive social capital ( trust of neighbours ) are associated with lower risks of developing MD during 2–3 year follow-up . However , after excluding participants with MD at the baseline , the association between trust and MD became non-significant . Structural dimensions were not associated with MD", "Social isolation among the elderly is a concern in developed countries . Using a r and omized trial , this study examined the effect of a social isolation prevention program on loneliness , depression , and subjective well-being of the elderly in Japan . Among the elderly people who relocated to suburban Tokyo , 63 who responded to a pre-test were r and omized and assessed 1 and 6 months after the program . Four sessions of a group-based program were design ed to prevent social isolation by improving community knowledge and networking with other participants and community \" gatekeepers . \" The Life Satisfaction Index A ( LSI-A ) , Geriatric Depression Scale ( GDS ) , And o-Osada-Kodama ( AOK ) loneliness scale , social support , and other variables were used as outcomes of this study . A linear mixed model was used to compare 20 of the 21 people in the intervention group to 40 of the 42 in the control group , and showed that the intervention program had a significant positive effect on LSI-A , social support , and familiarity with services scores and a significant negative effect on AOK over the study period . The program had no significant effect on depression . The findings of this study suggest that programs aim ed at preventing social isolation are effective when they utilize existing community re sources , are tailor-made based on the specific needs of the individual , and target people who can share similar experiences", "Background : After the cardiovascular events of myocardial infa rct ion ( MI ) and coronary artery bypass surgery ( CABS ) , unpartnered older adults are a vulnerable group that may benefit from interventions to improve health outcomes . The purpose of this analysis is to determine if a community-based collaborative peer advisor/advanced practice nurse intervention increased participation in cardiac rehabilitation programs and reduced hospital readmissions after MI and CABS and determine whether the type of cardiovascular event influenced rehospitalization . Subjects and Methods : This study was a r and omized clinical trial that enrolled 247 unpartnered older adults who were single , widowed , or divorced . Subjects were r and omized into 4 groups : st and ard of care group for MI and for CABS and st and ard of care plus the treatment groups for MI and for CABS , for 12 weeks after discharge . There were 163 women/84 men , with a mean age of 76.4 years , who were admitted for MI ( n = 93 ) or CABS ( n = 154 ) and who were enrolled from 5 academic medical centers . The treatment consisted of a community-based intervention of a home visit within 72 hours and telephone calls at 2 , 6 , and 10 weeks from an advanced practice nurse and 12 weekly telephone calls from a peer advisor . Participation in a cardiac rehabilitation program and rehospitalizations were collected at 6 weeks and 3 , 6 , and 12 months by telephone interview . Results and Conclusions : There were significantly more participants in cardiac rehabilitation programs after 3 months in the treatment group , and this increase was seen up to 1 year after MI and CABS . There were no statistical differences , although there were fewer rehospitalizations between 3 and 6 months after MI and CABS in the treatment group compared with the st and ard of care group . Overall , the evidence from this study suggests that a community-based collaborative peer advisor/advanced practice nurse intervention can play a role in promoting active participation in cardiac rehabilitation programs and fewer rehospitalizations in unpartnered older adults after MI and CAGS", "OBJECTIVE Loneliness may predict impaired cognition among older people . The aim of this study was to determine the effects of socially stimulating group intervention on cognition among older individuals suffering from loneliness . DESIGN A r and omized controlled trial . SETTING AND PARTICIPANTS Two hundred thirty-five participants ( ≥75 years ) in seven day care centers in Finl and . INTERVENTION Group intervention was based on the effects of closed-group dynamics and peer support . The three-month intervention was aim ed to enhance interaction and friendships between participants and to socially stimulate them . Each group was facilitated by two specifically trained professionals . In addition to active discussion s , the groups included three types of activities depending on the participants ' interests : 1 ) therapeutic writing ; 2 ) group exercise ; and 3 ) art experiences . MEASUREMENTS Cognition was measured by the Alzheimer 's Disease Assessment Scale ( ADAS-Cog ) , and mental function was measured by the 15D measure . RESULTS The intervention and control groups were similar at baseline with respect to their demographics , disease burden , depression , and cognition . The ADAS-Cog scale improved more in the intervention group than in the control group within the three-month period , with mean changes being -2.6 points ( 95 % confidence interval [ CI ] : -3.4 to -1.8 ) and -1.6 points ( 95 % CI : -2.2 to -1.0 ) , respectively . The dimension of mental function in the 15D showed significant improvement at 12 months in the intervention group ( + 0.048 , 95 % CI : + 0.013 to + 0.085 ) compared with the control group ( -0.027 , 95 % CI : -0.063 to + 0.010 ) . CONCLUSION Psychosocial group intervention improved lonely older people 's cognition ", "The spouse caregivers of 406 patients with Alzheimer 's disease were r and omly assigned to an enhanced counseling and support intervention or to a usual care control condition . Structured interviews were conducted to assess changes in social support and psychosocial outcomes for the 312 caregivers who provided care in the home for at least 1 year . The number of support persons , satisfaction with the support network , and support persons ' assistance with caregiving all increased significantly as a function of the intervention . Structural equation models indicated increased satisfaction with the social support network mediated a significant proportion of the intervention 's impact on caregiver depression . A portion of this mediated effect was further mediated by changes in caregiver stress appraisal s. Implication s for strengthening intervention programs for spouse caregivers of individuals with Alzheimer 's disease are discussed", "We assessed diabetes education and peer support interventions as facilitators of weight loss and glycemic control in a community sample of 79 elderly persons with noninsulin-dependent diabetes mellitus ( NIDDM ) . Different groups received : education only , education and peer support , and no treatment . Peer support was higher in groups where it was actively facilitated . Weight loss and reduction in level of glycemic control occurred within groups receiving both diabetes education and peer support", "Caregivers of Alzheimer 's disease patients often suffer from depression . Using a longitudinal treatment/control study , we examined the effects of a comprehensive support program on depression in spouse-caregivers . This psychosocial intervention program treats the primary caregiver and family members over the entire course of the disease through individual and family counseling , the continuous availability of ad hoc counseling , and support group participation . In the first year after intake , the control group became increasingly more depressed , whereas the treatment group remained stable . By the eighth month , treated caregivers were significantly less depressed than those in the control group . These results suggest that enhancing long-term social support can have a significant impact on depression in caregivers", "OBJECTIVES Being and feeling generative , defined as exhibiting concern and behavior to benefit others , is an important developmental goal of midlife and beyond . Although a growing body of evidence suggests mental and physical health benefits of feeling generative in later life , little information exists as to the modifiability of generativity perceptions . The present study examines whether participation in the intergenerational civic engagement program , Experience Corps ( EC ) , benefits older adults ' self-perceptions of generativity . METHOD Levels of generativity were compared in older adults r and omized to serve as EC volunteers or controls ( usual volunteer opportunities ) in the Baltimore Experience Corps Trial at 4- , 12- , and 24-month evaluation points over the 2-year trial . Analyses utilized intention-to-treat and complier average causal effects ( CACE ) analyses which incorporate degree of intervention exposure in analytic models . RESULTS Participants r and omized to the EC group had significantly higher levels of generative desire and perceptions of generative achievement than controls at each follow-up point ; CACE analyses indicate a dose-response effect with a greater magnitude of intervention effect with greater exposure to the EC program . DISCUSSION Results provide the first-ever , large-scale experimental demonstration that participation in an intergenerational civic engagement program can positively alter self-perceptions of generativity in older adulthood" ]	41189816-06ff-11f0-808a-c43d1ab1c353
OBJECTIVES The aim of the study was to systematic ally review the effects of the adrenoreceptor A1D antagonist naftopidil in the management of lower urinary tract symptoms ( LUTS ) . METHODS A structured and comprehensive MEDLINE search was conducted for original articles , review s , and metanalyses assessing the clinical pharmacology as well as the safety of naftopidil in the treatment of LUTS secondary to BPH . English- language publications dating from 1950 to 2013 were considered . RESULTS In the considered timeframe , 14 r and omized clinical trials ( RCT ) were reported . Overall , the outcome measures assessed in the various reports included in the present review were changes from baseline in : International Prostate Symptom Score ( IPSS ) , quality of life ( QoL ) score , maximum urinary flow rate ( Qmax ) , residual volume ( PVR ) , and adverse effects . Although additional well design ed , worldwide , placebo-controlled and r and omized studies are necessary to confirm the long-term outcomes of naftopidil pharmacotherapy , current data suggest that naftopidil administration in BPH patients provides comparable improvements in total IPSS , QoL , and urinary symptoms from baseline relative to 0.2 mg/d tamsulosin and 8 mg/d silodosin . However , improvements in Qmax are generally less with naftopidil than with tamsulosin . Reported adverse effects related to naftopidil administration are negligible and usually mild . CONCLUSION It remains unknown whether the data reported on naftopidil in the Japanese population are applicable in symptomatic BPH patients from western countries given that : ( 1 ) no English- language clinical trials have compared naftopidil to placebo in Western countries ; ( 2 ) all clinical trials available were carried out in Japan ; ( 3 ) in the comparative studies with tamsulosin , the dose of this drug was lower than the recommended dose in Western countries ; ( 4 ) no data from long-term clinical trials evaluating drug safety beyond 18 weeks	[ "Purpose The efficacy of a loading dose of α1-adrenoreceptor antagonist for patients with benign prostate hyperplasia who did not improve at a low dose has not been determined . We performed a prospect i ve study to estimate the efficacy of incremental naftopidil administration . Methods The efficacy of naftopidil was examined based on changes in the International Prostate Symptom Score ( IPSS ) . We defined a “ responder ” as a patient who improved by ≥5 points in IPSS total score . All patients were administered naftopidil at 50 mg/day for 12 weeks , and nonresponders at 50 mg/day were increased to 75 mg/day . Efficacy was finally evaluated after an additional 12 weeks of administration at 75 mg/day . Results Among 122 patients whose data could be analyzed , the efficacy rate after administration at 50 mg/day was 52.5 % . In all IPSS items except urgency score , the responders had significantly higher ( poorer ) values than nonresponders before the start of treatment . Of 40 patients whose dose was increased to 75 mg/day and whose data could be analyzed , prostate volume in the responder group ( 9 patients ) was significantly smaller than that in the nonresponder group ( 31 patients ) . Multivariate analysis showed that patients with improved IPSS total score , voiding symptoms , urgency , and weak stream after administration of 50 mg/day naftopidil were more likely to improve after a dose increase . Conclusions A dose increment of naftopidil to 75 mg/day may be useful in patients with BPH who did not improve at 50 mg/day", "OBJECTIVES To examine the effect of alpha 1D/A adrenoceptor inhibitor naftopidil on health-related quality of life ( QOL ) in men with benign prostatic hyperplasia ( BPH ) . METHODS A total of 56 newly diagnosed patients with symptomatic BPH were prospect ively enrolled and treated with 50 mg naftopidil daily for more than 12 weeks . All underwent pre-treatment documentation of lower urinary tract symptoms , QOL assessment using the international prostate symptom score ( IPSS ) and King 's Health Question naire ( KHQ ) , and uroflowmetry . A post-treatment assessment was performed at 12 weeks . RESULTS IPSS scores as well as QOL index showed a significant improvement after naftopidil administration . Similarly , all seven domains except general health perceptions and social limitations in the KHQ question naire were significantly improved . When dividing the patients into overactive bladder ( OAB ) and non-OAB groups , only the OAB group showed significant improvement in almost all the domains of KHQ . Change ratios of the IPSS were not associated with those of KHQ domain scores in the OAB group . On the other h and , in the non-OAB group more domains presented improvements , which were associated with those of IPSS scores . CONCLUSIONS Twelve-week treatment with naftopidil for symptomatic BPH patients is associated with significant improvement in the IPSS , QOL index , maximum urinary flow rate , post-void residual urine volume ( PVR ) and almost all domains in KHQ . KHQ is useful for the evaluation of clinical response in BPH patients , particularly in those with associated OAB", "This was a multicenter r and omized trial to investigate the clinical efficacy and the impact on sexual function of alpha-1A selective silodosin and alpha-1D selective naftopidil for treatment of benign prostatic hyperplasia . A total of 97 patients with lower urinary tract symptoms/benign prostatic hyperplasia who had an International Prostate Symptom Score of 8 or more were r and omly assigned to receive silodosin ( 8 mg/day , n = 53 ) or naftopidil ( 75 mg/day , n = 44 ) . Before and 4 , 8 and 12 weeks after treatment , International Prostate Symptom Score and its quality of life score were used to assess lower urinary tract symptoms . Also , International Index of Erectile Function-5 , and an original question naire were used to evaluate erectile function and ejaculation for sexually active patients , respectively . The silodosin group showed advantages in terms of voiding symptoms and quality of life of International Prostate Symptom Score when compared with the naftopidil group . Both silodosin and naftopidil showed no significant effect on International Index of Erectile Function-5 . A total of 23 sexually active patients in the silodosin group experienced more ejaculatory impairment than 21 patients in the naftopidil group , with a decrease of ejaculation volume ( 87 % vs 40 % , P = 0.003 ) , prolonged time to ejaculation ( 56 % vs 33 % , P = 0.027 ) and decrease of orgasm ( 50 % vs 39 % , P = 0.027 ) . These results suggest that alpha-1A selective blockers are more effective for voiding symptoms , whereas alpha-1D selective blockers offer a minor degree of ejaculatory dysfunction", "Naftopidil , approved only in Japan , is an α1-adrenergic receptor antagonist ( α1-blocker ) used to treat lower urinary tract symptoms ( LUTS ) suggestive of benign prostatic hyperplasia ( BPH ) . Different from tamsulosin hydrochloride and silodosin , in that it has higher and extremely higher affinity respectively , for the α1A-adrenergic receptor subtype than for the α1D type , naftopidil has distinct characteristics because it has a three times greater affinity for the α1D-adrenergic receptor subtype than for the α1A subtype . Although well- design ed large-scale r and omized controlled studies are lacking and the optimal dosage of naftopidil is not always completely determined , previous reports from Japan have shown that naftopidil has superior efficacy to a placebo and comparable efficacy to other α1-blockers such as tamsulosin . On the other h and , the incidences of ejaculatory disorders and intraoperative floppy iris syndrome induced by naftopidil may be lower than for tamsulosin and silodosin having high affinity for the α1A-adrenergic receptor subtype . However , it remains unknown if the efficacy and safety of naftopidil in Japanese is applicable to white , black and Hispanic men having LUTS/BPH in western countries", "Objectives To examine the mechanism underlying improvements in nocturia by α1-blockers , we investigated whether the α1-blocker naftopidil acts on nocturia with sleep disturbance using a frequency/volume chart ( FVC ) . Methods A total of 56 male patients with lower urinary tract symptoms were enrolled . The inclusion criteria were as follows : eight or more points on the I-PSS ; three or more points on the I-PSS score for nocturia ; and prostate volume larger than 20 ml . Patients received 50 mg of naftopidil once daily for 4 weeks , and non-responders received 75 mg for another 4 weeks . All patients were examined , and their data entered into FVC for 2 days before and after administration of naftopidil . Quality of sleep was also evaluated using modified Pittsburgh sleep quality index ( PSQI ) . Results Patients with sleep quality scores of three or four were assigned to sleep disturbance group ( n = 33 ) , while those with scores of less than three were assigned to non-disturbance group ( n = 23 ) . After administration of naftopidil , total I-PSS decreased and nocturia score decreased from 3.5 to 2.6 ( P 0.01 ) . Total mean score of modified PSQI in sleep disturbance group became significantly lower after administration of naftopidil ( from 16.9 to 14.0 ; P significantly decreased nocturnal urine volume , result ing in a decrease in the nocturnal polyuria index in both sleep disturbance and non-disturbance groups . Conclusion These results suggest that α1-blockers have the ability to normalize sleep disorders . Naftopidil improved nocturnal polyuria regardless of the presence of sleep disturbance , meaning that it might directly reduce nocturnal urine production", "Objectives . To examine the feature of men who benefit from dose escalation of naftopidil for lower urinary tract symptoms ( LUTSs ) . Methods . Based on the IPSS , men reporting LUTS were prospect ively studied using 50 mg/day of naftopidil for the first 4 weeks ; satisfied patients continued its 50 mg/day ( n = 11 ) , and those reporting unsatisfactory improvement received its 75 mg/day ( n = 35 ) for the next 4 weeks . Results . The 75 mg group showed improvement in the total IPSS and QOL score in a dose-dependent manner ( at 4 weeks : P The baseline slow stream score alone was higher in the 75 mg group ( P = .013 ) . The rate of change in the QOL score during the initial 4 weeks ( ΔQOL ) and Δnocturia was smaller in the 75 mg group ( P . Men with high slow stream score and unsatisfactory improvement in nocturia may benefit from dose escalation of naftopidil ", "PURPOSE We examined the correlation between the expression of alpha1-adrenoceptor subtype mRNA in the prostate and the clinical efficacy of subtype selective alpha1-adrenoceptor antagonists . We discuss the possibility of individualizing drug therapy in patients with benign prostatic hyperplasia . MATERIAL S AND METHODS A total of 33 patients r and omized to the tamsulosin group and 28 r and omized to the naftopidil group were enrolled in this study . Each group of patients was administered 0.2 mg tamsulosin hydrochloride or 50 mg naftopidil daily for 12 weeks . Four prostate needle biopsy specimens were obtained from the transition zone to examine the expression of alpha-adrenoceptor subtypes . Specimens were stored at -80 C until used for TaqMan quantitative reverse transcriptase-polymerase chain reaction , which was performed after 12 weeks of treatment . RESULTS Based on the results of quantitative reverse transcriptase-polymerase chain reaction the tamsulosin and naftopidil groups were grouped into alpha1a-adrenoceptor dominant ( 22 and 12 patients ) and alpha1d-adrenoceptor dominant ( 11 and 16 , respectively ) subgroups . The efficacy of tamsulosin hydrochloride and naftopidil differed depending on the dominant expression of the alpha1-adrenoceptor subtype in the prostate . Tamsulosin hydrochloride was more effective in patients with dominant expression of the alpha1a-adrenoceptor subtype , whereas naftopidil was more effective in those with dominant expression of the alpha1d-adrenoceptor subtype . CONCLUSIONS The expression level of alpha1-adrenoceptor subtype mRNA in the prostate could be a predictor of the efficacy of subtype selective alpha1-adrenoceptor antagonists in patients with benign prostatic hyperplasia . This result implies that genetic differences are responsible for the diverse responses to these drugs", "OBJECTIVES The clinical usefulness of naftopidil was evaluated in 122 patients with benign prostatic hyperplasia for urinary tract symptoms and signs , focused in particular on nocturia . METHODS A total of 122 patients with BPH whose symptoms did not improve after 6 weeks of tamsulosin administration were enrolled . After the treatment was followed by a washout period with placebo , patients were prescribed 75 mg of naftopidil to be taken after dinner for 6 weeks , and the efficacy was re-evaluated . All the drugs used were unidentified , and attention was given to not have the patients recognize the change in the drug given . The primary purpose of this study was the improvement of nocturia in patients with a poor response to tamsulosin . The clinical efficacy of naftopidil was defined as significant improvement in International Prostate Symptom Score , quality -of-life index , and maximal urinary flow rate . RESULTS After 6 weeks of naftopidil administration , significant improvements in daytime and nighttime frequency , International Prostate Symptom Score , quality -of-life index , maximal flow rate , average flow rate , and bladder compliance were examined . On the International Prostate Symptom Score question naire , improvement in the sensation of the bladder not emptying and a reduction in nighttime frequency stood out . Moreover , detrusor overactivity was observed in 40 patients before the start of treatment and was eliminated in 31 . The effective rate of this study was 69.7 % ( 85/122 ) . CONCLUSIONS Naftopidil has novel effects in patients with BPH whose main complaints are storage and voiding symptoms , especially that of nocturia of > or=3 times , as well as in patients with a low compliance bladder and detrusor overactivity , who did not respond to tamsulosin", "AIM The aim of this study was to compare the efficacy and safety of alpha1-adrenoceptor ( alpha1-AR ) antagonist monotherapy with combination therapy using alpha1-AR antagonist and anticholinergic agent for benign prostatic hyperplasia ( BPH ) with storage symptoms as the chief complaint . METHODS In this prospect i ve comparative study , either 25 - 75 mg/day of naftopidil monotherapy ( monotherapy group ) or combination therapy using 25 - 75 mg/day of naftopidil and an anticholinergic agent ( 10 - 20 mg/day of propiverine hydrochloride or 2 - 6 mg/day of oxybutynin hydrochloride ; cotherapy group ) were administered for 12 weeks to 101 BPH patients with storage symptoms . RESULTS International prostate symptom score ( IPSS ) and quality of life ( QOL ) index improved significantly in both groups , with no marked differences between groups . Maximum flow rate ( Qmax ) and residual urine volume ( RUV ) tended to improve in both groups , again with no marked differences between groups . However , median post-therapeutic RUV was significantly worse for the cotherapy group ( 45.0 mL ) than for the monotherapy group ( 13.5 mL ; P = 0.0210 ) . Ratio of patients with increased RUV was also significantly worse for cotherapy ( 22.9 % ) than for monotherapy ( 5.0 % ; P = 0.038 ) . CONCLUSIONS Although the anticholinergic dosage was low , the present results suggest that naftopidil monotherapy was as useful as combination therapy of naftopidil and an anticholinergic agent . Therefore , naftopidil is a useful agent as the first choice in BPH patients with storage symptoms", "BACKGROUND The present study investigated the efficacy , safety , and utility of starting an alpha(1d)-selective antagonist , naftopidil , at 75 or 25 mg/day in patients with lower urinary tract symptoms ( LUTS ) associated with benign prostatic hyperplasia ( BPH ) . METHODS In this prospect i ve comparative study , the subjects comprised 153 patients with LUTS associated with BPH . Patients were r and omized to receive either 25 mg/day ( Group LD ) or 75 mg/day ( Group HD ) of naftopidil for 4 weeks . The lower urinary tract disease symptom score ( LUTDSS ) , the International Prostate Symptom Score ( IPSS ) , the Quality of life assessment index , the maximum flow rate ( Q(max ) ) , and the residual urine volume were compared between the groups . RESULTS In both groups , the LUTDSS and the IPSS were significantly improved at the endpoint and no significant intergroup differences were identified . However , the improvement in the Q(max ) was significantly better for Group HD than for Group LD . The overall efficacy did not differ significantly between the groups . The degree of improvement in voiding symptoms and LUTDSS among patients with moderate symptoms was significantly greater for Group HD than for Group LD . The frequency of adverse reactions did not differ significantly between the groups . CONCLUSIONS Starting administration at 75 mg/day rather than 25mg/day is helpful for LUTS associated with BPH for patients with moderate symptoms , particularly in improving voiding symptoms . The 75 mg/day administration was considered to be a recommendable therapeutic dose in some patients", "There is no consensus on the evaluated efficacy of individual alpha(1)-blockers in the treatment of lower urinary tract symptoms ( LUTS ) associated with benign prostatic hyperplasia ( BPH ) . This study compared the clinical benefits of tamsulosin hydrochloride with those of naftopidil in BPH . Men aged 54 - 84 years with a main complaint of BPH were r and omly assigned to receive consecutive treatment with tamsulosin then naftopidil ( T-N group , 25 patients ) , or naftopidil then tamsulosin hydrochloride ( N-T group , 20 patients ) . The therapeutic effects were compared in a crossover design . Administration was continued for 28 days in each treatment period . Both groups showed similar improvements during the first treatment period . However , during the second treatment period after crossover , therapeutic effects were greater in the N-T group . Tamsulosin was more effective than naftopidil on intermittency , nocturia and quality of life scores . Tamsulosin and naftopidil have different efficacy profiles for LUTS associated with BPH", "OBJECTIVES To investigate the benefit of alpha1-adrenoceptor antagonist naftopidil on the quality of life ( QOL ) of patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia ( BPH/LUTS ) . METHODS A total of 99 men with BPH/LUTS were prospect ively recruited . The Short Form-8 ( SF-8 ) was used for generic QOL assessment and each parameter was compared with the norm in these patients . Longitudinal changes were evaluated using the SF-8 and the International Prostatic Symptoms Score ( I-PSS ) at baseline , 4 and 8 weeks after naftopidil administration . The relationship between SF-8 and I-PSS was analyzed . RESULTS Five of eight components in the SF-8 were significantly lower than the Japanese national norm at baseline . SF-8 score was improved by naftopidil at 4 and 8 weeks in general health ( GH ) and physical component summary ( PCS ) in the patients in their 70s . Mental health ( MH ) and mental component summary ( MCS ) were improved at 8 weeks in patients in their 60s . When analyzing the whole cohort , SF-8 GH , role emotional ( RE ) and MH had improved at 8 weeks , which was similar to the norm , and bodily pain ( BP ) results were better . Compared with the baseline , total I-PSS , storage/voiding symptoms and QOL index scores improved significantly under naftopidil . Each component of I-PSS ( except for hesitancy ) correlated with SF-8 sub-scales ( except for BP ) to some extent . CONCLUSIONS BPH/LUTS impairs generic QOL , which is improved by naftopidil treatment . SF-8 can be a useful instrument to assess the efficacy of BPH/LUTS treatment because its simplicity to complete and analyze , and its meaningful relationship to I-PSS", "OBJECTIVE To evaluate treatment failure during a 4-year follow-up period after administration of naftopidil for patients with lower urinary tract symptoms ( LUTS ) suggestive of benign prostatic hyperplasia ( BPH ) in real-life clinical practice . MATERIAL AND METHODS A total of 247 patients with LUTS/BPH who had an International Prostate Symptom Score ( IPSS ) of > or = 8 were enrolled in the study . Naftopidil , 50 mg/day , was given to the patients . They were followed for 4 years with periodic evaluation . Treatment failure was defined as conversion to other medical treatment or to surgery . RESULTS Of the 247 patients , treatment failure occurred in 42 ( 17.0 % ) during the 4-year follow-up period . The 4-year treatment failure rate was on the Kaplan-Meier curve 35.0 % . Among parameters assessed at baseline , prostate volume ( PV ) was the only significant determinant of treatment failure : patients with a PV of > or = 35 ml had a 2.1 times higher hazard of treatment failure than those with a PV of naftopidil had a 3.5 times higher hazard than those having a mild/moderate IPSS ( 95 % CI 1.34 - 9.26 ; p=0.01 ) . After 4 years , 200 patients ( 81 % ) had stopped taking naftopidil because of adverse events , treatment failure , loss to follow-up , etc . CONCLUSIONS There were significant improvements in IPSS and urinary flow rate with naftopidil although it is unknown whether these improvements were significantly larger than the placebo effect as the study was non-r and omized . However , only 19 % of patients were known to have continued with the same medication for 4 years in real-life clinical practice . Patients who have a large prostate at baseline and a severe IPSS at 12 weeks after treatment are more likely to have treatment failure , although a prospect i ve study is needed to confirm this", "Purpose : To assess the incidence and possible causative factors of a newly recognized syndrome , the intraoperative floppy iris ( IFIS ) . Setting : Clinical practice s in Los Altos and San Rafael , California , USA . Methods : A retrospective chart review of consecutive cataract surgeries performed in a 2‐surgeon practice over a 12‐month period ( 706 eyes ; 511 patients ) was used to assess the percentage of cataract patients on systemic sympathetic α‐1 antagonist medications as well as the percentage of patients who manifested the IFIS . A separate prospect i ve study of 900 consecutive cases ( 741 patients ) performed by another surgeon was used to determine the incidence of IFIS and the percentage of these patients who were taking α‐1 antagonist medications . Results : Three percent ( 16/511 ) of the patients in the retrospective study , representing 3.0 % ( 25/706 ) of the total eyes , were taking tamsulosin ( Flomax ) for benign prostatic hypertrophy . The overall prevalence of IFIS was 2.0 % ( 10/511 patients ) . The syndrome was noted intraoperatively in 63.0 % ( 10/16 ) of the tamsulosin patients but in none of the 11 patients on other systemic α‐1 blockers . In the prospect i ve study of 900 consecutive cataract surgeries , the prevalence of IFIS was 2.2 % ( 16/741 patients ) . Ninety‐four percent ( 15/16 ) of the IFIS patients were taking or had taken systemic tamsulosin . Twenty‐six patients ( 36 eyes ) in the 2 studies had IFIS associated with systemic tamsulosin . Sphincterotomies and mechanical pupil stretching were ineffective in maintaining adequate pupil dilation in this surgical population . Conclusion : Intraoperative floppy iris syndrome occurred in approximately 2 % of a cataract surgery population and appeared to be caused by tamsulosin , a systemic sympathetic α‐1A antagonist medication that is the most frequently prescribed medication for benign prostatic hypertrophy", "Introduction : We examined the tolerability of dosage methods of naftopidil in the treatment of male lower urinary tract symptoms associated with benign prostatic hyperplasia ( BPH/male LUTS ) . Patients and Methods : A total of 80 patients with BPH/male LUTS who had an International Prostate Symptom Score ( IPSS ) ≧8 and IPSS quality of life ( QoL ) ≧2 were enrolled and r and omly administered naftopidil for 8 weeks at either 75 mg once daily ( OD ) in the evening ( group O ; n = 41 ) or 25 mg thrice daily ( TID ) in the morning , afternoon and evening ( group T ; n = 39 ) . Results : IPSS total score , IPSS-QoL and BPH impact index ( BII ) were significantly improved for both groups at 8 weeks after starting treatment compared to baseline . IPSS total score and daytime and 24-hour voiding frequencies were significantly improved at 8 weeks after starting treatment for group O in comparison to group T. Group O showed a significantly better degree of change in BII in comparison to group T. Conclusions : Naftopidil 75 mg OD in the evening was better tolerated than naftopidil 25 mg TID for the objective parameter and BII", "PURPOSE We evaluate the effect of tolterodine combined with tamsulosin on quality of life in patients with bladder outlet obstruction and concomitant detrusor instability . MATERIAL S AND METHODS The study included 50 consecutive patients with urodynamically proven mild or moderate bladder outlet obstruction and concomitant detrusor instability . All patients were initially treated with 0.4 mg . tamsulosin orally once a day . A week later the patients were r and omly allocated into group 1 - 25 who continued treatment with tamsulosin only and , group 2 - 25 who also received 2 mg . tolterodine orally twice daily . Reevaluation with a quality of life question naire and urodynamic study was performed after 3 months . RESULTS Two patients from group 2 stopped tolterodine while 1 patient from each group stopped tamsulosin because of hypotension . Analysis revealed statistically significant improvement in quality of life scores only in group 2 patients ( mean score 525.0 and 628.4 before and after treatment , respectively , 2-sided t test p = 0.0003 ) . A significant difference was noted in both groups after treatment for maximum flow rate and volume at first contraction . Additionally , in group 2 , a statistically significant difference was observed for maximum detrusor pressure and maximum unstable contraction pressure after treatment . CONCLUSIONS Combination treatment with an alpha-blocker ( tamsulosin ) plus an anticholinergic ( tolterodine ) improves quality of life in patients with bladder outlet obstruction and concomitant detrusor instability . Interestingly , no acute urinary retention was observed and tolterodine did not affect the quality of urine flow or residual urine volume . The proposed combination appears to be an effective and relatively safe treatment option in patients with bladder outlet obstruction and detrusor instability", "The pharmacokinetics of naftopidil , a novel alpha-1 adrenoceptor-blocking antihypertensive , were investigated in ten patients ( 9M/1F ) with hepatic dysfunction after oral administration ( 50 mg , tablet ) and after an intravenous infusion of 5.0 mg over 2 minutes . Results were compared to a control group of 12 healthy subjects ( 6M/6F ) of a previous investigation , which was carried out according to the identical study protocol . The pharmacokinetic parameters obtained for the i.v . administration were comparable in both groups ( half life 3.6 + /- 3.4 hours in liver-impaired subjects versus 3.3 + /- 2.1 hours in controls ; clearance 11.9 + /- 4.7 ml/minute/kg versus 11.0 + /- 1.6 ml/minute/kg ) . Following oral administration the plasma levels and half-life times of naftopidil were significantly increased in liver impairment ( t1/2 16.6 + /- 19.3 hours versus 5.4 + /- 3.2 hours in controls ; P = 0.012 ) . Mean values for the absolute bioavailability in patients with hepatic dysfunction were significantly higher ( mean 75 % , median 53 % , range 13.4 - 211.0 % ) compared to healthy subjects ( mean 17 % , median 16 % , range 6.7 - 29.6 % , P = 0.001 ) . Reduction of functional hepatic blood flow in chronic liver disease or , as evidence d in one case as a consequence of shunt surgery , is the probable cause of the observed alteration in naftopidil kinetics . This phenomenon occurred only following the oral 50 mg dose whereas the intravenous 5 mg dose obviously still could be normally h and led . Naftopidil demethylation and hydroxylation were both less and non-uniformly affected . The pharmacokinetic findings suggest that in patients with severe hepatic impairment or evidence for marked changes in hepatic blood flow the dose of naftopidil may require adjustment to the lower end of the therapeutic range and /or may be limited to once daily . However , before definite conclusions can be drawn , further steady-state studies are required . Despite the pharmacokinetic discrepancies no difference in drug tolerability was seen between patients and healthy subjects", "Introduction : To investigate the incidence of ejaculatory disorders caused by naftopidil and tamsulosin in patients with lower urinary tract symptoms ( LUTS ) suggestive of benign prostatic hyperplasia ( BPH ) . Material s and Methods : Ninety-five patients with LUTS/BPH who had International Prostate Symptom Scores ( IPSS ) of 8 or more were r and omly assigned to receive naftopidil ( 50 mg/day , n = 48 ) or tamsulosin ( 0.2 mg/day , n = 47 ) . Before and 12 weeks after treatment , a question naire was used to evaluate ejaculation . Results : Among men who had sexual activity during the 12 weeks , the proportion who reported an abnormal feeling on ejaculation was higher in the tamsulosin group ( 16.7 % ) than in the naftopidil group ( 7.4 % ) , although the difference was not significant ( p = 0.402 ) . The proportion of men who reported reduced ejaculatory volume after treatment was significantly higher in the tamsulosin group ( 96.0 % ) than in the naftopidil group ( 73.1 % , p = 0.0496 ) . On the other h and , the improvements in IPSS and the quality of life index were significantly higher in the tamsulosin group than in the naftopidil group . Conclusions : Tamsulosin may cause a higher incidence of ejaculatory disorders than naftopidil , although the efficacy of 0.2 mg tamsulosin may be better than that of 50 mg naftopidil", "PURPOSE To evaluate the incidence of Intraoperative Floppy Iris syndrome ( IFIS ) in relation to the usage of alpha(1)-adrenoceptor antagonists . DESIGN Prospect i ve , interventional case series . METHODS In 2,643 consecutive eyes of 1,968 patients undergoing cataract surgery , occurrence of IFIS and use of alpha(1 ) antagonists were recorded . RESULTS IFIS was observed in 29 eyes ( 1.1 % ) of 25 male patients , all of whom were receiving alpha(1 ) antagonists . In those receiving systemic tamsulosin , alpha(1A ) selective antagonist , IFIS developed in 25 ( 43.1 % ) of 58 eyes . In those receiving systemic naftopidil , alpha(1A ) and alpha(1D ) antagonists , IFIS was found in 4 ( 19.0 % ) of 21 eyes . There was no case of IFIS in patients who received other systemic alpha(1 ) antagonists and in eyes treated with bunazosin eyedrops , a nonselective alpha(1 ) antagonist . CONCLUSIONS IFIS occurred in 1.1 % of cases treated with systemic alpha(1A)-adrenoceptor antagonists for benign prostatic hypertrophy . Topical nonselective alpha(1 ) antagonist did not induce IFIS", "OBJECTIVES In order to compare the clinical efficacy of naftopidil ( Naf ) and tamsulosin hydrochloride ( Tam ) , which differ in their selectivity to alpha receptor subtypes , we performed a multi-center prospect i ve r and omized controlled study . METHODS Men complaining of lower urinary tract symptoms due to benign prostatic hypertrophy , were r and omized into two treatment groups : one receiving 50 mg Naftopidil daily ( Naf group , n = 31 pts ) , and one receiving 0.2 mg Tam once daily ( Tam group , n = 28 pts ) . Baseline symptom scores were compared to those at 2 weeks and at the end of the observation period ( 6 - 8 weeks ) . RESULTS In the Naf group at 2 weeks , the score of the daytime frequency significantly improved from 3.5 to 2.2 ( P = 0.03 ) , and the score of nocturia improved significantly from 3.5 to 2.2 ( P = 0.0004 ) , respectively . In the Tam group at 2 weeks , however , no significant improvement was noted in the increased score of daytime frequency ( P = 0.1 ) or nocturia ( P = 0.2 ) . At 2 weeks , the storage symptom score of the frequency to the combined score of daytime frequencies and the score of nocturia was better in the Naf group ( improved from 7.0 to 4.4 , P = 0.0017 ) than in the Tam group ( from 6.8 to 4.9 , P = 0.08 ) ( P lower urinary tract symptoms were comparable . CONCLUSIONS Naf demonstrated a significant early response to improve storage symptoms at 2 weeks , including daytime frequency and nocturia , compared with Tam", "BACKGROUND The aim of the study presented here was to stratify drug therapy for patients with benign prostatic hyperplasia ( BPH ) displaying various voiding symptoms . METHODS Two different alpha1-adrenoceptor antagonists ; tamsulosin hydrochloride ( Tam ) and naftopidil ( Naf ) , were administered to 96 patients with BPH for 8 weeks in a crossover study . RESULTS With the administration of both drugs , the International Prostate Symptom Score ( I-PSS ) significantly decreased and the maximum urinary flow significantly increased . Whereas Naf monotherapy decreased the I-PSS for storage symptoms , Tam monotherapy decreased the I-PSS for voiding symptoms . In both the Naf-to-Tam and Tam-to-Naf groups , crossover was effective when the initial drug was judged subjectively and objective ly to have been ineffective . Compliance was acceptable with both drugs . CONCLUSION Our results show that either Naf or Tam can be used to treat patients on the basis of objective and subjective assessment of voiding symptoms . Our findings should be helpful for patient guidance and treatment of BPH", "OBJECTIVES To examine the efficacy of dose increase therapy in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia who responded poorly to 50 mg/day of naftopidil . METHODS A total of 95 patients received 50 mg/day of naftopidil for 8 weeks . After this treatment period , they were divided into two groups : the poor responders were defined as those who either had an International Prostate Symptom Score- Quality of Life ≥ 4 or with an International Prostate Symptom Score- Quality of Life of 3 whose International Prostate Symptom Score- Quality of Life improved to naftopidil 50 mg/day ( group B ) . The dose of naftopidil was increased to 75 mg/day in group A , and maintained at 50 mg/day in group B. The treatment was continued for a further 8 weeks . RESULTS The prostate volume at the baseline was significantly larger in group A than group B. The improvement of International Prostate Symptom Score total score , International Prostate Symptom Score- Quality of Life , and voided volume after 8 weeks was significantly better in group B than in group A. However , there was no significant difference in the changes of all parameters between the two groups after 16 weeks . CONCLUSIONS A dose increase to 75 mg/day is an effective treatment strategy in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia who responded poorly to an initial dose of 50 mg/day of naftopidil . Furthermore , a starting dose of 75 mg/day should be considered in patients with a large prostate volume , as this is a predictive factor for dose increase", "OBJECTIVES Silodosin is a novel drug that is highly selective to subtype alpha 1A and , since 2006 , has been used in Japan for treating benign prostatic hyperplasia . This study aim ed to compare the clinical effects of the alpha-adrenoceptor antagonist , silodosin , with those of naftopidil in patients presenting lower urinary tract symptoms associated with benign prostatic hyperplasia . METHODS This was a r and omized , open-label , controlled multicenter study carried out in Japan . Overall , 121 participants with lower urinary tract symptoms associated with benign prostatic hyperplasia were r and omized to receive silodosin ( 4 mg twice daily ) or naftopidil ( 50 mg once daily ) for 4 or 8 weeks . Patients were divided into four groups : the alpha-blocker-naive groups received silodosin ( 35 patients ) or naftopidil ( 33 patients ) and the drug-switching groups changed from tamsulosin to silodosin ( 26 patients ) or naftopidil ( 27 patients ) . The outcomes parameters were the International Prostate Symptom Score , quality of life , maximum urinary flow rate and post-void residual urine volume . P naftopidil significantly improved the total International Prostate Symptom Score and quality of life . However , silodosin obtained significantly better improvement in total International Prostate Symptom Score in the alpha-blocker-naive patients at 4 and 8 weeks . The maximum urinary flow rate and residual urine did not change significantly in all the treatment groups . CONCLUSIONS The present study confirms the clinical usefulness of silodosin in the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia", "Objective . To assess the efficacy and safety of propiverine hydrochloride ( antimuscarinic ) , naftopidil ( α1-adrenoceptor antagonist ) or both in patients with male lower urinary tract symptoms ( LUTS ) suggestive of benign prostatic hyperplasia and concomitant overactive bladder ( OAB ) . Material and methods . Men aged at least 50 years who had a total International Prostate Symptom Score ( IPSS ) of 8 or higher and bladder dairy documenting micturition frequency ( more than eight micturitions/24 h ) and urgency ( more than one episode/24 h ) , with or without urgency urinary incontinence were r and omized into three groups : group N , naftopidil ( 50 mg once daily ) only ; group P , propiverine hydrochloride ( 20 mg once daily ) ; and group NP , naftopidil ( 50 mg once daily ) plus propiverine hydrochloride ( 20 mg once daily ) for a 4-week treatment regimen . Results . A total of 66 men , including 20 in group N , 23 in group P and 23 in group NP , were treated and 58 ( 87.9 % ) completed the 4 weeks of treatment . IPSS improved significantly in groups N and NP . Urinary frequency improved significantly in groups P and NP . Postvoid residual urine volume increased significantly in groups P and NP . Significant improvements in urgency episodes were noted in each group . One patient in group P required catheterization owing to acute urinary retention and another stopped medication because of difficulty in voiding . Conclusion . These results suggest that each treatment showed effectiveness for male LUTS with OAB . However , there are some possibilities of adverse effects with propiverine hydrochloride monotherapy", "OBJECTIVES We analyzed the prevalence and characteristics of lower urinary tract symptoms ( LUTS ) in community-dwelling men aged 80 years and older . METHODS We administered the American Urological Association Symptom Index ( AUA-SI ) by mail to 291 surviving community-dwelling male participants in the Rancho Bernardo Study , a prospect i ve , community-based study of aging . We compared the prevalence , severity , and types of LUTS occurring in men who were > or = 80 years to those RESULTS The mean age was 74.6 years ( st and ard deviation [ SD ] 8.9 , range 48.3 - 97.1 ) . One third of the respondents were > or = 80 years . The mean total AUA-SI score increased steadily by decade of life ( P-trend = .002 ) . The prevalence of LUTS was 70 % in men > or = 80 years and 56 % in men or = 80 years had significantly higher mean total AUA-SI ( P = .05 ) and were more likely to complain of incomplete emptying ( odds ratio [ OR ] 2.12 , 95 % confidence interval [ CI ] 1.06 - 4.18 , P = .02 ) , frequency ( OR 1.83 , 95 % CI 1.00 - 3.31 , P = .03 ) , urgency ( OR 1.76 , 95 % CI 0.96 - 3.20 , P = .05 ) , and weak stream ( OR 1.78 , 95 % CI 1.01 - 3.12 , P = .03 ) . CONCLUSIONS In this cohort of community-dwelling men , prevalence and severity of LUTS increased into the 10th decade of life . Compared to younger men , men > or = 80 years were more likely to complain of incomplete emptying , frequency , urgency , and weak stream . Further studies of LUTS in older men are needed to better delineate these associations" ]	41189852-06ff-11f0-808a-c43d1ab1c353
Use and acceptance of health economic evaluations ( HEEs ) has been much greater in developed than in developing nations . Nevertheless , while developing countries lag behind in the development of HEE methods , they could benefit from the progress made in other countries and concentrate on ways in which existing methods can be used or would need to be modified to fulfill their specific needs . HEEs , as context -specific tools , are not easily generalizable from setting to setting . Existing studies regarding generalizability and transferability of HEEs have primarily been conducted in developed countries . Therefore , a legitimate question for policy makers in Latin America and the Caribbean region ( LAC ) is to what extent HEEs conducted in industrialized economies and in LAC are generalizable to LAC ( trans-regional ) and to other LAC countries ( intra-regional ) , respectively . We conducted a systematic review , search ing the NHS Economic Evaluation Data base ( NHS EED ) , Office of Health Economics Health Economic Evaluation Data base ( HEED ) , LILACS ( Latin America health bibliographic data base ) and NEVALAT ( Latin American Network on HEE ) to identify HEEs published between 1980 and 2004 . We included individual patient- and model-based HEEs ( cost-effectiveness , cost-utility , cost-benefit and cost-consequences analyses ) that involved at least one LAC country . Data were extracted by three independent review ers using a checklist vali date d by regional and international experts . From 521 studies retrieved , 72 were full HEEs ( 39 % r and omized controlled trials [ RCTs ] , 32 % models , 17 % non-r and omized studies and 12 % mixed trialmodeling approach ) . Over one-third of identified studies did not specifically report the type of HEE . Cost-effectiveness and cost-consequence analyses accounted for almost 80 % of the studies . The three Latin American countries with the highest participation in HEE studies were Brazil , Argentina and Mexico . While we found relatively good st and ards of reporting the study ’s question , population , interventions , comparators and conclusions , the overall reporting was poor , and evidence of unfamiliarity with international guidelines was evident ( i.e. absence of incremental analysis , of discounting long-term costs and effects ) . Analysis or description of place-to-place variability was infrequent . Of the 49 trial-based analyses , 43 % were single centre , 33 % multinational and 18 % multicentre national . Main reporting problems included issues related to sample representativeness , data collection and data analysis . Of the 32 model-based studies ( most commonly using epidemiological models ) , main problems included the inadequacy of search strategy , range selection for sensitivity analysis and theoretical justifications . There are a number of issues associated with the reporting and methodology used in multinational and local HEE studies relevant for LAC that preclude the assessment of their generalizability and potential transferability . Although the quality of reporting and methodology used in model-based HEEs was somewhat higher than those from trial-based HEEs , economic evaluation methodology was usually weak and less developed than the analysis of clinical data . Improving these aspects in LAC HEE studies is paramount to maximizing their potential benefits such as increasing the generalizability/transferability of their results	[ "Spontaneous pneumothorax ( SP ) is a disabling condition mostly affecting young , thin and otherwise healthy males . It is usually caused by ruptured pleural blebs . The first treatment is the insertion of a chest tube ( ICT ) but in a great number of patients there is recurrence of the disease . We believe that the video assisted thoracoscopy ( VATS ) is the best treatment possible because it allows us to treat the ruptured bleb radically avoiding any recurrence . In order to prove it , 40 patients admitted in a five-year period , with a SP , were r and omly assigned to be treated by ICT or VATS . The ICT patients were in the hospital a mean time of 7.5 ( 4 to 15 ) days and the VATS patients , 5.3 ( 2 to 7 ) days ( P ICT patients required analgesic drugs during 76.8 + /- 31 hours and VATS patients 38.4 + /- 13 hours ( p ICT group , 8 ( 53 % ) patients had recurrence of the disease and 6 ( 40 % ) had a prolonged air leak , while none of the patients of the VATS group had any complication ( Cost of ICT and VATS were $ 850 and $ 1730 , respectively . According to these results , VATS should be the treatment of choice in SP patients . It treats the cause of the disease . It also reduces the hospitalization time , the use of analgesic drugs post surgery , decreases recurrence of the disease and the cost of the treatment . Moreover , the patients were back to work in less than 10 days", "BACKGROUND The recent recognition that coronary-artery stenting has improved the short- and long-term outcomes of patients treated with angioplasty has made it necessary to reevaluate the relative benefits of bypass surgery and percutaneous interventions in patients with multivessel disease . METHODS A total of 1205 patients were r and omly assigned to undergo stent implantation or bypass surgery when a cardiac surgeon and an interventional cardiologist agreed that the same extent of revascularization could be achieved by either technique . The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at one year . The costs of hospital re sources used were also determined . RESULTS At one year , there was no significant difference between the two groups in terms of the rates of death , stroke , or myocardial infa rct ion . Among patients who survived without a stroke or a myocardial infa rct ion , 16.8 percent of those in the stenting group underwent a second revascularization , as compared with 3.5 percent of those in the surgery group . The rate of event-free survival at one year was 73.8 percent among the patients who received stents and 87.8 percent among those who underwent bypass surgery ( P costs for the initial procedure were $ 4,212 less for patients assigned to stenting than for those assigned to bypass surgery , but this difference was reduced during follow-up because of the increased need for repeated revascularization ; after one year , the net difference in favor of stenting was estimated to be $ 2,973 per patient . CONCLUSION As measured one year after the procedure , coronary stenting for multivessel disease is less expensive than bypass surgery and offers the same degree of protection against death , stroke , and myocardial infa rct ion . However , stenting is associated with a greater need for repeated revascularization", "BACKGROUND The combination of ceftazidime plus aminoglycoside is widely used for the treatment of febrile neutropenic patients but requires multiple daily administration . Because the frequency of Pseudomonas aeruginosa is low in many centers , there is a rationale to test other antibiotic regimens that provide appropriate antibacterial coverage with the advantage of reduced dosing frequency , such as once daily ceftriaxone plus amikacin . METHODS Febrile neutropenic children with leukemia , lymphoma or solid tumors after chemotherapy were included in an open , prospect i ve , r and omized , multinational study comparing once daily ceftriaxone plus amikacin vs. 8-hourly ceftazidime and amikacin . The response to antimicrobial therapy was defined as complete response , improvement or failure . Assessment of adverse events was supplemented by specific definitions of nephrotoxicity , ototoxicity , hepatotoxicity and hypokalemia . Costs were estimated from published values of acquisition costs , delivery costs and hospitalization costs . RESULTS Efficacy was evaluable in 364 of 468 episodes in 265 children . Response rates in ceftriaxone and amikacin vs. ceftazidime and amikacin-treated episodes were 119 of 181 ( 66 % ) vs. 121 of 183 ( 66 % ) , 7 of 181 ( 4 % ) vs. 9 of 183 ( 5 % ) and 55 of 181 ( 30 % ) vs. 53 of 181 ( 29 % ) for complete response , improvement and failure , respectively . Safety profiles were similar with both treatment regimens . The acquisition and administration costs were lower for the ceftriaxone and amikacin regimen . CONCLUSIONS A once daily regimen of ceftriaxone and amikacin is as safe and clinical ly effective as that of three times daily ceftazidime and amikacin for the treatment of febrile neutropenic children with cancer and is more cost-effective . The once daily regimen of ceftriaxone and amikacin is suitable for outpatient treatment", "Background —Our aims were to compare coronary artery bypass grafting ( CABG ) and stenting for the treatment of diabetic patients with multivessel coronary disease enrolled in the Arterial Revascularization Therapy Study ( ARTS ) trial and to determine the costs of these 2 treatment strategies . Methods and Results — Patients ( n=1205 ) were r and omly assigned to stent implantation ( n=600 ; diabetic , 112 ) or CABG ( n=605 ; diabetic , 96 ) . Costs per patient were calculated as the product of each patient ’s use of re sources and the corresponding unit costs . Baseline characteristics were similar between the groups . At 1 year , diabetic patients treated with stenting had the lowest event-free survival rate ( 63.4 % ) because of a higher incidence of repeat revascularization compared with both diabetic patients treated with CABG ( 84.4 % , P stents ( 76.2 % , P = 0.04 ) . Conversely , diabetic and nondiabetic patients experienced similar 1-year event-free survival rates when treated with CABG ( 84.4 % and 88.4 % ) . The total 1-year costs for stenting and CABG in diabetic patients were $ 12 855 and $ 16 585 ( P diabetic patients treated with stenting had a worse 1-year outcome than patients assigned to CABG or nondiabetics treated with stenting . The strategy of stenting was less costly than CABG , however , regardless of diabetic status", "The escalating role played by managed care organizations in the health-care system is reflected in the increased dem and for cost-effectiveness analyses ( CEAs ) to assess the balance between economic impact and clinical efficacy . For example , the high incidence and costs associated with colorectal cancer in Latin America calls for a comprehensive economic evaluation to ensure appropriate allocation of limited health-care funds . In addition , the current call for a \" societal \" perspective of such analyses indicates the need for increased consideration of the concerns of both patient and health-care provider . The introduction of oral tegafur and uracil ( UFT ) provided the opportunity to evaluate the pharmacoeconomic advantage of the new agent compared with the st and ard fluorouracil ( 5-FU ) . Results of this study indicated an economic advantage for oral UFT vs a 5-FU-based regimen in the treatment of colorectal cancer in Brazil and Argentina . It was further noted that the mild toxicity profile of UFT reduced both the number of clinic visits and the need for venipuncture procedures . Noting that oral UFT may have a positive impact on quality of life in addition to its estimated economic benefit , it was concluded that prospect i ve economic research and quality -of-life evaluations are needed to fully assess the pharmacoeconomic impact of oral UFT", "OBJECTIVES The second Primary Angioplasty in Myocardial Infa rct ion ( PAMI-II ) study evaluated the hypothesis that primary percutaneous transluminal coronary angioplasty ( PTCA ) , with subsequent discharge from the hospital 3 days later , is safe and cost-effective in low risk patients . BACKGROUND In low risk patients with myocardial infa rct ion ( MI ) , few data exist regarding the need for intensive care and noninvasive testing or the appropriate length of hospital stay . METHODS Patients with acute MI underwent emergency catheterization with primary PTCA when appropriate . Low risk patients ( age 45 % , one- or two-vessel disease , successful PTCA , no persistent arrhythmias ) were r and omized to receive accelerated care ( admission to a nonintensive care unit and day 3 hospital discharge without noninvasive testing [ n = 237 ] or traditional care [ n = 234 ] ) . RESULTS Patients who received accelerated care had similar in-hospital outcomes but were discharged 3 days earlier ( 4.2+/-2.3 vs. 7.1+/-4.7 days , p = 0.0001 ) and had lower hospital costs ( $ 9,658+/-5,287 vs. $ 11,604+/-6,125 p = 0.002 ) than the patients who received traditional care . At 6 months , accelerated and traditional care groups had a similar rate of mortality ( 0.8 % vs. 0.4 % , p = 1.00 ) , unstable ischemia ( 10.1 % vs. 12.0 % , p = 0.52 ) , reinfa rct ion ( 0.8 % vs. 0.4 % , p = 1.00 ) , stroke ( 0.4 % vs. 2.6 % , p = 0.07 ) , congestive heart failure ( 4.6 % vs. 4.3 % , p = 0.85 ) or their combined occurrence ( 15.2 % vs. 17.5 % , p = 0.49 ) . The study was design ed to detect a 10 % difference in event rates ; at 6 months , only a 2.3 % difference was measured between groups , indicating an actual power of 0.19 . CONCLUSIONS Early identification of low risk patients with MI allowed safe omission of the intensive care phase and noninvasive testing , and a day 3 hospital discharge strategy , result ing in substantial cost savings", "OBJECTIVES This study was design ed to compare freedom from combined cardiac events ( death , angina , myocardial infa rct ion ) at 1- , 3- and 5-year follow-up in patients with multivessel disease r and omized to either percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery . BACKGROUND Percutaneous transluminal coronary angioplasty has been an effective approach in patients with coronary artery disease , but its role in patients with multivessel coronary artery disease is still controversial . METHODS One-hundred twenty-seven patients with multivessel disease and lesions suitable for either form of therapy were r and omized to either coronary artery bypass grafting ( n = 64 ) or coronary angioplasty ( n = 63 ) . In this study we report the immediate results and freedom from combined cardiac events at 1-year follow-up . RESULTS Demographic , clinical and angiographic characteristics were similar in both groups . There were no differences in in-hospital deaths , frequency of periprocedure myocardial infa rct ion or need for emergency revascularization procedures between the two groups . At 1-year follow-up , there were no differences in mortality or in the incidence of myocardial infa rct ion between the groups . However , patients treated with coronary artery bypass grafting were more frequently free of angina , re interventions and combined cardiac events than were patients treated with coronary angioplasty ( 83.5 % vs. 63.7 % , p In-hospital cost and cumulative cost at 1-year follow-up were greater for the coronary artery bypass grafting than for the coronary angioplasty group . CONCLUSIONS No significant differences were found in major in-hospital complications between patients treated with coronary artery bypass grafting or coronary angioplasty . Although at 1-year follow-up there were no differences in survival and freedom from myocardial infa rct ion , patients in the coronary artery bypass grafting group were more frequently free from angina , re interventions and combined events than were patients in the coronary angioplasty group", " Study sample 263 cyst carriers were identified from a sample population of 12,000 ( 2.1 % ) . From these , two groups each totalling 100 , were assigned to either a treatment ( receiving metronidazole ) or control ( receiving placebo ) group . Power calculations ( no details provided ) determined a minimum sample size of 79 . A loss rate of 20 % was estimated by the authors and this determined the two sample size totals , explaining the loss of 63 cyst carriers from the final sample population", "OBJECTIVE To implement an educational program in 10 Latin American countries and to evaluate its effect on the clinical , biochemical , and therapeutic aspects as well as the economic cost of diabetes . RESEARCH DESIGN AND METHODS Educators from each participating country were previously trained to implement the educational model . The patient population included 446 individuals with type 2 diabetes ; all patients were Clinical and therapeutic data and the cost of their pharmacological treatment were collected 6 months before participation in the educational program ( -6 months ) , on entry into the program ( time 0 ) , and at 4 , 8 , and 12 months after initiation of the program . RESULTS All parameters measured had improved significantly ( P fasting blood glucose ( mean + /- SD ) 10.6 + /- 3.5 vs. 8.7 + /- 3.0 mmol/l ; HbA(1c ) 9.0 + /- 2.0 vs. 7.8 + /- 1.6 % ; body weight 84.6 + /- 14.7 vs. 81.2 + /- 15.2 kg ; systolic blood pressure 149.6 + /- 33.6 vs. 142.9 + /- 18.8 mmHg ; total cholesterol 6.1 + /- 1.1 vs. 5.4 + /- 1.0 mmol/l ; and triglycerides 2.7 + /- 1.8 vs. 2.1 + /- 1.2 mmol/l . At 12 months , the decrease in pharmacotherapy required for control of diabetes , hypertension , and hyperlipidemia represented a 62 % decrease in the annual cost of treatment ( $ 107,939.99 vs. $ 41,106.30 [ U.S. ] ) . After deducting the additional cost of glucosuria monitoring ( $ 30,604 ) , there was still a 34 % annual savings . CONCLUSIONS The beneficial results of this educational model , implemented in 10 Latin American countries , reinforce the value of patient education as an essential part of diabetes care . They also suggest that an educational approach promoting healthy lifestyle habits and patient empowerment is an effective strategy with the potential to decrease the development of complications related to diabetes as well as the socioeconomic costs of the disease", "OBJECTIVE To develop and apply a model to assess the economic value of a workplace influenza programme from the perspective of the employer . DESIGN The model calculated the avoided costs of influenza , including treatment costs , lost productivity , lost worker added value and the cost of replacing workers . Subtracted from this benefit were the costs associated with a vaccination programme , including administrative costs , the time to give the vaccine , and lost productivity due to adverse reactions . The framework of the model can be applied to any company to estimate the cost-benefit of an influenza immunisation programme . SETTING The model developed was applied to 4030 workers in the core divisions of a Brazilian pharma-chemical company . RESULTS The model determined a net benefit of $ US121,441 [ 129,335 Brazilian reals ( $ Brz ) ] , or $ US35.45 ( $ Brz37.75 ) per vaccinated employee ( 1997 values ) . The cost-benefit ratio was 1:2.47 . The calculations were subjected to a battery of 1-way and 2-way sensitivity analyses that determined that net benefit would be retained as long as the vaccine cost remained below $ US45.40 ( $ Brz48.40 ) or the vaccine was at least 32.5 % effective . Other alterations would retain a net benefit as well , including several combinations of incidence rate and vaccine effectiveness . CONCLUSIONS The analysis suggests that providing an influenza vaccination programme can incur a substantial net benefit for an employer , although the size of the benefit will depend upon who normally absorbs the costs of treating influenza and compensating workers for lost work time due to illness , as well as the type of company in which the immunisation programme is applied", "OBJECTIVE To analyse the costs and the effectiveness of an intervention of home visits made by nurses to elderly people versus usual care given by the family medicine units . MATERIAL AND METHODS A sample of 4,777 subjects aged 60 years and over covered by the Mexican Institute of Social Security ( Instituto Mexicano del Seguro Social , IMSS ) were screened . Those with a systolic and /or diastolic blood pressure level higher or equal than 160/90 mm Hg were r and omly allocated to the intervention or control groups . The intervention consisted of visits at home by nurses who gave health and lifestyle advice to the participants . The economic evaluation was considered from a health services and patient perspective . Direct and indirect costs were calculated as incremental . Effectiveness was measured in terms of cost per millimetre of mercury reduced . RESULTS Three hundred and forty five participants were allocated to the intervention group and compared with 338 controls . At the end of the intervention period the difference in the mean change in systolic blood pressure was 3.31 mm Hg ( 95 % CI 6.32 , 0.29 ; p = 0.03 ) comparing with the control group . In diastolic blood pressure the difference was 3.67 ( 95 % CI 5.22 , 2.12 ; p total cost of the intervention was 101 901.66 pesos . The intervention cost per patient was 34.61 pesos ( US$ 3.78 ) , ( CI 95 % 34.44 , 35.46 ) . The cost-effectiveness ratios was 10.46 pesos ( US$ 1.14 ) for systolic ( CI 95 % 129.31 , 5.51 ) and 9.43 ( US$ 1.03 ) for diastolic ( CI 95 % 19.90 , 2.49 ) . CONCLUSIONS The reduction in blood pressure obtained may well justify the small incremental cost of the intervention", "A r and omized controlled trial was carried out for 1 y in three tertiary and teaching hospitals , in Addis Ababa ( Ethiopia ) , Yogyakarta ( Indonesia ) and Merida ( Mexico ) , to study the effectiveness , feasibility , acceptability and cost of kangaroo mother care ( KMC ) when compared to conventional methods of care ( CMC ) . About 29 % of 649 low birthweight infants ( LBWI ; 1000‐1999 g ) died before eligibility . Of the survivors , 38 % were excluded for various reasons , 149 were r and omly assigned to KMC ( almost exclusive skin‐to‐skin care after stabilization ) , and 136 to CMC ( warm room or incubator care ) . There were three deaths in each group and no difference in the incidence of severe disease . Hypothermia was significantly less common in KMC infants in Merida ( 13.5 vs 31.5 episodes/100 infants/d ) and overall ( 10.8 vs 14.6 ) . Exclusive breastfeeding at discharge was more common in KMC infants in Merida ( 80 % vs 16 % ) and overall ( 88 % vs 70 % ) . KMC infants had a higher mean daily weight gain ( 21.3 g vs 17.7 g ) and were discharged earlier ( 13.4 vs 16.3 d after enrolment ) . KMC was considered feasible and presented advantages over CMC in terms of maintenance of equipment . Mothers expressed a clear preference for KMC and health workers found it safe and convenient . KMC was cheaper than CMC in terms of salaries ( US$ 11 788 vs US$ 29 888 ) and other running costs ( US$ 7501 vs US$ 9876 ) . This study confirms that hospital KMC for stabilized LBWI 1000‐1999 g is at least as effective and safe as CMC , and shows that it is feasible in different setting s , acceptable to mothers of different cultures , and less expensive . Where exclusive breastfeeding is uncommon among LBWI , KMC may bring about an increase in its prevalence and duration , with consequent benefits for health and growth . For hospitals in low‐income countries KMC may represent an appropriate use of scarce re sources", "BACKGROUND Second generation cephalosporins ( CFPs ) are more active in the treatment of acute pyelonephritis during pregnancy but their cost is considerably higher than their predecessors . Cefuroxime , a second generation CFP with oral and parenteral presentations , might offer significant advantages and become a first choice antimicrobial in this setting . AIM To compare the efficacy , safety and cost of cefuroxime and cephradine in the treatment of acute pyelonephritis in pregnancy . PATIENTS AND METHODS Hospitalized women with 12 to 34 weeks of pregnancy , with clinical and bacteriological diagnosis of acute pyelonephritis , were r and omly assigned to receive cefuroxime ( Curocef(r ) , Glaxo Wellcome ) 750 mg t.i.d , i.v . or cephradine 1 g q.i.d . , i.v . If the isolated organism was resistant to the assigned drug the patient was excluded . Once patients were afebrile , they were switched to an oral form of the same antimicrobial . They were discharged according to the clinical status and treated for a total of 14 days . laboratory tests , including urine culture were requested during controls and at the end of follow-up at 28 days . RESULTS One hundred and one patients were r and omized : 49 to receive cephradine and 52 to receive cefuroxime . Patients in the cefuroxime group he d fewer febrile days ( mean 1.7 vs 2.2 , p clinical recovery ( mean 2.7 vs 3.1 days , p rate of bacteriological cure at 28 days ( 78.8 % and 59.2 % , p rate of failure ( 21.2 % vs 40.8 % p rate of resistance of isolated uropathogens was 14 % to cephradine and 1 % to cefuroxime . CONCLUSIONS Cefuroxime can be considered as a first choice option in the treatment of acute pyelonephritis during pregnancy due to its tolerance , microbiological activity and efficacy", "OBJECTIVE To assess the cost-effectiveness ratio of ceftriaxone and cefotaxime to treat moderate to severe community acquired pneumonia ( CAP ) . METHODS A clinical trial was done in five hospitals of the Instituto Mexicano del Seguro Social , at the metropolitan area of Mexico City . Ceftriaxone and cefotaxime were compared to treat moderate to severe CAP , and the costs of purchasing , preparation , administration , hospitalization , and therapeutic success were quantified . Cost-effectiveness ratio was calculated , and sensitivity analysis and incremental analysis were done . RESULTS The main isolated germs were Streptococcus pneumoniae ( 23.6 % ) and Staphylococcus aureus ( 18.5 % ) . Most of the microorganisms were sensitive to ceftriaxone , ceftazidime , and cefotaxime , and were resistant to penicillin , ampicillin , and erythromycin . Therapeutic success was 98 % in the ceftriaxone group and 83 % in the cefotaxime group ( p = 0.0091 ) . Cost-effectiveness ratio for per cent unit of success was $ 19,458.62 Mexican pesos in the ceftriaxone group and $ 29,218.08 in the cefotaxime group . Sensitivity analysis showed consistently a lower cost-effectiveness ratio in the ceftriaxone group . Incremental analysis based on the treatment of 55 patients showed that using ceftriaxone instead of cefotaxime result ed in saving $ 35,170.79 per each additional cured patient . CONCLUSIONS Ceftriaxone has a lower cost-effectiveness ratio than cefotaxime to treat patients with CAP and bad prognosis criteria requiring hospitalization", " Twenty-four patients with acute visceral leishmaniasis and leukopenia ( placebo-controlled trial . Patients received granulocyte-macrophage colony-stimulating factor ( GM-CSF ) , 5 micrograms/kg daily , or placebo for 10 days , plus 10 - 20 mg/kg pentavalent antimony daily for 20 days . In GM-CSF recipients , neutrophil counts increased threefold and fourfold over baseline at 5 and 10 days , respectively , and were significantly higher than those in placebo recipients ( P Eosinophil and monocyte counts were significantly increase in GM-CSF recipients at 10 days ( P Secondary infections occurred in 3 GM-CSF and in 8 placebo recipients ( P = .04 ) . All patients had complete resolution of their leishmaniasis at 3 months . Few adverse events were recorded . GM-CSF , 5 micrograms/kg daily for 10 days , was safe , rapidly reversed neutropenia , and reduced the number of secondary infections in patients with leishmaniasis", "BACKGROUND We undertook a multicentre r and omised controlled trial that compared the st and ard model of antenatal care with a new model that emphasises actions known to be effective in improving maternal or neonatal outcomes and has fewer clinic visits . METHODS Clinics in Argentina , Cuba , Saudi Arabia , and Thail and were r and omly allocated to provide either the new model ( 27 clinics ) or the st and ard model currently in use ( 26 clinics ) . All women presenting for antenatal care at these clinics over an average of 18 months were enrolled . Women enrolled in clinics offering the new model were classified on the basis of history of obstetric and clinical conditions . Those who did not require further specific assessment or treatment were offered the basic component of the new model , and those deemed at higher risk received the usual care for their conditions ; however , all were included in the new-model group for the analyses , which were by intention to treat . The primary outcomes were low birthweight ( There was an assessment of quality of care and an economic evaluation . FINDINGS Women attending clinics assigned the new model ( n=12568 ) had a median of five visits compared with eight within the st and ard model ( n=11958 ) . More women in the new model than in the st and ard model were referred to higher levels of care ( 13.4 % vs 7.3 % ) , but rates of hospital admission , diagnosis , and length of stay were similar . The groups had similar rates of low birthweight ( new model 7.68 % vs st and ard model 7.14 % ; stratified rate difference 0.96 [ 95 % CI -0.01 to 1.92 ] ) , postpartum anaemia ( 7.59 % vs 8.67 % ; 0.32 ) , and urinary-tract infection ( 5.95 % vs 7.41 % ; -0.42 [ -1.65 to 0.80 ] ) . For pre-eclampsia/eclampsia the rate was slightly higher in the new model ( 1.69 % vs 1.38 % ; 0.21 [ -0.25 to 0.67 ] ) . Adjustment by several confounding variables did not modify this pattern . There were negligible differences between groups for several secondary outcomes . Women and providers in both groups were , in general , satisfied with the care received , although some women assigned the new model expressed concern about the timing of visits . There was no cost increase , and in some setting s the new model decreased cost . INTERPRETATIONS Provision of routine antenatal care by the new model seems not to affect maternal and perinatal outcomes . It could be implemented without major resistance from women and providers and may reduce cost", "Between August 1994 and June 1999 , 56 patients were prospect ively r and omized to receive ifosfamide 10 g/m2 + GM-CSF 5 μg/kg/day ( IFO+GM-CSF n = 28 ) and cyclophosphamide 4 g/m2 + GM-CSF 5 μg/kg/day ( CY+GM-CSF n = 28 ) . Both groups were comparable for age , gender , diagnosis , disease stage and previous chemotherapy . The IFO+GM-CSF group demonstrated a shorter median interval between therapy and apheresis ( 10 days ( 8–14 ) vs 13 days ( 8–25 ) P = 0.002 ) , median number of doses of GM-CSF ( 9 ( 7–13 ) vs 15 ( 9–31 ) P = 0.001 ) , median of days with aplasia ( 0.5 ( 0–10 ) vs 6 ( 0–21 ) P = 0.001 ) , median days with fever ( 0 ( 0–6 ) vs 3 ( 0–9 ) P = 0.006 ) and median of days using i.v . antibiotics ( 0 ( 0–11 ) vs 7.5 ( 0–19 ) P = 0.002 ) . The median MNC yield was similar in both groups . The CD34 + cell yield was better in the CY+GM-CSF group ( 3.14 ( 0.9–11.8 ) vs 5.33 ( 0.08–32 ) ) but not at significant levels ( P = 0.1 ) . White blood cell hematopoietic recovery was more rapid in the CY+GM-CSF group ( 16 ( 10–22 ) vs13 ( 10–24 ) P = 0.02 ) . Platelet engraftment was similar in both groups . Costs of mobilization and transplantation were almost the same : $ 28 570 ( $ 18 527–$47 028 ) and $ 30 020 ( $ 17 281–$67 591 ) , respectively ( P = 0.9 ) . There were no differences in disease-free survival and overall survival between both groups . Mild and transient non-hematological toxicity ( hemorrhagic cystitis , decrease in serum creatinine clearance and CNS dysfunction ) was seen most frequently in the IFO+GM-CSF group . Bone Marrow Transplantation ( 2000 ) 25 , 1141–1146", "BACKGROUND One-year follow-up data from the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events ( ESSENCE ) trial show that use of low-molecular-weight heparin ( enoxaparin ) compared with unfractionated heparin in patients hospitalized with unstable angina or non-Q-wave myocardial infa rct ion is associated with a 10 % reduction in the cumulative 1-year risk of death , myocardial infa rct ion , or recurrent angina . Given the higher acquisition cost of enoxaparin relative to unfractionated heparin , we assessed whether the reduced use of revascularization procedures and related care makes enoxaparin a cost-saving therapy in Canada . METHODS AND RESULTS We analyzed cumulative 1-year re source use data on the 1259 ESSENCE patients enrolled in Canadian centers ( 40 % of the total ESSENCE sample ) . Patient-specific data on use of drugs , diagnostic cardiac catheterization , percutaneous transluminal coronary angioplasty , coronary artery bypass grafting , and hospital days were available from the initial hospital stay and cumulative to 1 year . Hospital re sources were costed with the use of data from a teaching hospital in southern Ontario that is a participant in the Ontario Case Costing Project . During the initial hospital stay , use of enoxaparin was associated with reduced use of diagnostic catheterization and revascularization procedures , with the largest effect being reduced use of percutaneous transluminal coronary angioplasty ( 15.0 % vs 10.6 % ; P = .03 ) . At 1 year , the reduced risk and costs of revascularization more than offset increased drug costs for enoxaparin , producing a cost-saving per patient of $ 1485 ( 95 % confidence interval $ -93 to $ 3167 ; P = .06 ) . Sensitivity analysis with lower hospital per diem costs from a community hospital in Ontario still predicts cost savings of $ 1075 per patient over a period of 1 year . CONCLUSIONS The acquisition and administration cost of enoxaparin is higher than for unfractionated heparin ( $ 101 vs $ 39 ) , but in patients with acute coronary syndrome , the reduced need for hospitalization and revascularization over a period of 1 year more than offsets this initial difference in cost . Evidence from this Canadian sub study of ESSENCE supports the view that enoxaparin is less costly and more effective than unfractionated heparin in this indication", "BACKGROUND Aprotinin and epsilon-aminocaproic acid are routinely used to reduce bleeding during cardiac surgery . The marked difference in average wholesale cost between these two drug therapies ( aprotinin , $ 1,080 vs. epsilon-aminocaproic acid , $ 11 ) has generated significant controversy regarding their relative efficacies and costs . METHODS In a multicenter , r and omized , prospect i ve , blinded trial , patients having repeated cardiac surgery received either a high-dose regimen of aprotinin ( total dose , 6 x 10(6 ) kallikrein inactivator units ) or epsilon-aminocaproic acid ( total dose , 270 mg/kg ) . RESULTS Two hundred four patients were studied . Overall ( data are median [ 25th-75th percentiles ] ) , aprotinin-treated patients had less postoperative thoracic drainage ( 511 ml [ 383 - 805 ml ] vs. 655 ml [ 464 - 1,045 ml ] ; P = 0.016 ) and received fewer platelet transfusions ( 0 [ range , 0 - 1 ] vs. 1 [ range , 0 - 2 ] ; P = 0.036 ) . The surgical field was more likely to be considered free of bleeding in aprotinin-treated patients ( 44 % vs. 26 % ; P = 0.012 ) . No differences , however , were seen in allogeneic erythrocyte transfusions or in the time required for chest closure . Overall , direct and indirect bleeding-related costs were greater in aprotinin- than in epsilon-aminocaproic acid-treated patients ( $ 1,813 [ $ 1,476 - 2,605 ] vs. $ 1,088 [ range , $ 511 - 2,057 ] ; P = 0.0001 ) . This difference in cost per case varied in magnitude among sites but not in direction . CONCLUSIONS Aprotinin was more effective than epsilon-aminocaproic acid at decreasing bleeding and platelet transfusions . Epsilon-aminocaproic acid , however , was the more cost-effective therapy over a broad range of estimates for bleeding-related costs in patients undergoing repeated cardiac surgery . A cost-benefit analysis using the lower cost of half-dose aprotinin ( $ 540 ) still result ed in a significant cost advantage using epsilon-aminocaproic therapy ( P = 0.022 )", "PURPOSE We assessed the cost-effectiveness of routine ureteral stenting after ureteroscopic stone removal . MATERIAL S AND METHODS Of 295 consecutive patients who underwent rigid ureteroscopic stone removal 133 in group 1 and 162 in group 2 were r and omized to receive and not receive a stent , respectively , after the procedure . Operative time , stone size , stone location , success rate , postoperative pain and complications were analyzed in each group . RESULTS There were no statistically significant differences in the 2 groups regarding stone size , stone location , success rate , postoperative pain or complications . However , in group 1 operative time was significantly longer than in group 2 ( chi-square test p = 0.019 ) . The hospital charge per patient when placing and not placing a stent after ureteroscopy for stone removal was $ 9,900.95 and $ 3,661.78 , respectively . The female patients with a stent without a suture required an extra charge for stent removal in the operating room , while no men had a stent with a suture . CONCLUSIONS Routine catheter placement after ureteroscopic stone removal increased operative time and did not seem to improve patient outcome . The cost was 30 % that without a stent", "OBJECTIVE To compare early and late results and costs of outpatient haemorrhoidectomy under local anaesthesia with those of inpatient haemorrhoidectomy . DESIGN Prospect i ve study with historical controls . SETTING University hospital , Brazil . SUBJECTS 51 patients who required haemorrhoidectomy . INTERVENTIONS Outpatient haemorrhoidectomy under local anaesthesia . MAIN OUTCOME MEASURES Early and late results and comparative costs . RESULTS One patient was withdrawn from the study because of hypertension and subsequently lost to follow-up . The remaining 50 patients were discharged a mean of 68 ( 23 ) minutes after operation . Twelve patients complained of severe pain , one had faecal impaction and 2 developed bleeding . One patient developed urinary retention , compared with 18 in the historical group ( p satisfied with their treatment . Late complications did not differ significantly from those observed in the historical group . The estimated hospital costs were US$ 313.6 for outpatient , and US$ 716 for inpatient treatment . CONCLUSION Outpatient haemorrhoidectomy under local anaesthesia was safe and comfortable for most patients , with complication rates comparable to or better than those observed after inpatient treatment and at less than half the cost", "BACKGROUND The objective of this study was to analyze hospitalization costs , morbidity , disability , and mortality in patients with acquired immunodeficiency syndrome ( AIDS ) treated with protease inhibitors ( PI ) . METHODS This is a self-controlled , ambispective study of a total of 581 patients with human immunodeficiency virus (HIV)/AIDS seen at the Hospital de Infectología , Centro Médico La Raza , IMSS , in Mexico City during 1997 . A total of 210 ( 36.14 % ) patients initiated protease inhibitor ( PI ) treatment at the onset of the study . Thirty-eight patients satisfied the inclusion criteria for this study and were analyzed retrospectively during the year prior to PI treatment , and then prospect ively throughout the year on PI treatment . As concerns main outcome measures , financial costs , number of hospitalizations , number of infections , and productivity and laboratory parameters ( CD4(+ ) counts and viral load ) were analyzed during the year prior to PI treatment and then prospect ively during the year on PI prescription . Our hypothesis was that the hospital costs , morbidity , disability , and mortality of patients with AIDS decreased while on PI treatment . RESULTS During the year prior to PI prescription , the 38 patients enrolled in the study were admitted on a total of 59 occasions ( 1.55 hospitalizations/patient ) , whereas during the year on PI therapy , all 38 patients had only seven admissions ( 0.18 hospitalizations/patient ) . Hospitalization costs decreased 35 % when annual PI costs for the 38 patients studied were taken into account . The number of microorganisms detected during hospitalization decreased from 24 prior to PI to five on PI . The number of disability days involved in patients on PI decreased significantly ( p died during the year of follow-up under PI treatment . Mortality decreased significantly , from 116/481 ( 23.2 % ) in 1996 , to 77/581 ( 13.2 % ) in 1997 , to 40/740 ( 6.4 % ) in 1998 . There were no deaths among the 38 patients studied during the 1-year follow-up period ; when the observation period was extended 1 additional year , only one patient died ( 2.63 % ) . Only six ( 3.48 % ) of the 172 PI-treated patients with AIDS not included in the study died during the same period . CD4(+ ) cell counts increased from 190.56 + /- 169.5 cells/mm(3 ) to 235.00 + /- 112.65 cells/mm(3 ) ( p Viral loads decreased from 5 logs to 2.4 logs at 12 months of PI treatment ( p patients with AIDS was associated with a lower rate of hospital admissions , lower costs , and a lesser number of infections/year , disabilities , and mortalities . Increase of CD4(+ ) cell counts and decrease in viral loads in the 38 patients were associated with decreased morbility and mortality", "BACKGROUND Strains of Helicobacter pylori that express the CagA protein are associated with a threefold increased gastric cancer risk as compared to H. pylori strains that do not express CagA. Screening and treatment only for CagA antibodies should target those individuals at highest gastric cancer risk while reducing the number of patients requiring antibiotics . We compared the costs and benefits of screening asymptomatic 50-year-old individuals for CagA , screening for all H. pylori strains , and no screening , both in the United States and abroad . MATERIAL S AND METHODS We employed Markov cost-effectiveness analysis using data from r and omized , case-control , and cohort studies . RESULTS In the United States , CagA screening would result in 1.5 million fewer antibiotic treatments but would prevent 1,400 fewer gastric cancers than would screening for all H. pylori . The incremental cost-effectiveness of CagA screening is $ 23,900 per life-year gained ; for H. pylori screening , it is $ 25,100 . Screening in countries with epidemiological characteristics similar to those of Colombia , Finl and , and Japan costs less than $ 5,000 per life-year gained , and the difference between CagA and H. pylori screening is smaller than that in the United States . CONCLUSIONS Screening only for CagA-positive H. pylori is not substantially better than is screening for all H. pylori , either in the United States nor abroad . Screening is substantially more cost-effective outside the United States . Whether population screening is justified , however , is uncertain pending conclusive data regarding the reduction in gastric cancer risk from antibiotics", "BACKGROUND The multicentre , r and omised Benestent-II study investigated a strategy of implantation of a heparin-coated Palmar-Schatz stent plus antiplatelet drugs compared with the use of balloon angioplasty in selected patients with stable or stabilised unstable angina , with one or more de-novo lesions , less than 18 mm long , in vessels of diameter 3 mm or more . METHODS 827 patients were r and omly assigned stent implantation ( 414 patients ) or st and ard balloon angioplasty ( 413 patients ) . The primary clinical endpoint was event-free survival at 6 months , including death , myocardial infa rct ion , and the need for revascularisation . The secondary endpoints were the restenosis rate at 6 months and the cost-effectiveness at 12 months . There was also one-to-one subr and omisation to either clinical and angiographic follow-up or clinical follow-up alone . Analyses were by intention to treat . FINDINGS Four patients ( one stent group , three angioplasty group ) were excluded from analysis since no lesion was found . At 6 months , a primary clinical endpoint had occurred in 53 ( 12.8 % ) of 413 patients in the stent group and 79 ( 19.3 % ) of 410 in the angioplasty group ( p=0.013 ) . This significant difference in clinical outcome was maintained at 12 months . In the subgroup assigned angiographic follow-up , the mean minimum lumen diameter was greater in the stent group than in the balloon-angioplasty group , ( 1.89 [ SD 0.65 ] vs 1.66 [ 0.57 ] mm , p=0.0002 ) , which corresponds to restenosis rates ( diameter stenosis > or = 50 % ) of 16 % and 31 % ( p=0.0008 ) . In the group assigned clinical follow-up alone , event-free survival rate at 12 months was higher in the stent group than the balloon-angioplasty group ( 0.89 vs 0.79 , p=0.004 ) at a cost of an additional 2085 Dutch guilders ( US$ 1020 ) per patient . INTERPRETATION Over 12-month follow-up , a strategy of elective stenting with heparin-coated stents is more effective but also more costly than balloon angioplasty", "OBJECTIVES The purpose of this study was to report the 3-year follow-up results of the ERACI trial ( Argentine R and omized Trial of Percutaneous Transluminal Coronary Angioplasty Versus Coronary Artery Bypass Surgery in Multivessel Disease ) . BACKGROUND Although coronary angioplasty has been used with increased frequency in patients with multivessel coronary artery disease , its value , compared with bypass graft surgery , has not been established . Thus , controlled , r and omized clinical trials such as the ERACI are needed . METHODS In this trial 127 patients who had multivessel coronary artery disease and clinical indication of myocardial revascularization were r and omized to undergo coronary angioplasty ( n = 63 ) or bypass surgery ( n = 64 ) . The primary end point of this study was event-free survival ( survival with freedom from myocardial infa rct ion , angina and new revascularization procedures ) for both groups of patients at 1 , 3 and 5 years of follow-up . RESULTS Freedom from combined cardiac events ( death , Q-wave myocardial infa rct ion , angina and repeat revascularization procedures ) was significantly greater for the bypass surgery group than the coronary angioplasty group ( 77 % vs. 47 % ; p mortality or in the frequency of myocardial infa rct ion ( 7.8 % vs. 7.8 % ; p = 0.8 ) between the two groups . However , patients who had bypass surgery were more frequently free of angina ( 79 % vs. 57 % ; p additional re interventions ( 6.3 % vs. 37 % ; p coronary angioplasty . CONCLUSIONS 1 ) Freedom from combined cardiac events at 3-year follow-up was greater in patients who had bypass surgery than in those who had coronary angioplasty . 2 ) The coronary angioplasty group had a higher incidence of recurrence of angina and the need for repeat revascularization procedures . 3 ) Cumulative cost at 3-year follow-up was greater for the bypass surgery group than for the coronary angioplasty group", "Background —Coronary stenting improves outcomes compared with balloon angioplasty , but it is costly and may have other disadvantages . Limiting stent use to patients with a suboptimal result after angioplasty ( provisional angioplasty ) may be as effective and less expensive . Methods and Results —To analyze the cost-effectiveness of provisional angioplasty , patients scheduled for single-vessel angioplasty were first r and omized to receive primary stenting ( 97 patients ) or balloon angioplasty guided by Doppler flow velocity and angiography ( 523 patients ) . Patients in the latter group were further r and omized after optimization to either additional stenting or termination of the procedure to further investigate what is “ optimal . ” An optimal result was defined as a flow reserve > 2.5 and a diameter stenosis stenting was needed in 129 patients ( 25 % ) who were r and omized to balloon angioplasty , and an optimal result was obtained in 184 of the 523 patients ( 35 % ) . There was no significant difference in event-free survival at 1 year between primary stenting ( 86.6 % ) and provisional angioplasty ( 85.6 % ) . Costs after 1 year were significantly higher for provisional angioplasty ( EUR 6573 versus EUR 5885;P = 0.014 ) . Results after the second r and omization showed that stenting was also more effective after optimal balloon angioplasty ( 1-year event free survival , 93.5 % versus 84.1%;P = 0.066 ) . Conclusions —After 1 year of follow-up , provisional angioplasty was more expensive and without clinical benefit . The beneficial value of stenting is not limited to patients with a suboptimal result after balloon angioplasty", "The Losartan Heart Failure ELITE Study recently found that in patients with symptomatic heart failure and a left ventricular ejection fraction of ≤0.40 , losartan compared to captopril improved survival with better tolerability . The objective of this study was to perform an economic evaluation of losartan versus captopril based on the results of the Losartan Heart Failure ELITE Study . The Losartan Heart Failure ELITE Study was a multinational , double-blind , r and omized 48-week study comparing the safety and efficacy of losartan to captopril in angiotensin-converting enzyme-inhibitor-naive patients ≥65 years with symptomatic heart failure . Data on health care re source utilization were collected as part of the trial . We conducted a cost-effectiveness analysis to estimate the lifetime benefits of treatment and the associated costs . We observed no differences between treatments in the number of hospitalizations , hospital days , and emergency room visits per patient over the trial period . We estimated the total cost of losartan to be USD 54 ( 95 % CI : USD –1,717 , USD 1,755 ) less per patient than captopril over this time frame . We also estimated that over the projected remaining lifetime of the study population , losartan compared to captopril would increase survival by 0.20 years ( undiscounted ) at an average cost of USD 769 ( discounted ) more per patient . This cost increase translated into a cost-effectiveness ratio of USD 4,047 per year of life gained for losartan relative to captopril . In patients with symptomatic heart failure , losartan compared to captopril increased survival with better tolerability at a cost well within the range accepted as cost-effective", "OBJECTIVE This study sought to compare two strategies of revascularization in patients obtaining a good immediate angiographic result after percutaneous transluminal coronary angioplasty ( PTCA ) : elective stenting versus optimal PTCA . A good immediate angiographic result with provisional stenting was considered to occur only if early loss in minimal luminal diameter ( MLD ) was documented at 30 min post-PTCA angiography . BACKGROUND Coronary stenting reduces restenosis in lesions exhibiting early deterioration ( > 0.3 mm ) in MLD within the first 24 hours ( early loss ) after successful PTCA . Lesions with no early loss after PTCA have a low restenosis rate . METHODS To compare angiographic restenosis and target vessel revascularization ( TVR ) of lesions treated with coronary stenting versus those treated with optimal PTCA , 116 patients were r and omized to stent ( n=57 ) or to optimal PTCA ( n=59 ) . After r and omization in the PTCA group , 13.5 % of the patients crossed over to stent due to early loss ( provisional stenting ) . RESULTS Baseline demographic and angiographic characteristics were similar in both groups of patients . At 7.6 months , 96.6 % of the entire population had a follow-up angiographic study : 98.2 % in the stent and 94.9 % in the PTCA group . Immediate and follow-up angiographic data showed that acute gain was significantly higher in the stent than in the PTCA group ( 1.95 vs. 1.5 mm ; p late loss was significantly higher in the stent than the PTCA group ( 0.63+/-0.59 vs. 0.26+/-0.44 , respectively ; p=0.01 ) . Hence , net gain with both techniques was similar ( 1.32 Angiographic restenosis rate at follow-up ( 19.2 % in stent vs. 16.4 % in PTCA ; p = NS ) and TVR ( 17.5 % in stent vs. 13.5 % in PTCA ; p = NS ) were similar . Furthermore , event-free survival was 80.8 % in the stent versus 83.1 % in the PTCA group ( p = NS ) . Overall costs ( hospital and follow-up ) were US $ 591,740 in the stent versus US $ 398,480 in the PTCA group ( p restenosis rate and TVR , but lower cost than primary stenting after PTCA", "Advances in immunosuppressive therapy have substantially improved one-year clinical outcomes for renal transplantation.1 However , acute rejection still occurs in up to 50 % of kidney transplantation recipients during the first year,2 and it remains the major contributor to chronic rejection and long-term graft failure . [ 3 ] , [ 4 ] and [ 5 ] Although episodes of acute rejection are reversible with heightened doses of steroids and antibody therapy , the implication s for increased healthcare costs and poor long-term outcome underscore the importance of developing therapies to reduce acute rejection . Basiliximab ( Simulect , Novartis , Basel , Switzerl and ) is a high-affinity chimeric antiinterleukin-2 receptor monoclonal antibody that is indicated for the prophylaxis of acute rejection after renal transplantation . [ 6 ] and [ 7 ] R and omised clinical trials have demonstrated that basiliximab is highly effective in suppressing acute rejection when used in combination with dual therapy of cyclosporin and steroids . [ 8 ] and [ 9 ] Recently , a phase III international multi-centre trial was performed to evaluate the effectiveness of basiliximab in renal transplantation patients receiving a st and ard triple therapy regimen of cyclosporin , steroids , and azathioprine.10 An economic evaluation of the trial was undertaken alongside the clinical studies . We determined the economic impact of adding basiliximab to triple therapy . Our objectives were to compare within-trial re source use between basiliximab-treated and placebo-treated patients within six months of renal transplantation and to evaluate the cost implication s of basiliximab use , relative to clinical outcomes", "INTRODUCTION In most developed countries vacuum aspiration has been shown to be safer and less costly than sharp curettage ( SC ) for uterine evacuation . In many of the developing countries , including Brazil , sharp curettage ( SC ) is the most commonly used technique for treating cases of incomplete abortion admitted to hospital . The procedure often involves light to heavy sedation for pain control and an overnight hospital stay for patient recuperation and monitoring . Two hypotheses are examined : the first , that the use of manual vacuum aspiration (MVA)--a variation of the vacuum aspiration , would be less costly than SC for the treatment of cases of incomplete abortion admitted to hospital ; and the second , that the treatment of incomplete abortion with MVA would substantially reduce the length of hospital stay . METHODOLOGY Thirty women with diagnosis of first trimester incomplete abortion were r and omly allocated to the SC or MVA group . Rapid- assessment data collection techniques were used to identify factors that contributed to cost reduction and hospital stay . RESULTS AND CONCLUSION The results of the study show that , overall , patients treated for incomplete abortion with MVA spent 77 % less time in the hospital and consumed 41 % fewer re sources than similarly diagnosed patients treated with SC . Recommendations are made as to the need of certain changes in patient management . Particularly necessary is information regarding cultural perception and concepts of abortion treatment" ]	4118988e-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Bariatric surgery has emerged as a competitive strategy for obese patients . However , its comparative efficacy against non-surgical treatments remains ill-defined , especially among nonseverely obese crowds . Therefore , we implemented a systematic review and meta- analysis in order for an academic addition to current literature s. METHODS Literature s were retrieved from data bases of PubMed , Web of Science , EMBASE and Cochrane Library . R and omized trials comparing surgical with non-surgical therapies for obesity were included . A Revised Jadad 's Scale and Risk of Bias Summary were employed for method ological assessment . Subgroups analysis , sensitivity analysis and publication bias assessment were respectively performed in order to find out the source of heterogeneity , detect the outcome stability and potential publication bias . RESULTS 25 r and omized trials were eligibly included , totally comprising of 1194 participants . Both groups displayed well comparability concerning baseline parameters ( P > 0.05 ) . The pooled results of primary endpoints ( weight loss and diabetic remission ) revealed a significant advantage among surgical patients rather than those receiving non-surgical treatments ( P cardiovascular indicators , bariatric surgery was superior to conventional arms in terms of metabolic secondary parameters ( P Bariatric surgery is a better therapeutic option for weight loss , irrespective of follow-up duration , surgical techniques and obesity levels	[ "Improvement in type 2 diabetes after Roux-en-Y gastric bypass ( RYGB ) has been attributed partly to weight loss , but mechanisms beyond weight loss remain unclear . We performed an ancillary study to the Diabetes Surgery Study to assess changes in incretins , insulin sensitivity , and secretion 1 year after r and omization to lifestyle modification and intensive medical management ( LS/IMM ) alone ( n = 34 ) or in conjunction with RYGB ( n = 34 ) . The RYGB group lost more weight and had greater improvement in HbA1c . Fasting glucose was lower after RYGB than after LS/IMM , although the glucose area under the curve decreased comparably for both groups . Insulin sensitivity increased in both groups . Insulin secretion was unchanged after LS/IMM but decreased after RYGB , except for a rapid increase during the first 30 min after meal ingestion . Glucagon-like peptide 1 ( GLP-1 ) was substantially increased after RYGB , while gastric inhibitory polypeptide and glucagon decreased . Lower HbA1c was most strongly correlated with the percentage of weight loss for both groups . At baseline , a greater C-peptide index and 90-min postpr and ial C-peptide level were predictive of lower HbA1c at 1 year after RYGB . β-Cell glucose sensitivity , which improved only after RYGB , and improved disposition index were associated with lower HbA1c in both groups , independent of weight loss . Weight loss and preserved β-cell function both predominantly determine the greatest glycemic benefit after RYGB", "Objective : To compare bariatric surgery versus intensive medical weight management ( MWM ) in patients with type 2 diabetes mellitus ( T2DM ) who do not meet current National Institutes of Health criteria for bariatric surgery and to assess whether the soluble form of receptor for advanced glycation end products ( sRAGE ) is a biomarker to identify patients most likely to benefit from surgery . Background : There are few studies comparing surgery to MWM for patients with T2DM and BMI less than 35 . Methods : Fifty-seven patients with T2DM and BMI 30 to 35 , who otherwise met the criteria for bariatric surgery were r and omized to MWM versus surgery ( bypass , sleeve or b and , based on patient preference ) . The primary outcomes assessed at 6 months were change in homeostatic model of insulin resistance ( HOMA-IR ) and diabetes remission . Secondary outcomes included changes in HbA1c , weight , and sRAGE . Results : The surgery group had improved HOMA-IR ( −4.6 vs + 1.6 ; P = 0.0004 ) and higher diabetes remission ( 65 % vs 0 % , P lower HbA1c ( 6.2 vs 7.8 , P = 0.002 ) , lower fasting glucose ( 99.5 vs 157 ; P = 0.0068 ) , and fewer T2DM medication requirements ( 20 % vs 88 % ; P lost more weight ( 7 . vs 1.0 BMI decrease , P baseline sRAGE was associated with better weight loss outcomes ( r = −0.641 ; P = 0.046 ) . There were no mortalities . Conclusions : Surgery was very effective short-term in patients with T2DM and BMI 30 to 35 . Baseline sRAGE may predict patients most likely to benefit from surgery . These findings need to be confirmed with larger studies . Clinical Trials.gov ID :", "CONTEXT Obstructive sleep apnea ( OSA ) is strongly related to obesity . Weight loss is recommended as part of the overall management plan for obese patients diagnosed with OSA . OBJECTIVE To determine whether surgically induced weight loss is more effective than conventional weight loss therapy in the management of OSA . DESIGN , SETTING , AND PATIENTS A r and omized controlled trial of 60 obese patients ( body mass index : > 35 and These patients had been prescribed continuous positive airway pressure ( CPAP ) therapy to manage OSA and were identified via accredited community sleep clinics . The trial was conducted between September 2006 and March 2009 by university- and teaching hospital-based clinical research ers in Melbourne , Australia . Patients with obesity hypoventilation syndrome , previous bariatric surgery , contraindications to bariatric surgery , or significant cardiopulmonary , neurological , vascular , gastrointestinal , or neoplastic disease were excluded . INTERVENTIONS Patients were r and omized to a conventional weight loss program that included regular consultations with a dietitian and physician , and the use of very low-calorie diets as necessary ( n = 30 ) or to bariatric surgery ( laparoscopic adjustable gastric b and ing ; n = 30 ) . MAIN OUTCOME MEASURES The primary outcome was baseline to 2-year change in AHI on diagnostic polysomnography scored by staff blinded to r and omization . Secondary outcomes were changes in weight , CPAP adherence , and functional status . RESULTS Patients lost a mean of 5.1 kg ( 95 % CI , 0.8 to 9.3 kg ) in the conventional weight loss program compared with 27.8 kg ( 95 % CI , 20.9 to 34.7 kg ) in the bariatric surgery group ( P AHI decreased by 14.0 events/hour ( 95 % CI , 3.3 to 24.6 events/hour ) in the conventional weight loss group and by 25.5 events/hour ( 95 % CI , 14.2 to 36.7 events/hour ) in the bariatric surgery group . The between-group difference was -11.5 events/hour ( 95 % CI , -28.3 to 5.3 events/hour ; P = .18 ) . CPAP adherence did not differ between the groups . The bariatric surgery group had greater improvement in the Short Form 36 physical component summary score ( mean , 9.3 [ 95 % CI , 0.5 to 18.0 ] ; P = .04 ) . CONCLUSION Among a group of obese patients with OSA , the use of bariatric surgery compared with conventional weight loss therapy did not result in a statistically greater reduction in AHI despite major differences in weight loss . TRIAL REGISTRATION anzctr.org Identifier : 12605000161628", "CONTEXT Observational studies suggest that surgically induced loss of weight may be effective therapy for type 2 diabetes . OBJECTIVE To determine if surgically induced weight loss results in better glycemic control and less need for diabetes medications than conventional approaches to weight loss and diabetes control . DESIGN , SETTING , AND PARTICIPANTS Unblinded r and omized controlled trial conducted from December 2002 through December 2006 at the University Obesity Research Center in Australia , with general community recruitment to established treatment programs . Participants were 60 obese patients ( BMI > 30 and INTERVENTIONS Conventional diabetes therapy with a focus on weight loss by lifestyle change vs laparoscopic adjustable gastric b and ing with conventional diabetes care . MAIN OUTCOME MEASURES Remission of type 2 diabetes ( fasting glucose level glycated hemoglobin [ HbA1c ] value weight and components of the metabolic syndrome . Analysis was by intention-to-treat . RESULTS Of the 60 patients enrolled , 55 ( 92 % ) completed the 2-year follow-up . Remission of type 2 diabetes was achieved by 22 ( 73 % ) in the surgical group and 4 ( 13 % ) in the conventional-therapy group . Relative risk of remission for the surgical group was 5.5 ( 95 % confidence interval , 2.2 - 14.0 ) . Surgical and conventional-therapy groups lost a mean ( SD ) of 20.7 % ( 8.6 % ) and 1.7 % ( 5.2 % ) of weight , respectively , at 2 years ( P Remission of type 2 diabetes was related to weight loss ( R2 = 0.46 , P lower baseline HbA1c levels ( combined R2 = 0.52 , P no serious complications in either group . CONCLUSIONS Participants r and omized to surgical therapy were more likely to achieve remission of type 2 diabetes through greater weight loss . These results need to be confirmed in a larger , more diverse population and have long-term efficacy assessed . TRIAL REGISTRATION actr.org Identifier : ACTRN012605000159651", "Objective : Roux-en-Y gastric bypass ( RYGB ) produces more durable glycemic control than sleeve gastrectomy ( SG ) or intensive medical therapy ( IMT ) . However , the contribution of acylated ghrelin ( AG ) , a gluco-regulatory/appetite hormone , to improve glucose metabolism and body composition in patients with type 2 diabetes ( T2D ) following RYGB is unknown . Design : STAMPEDE ( Surgical Treatment and Medication Potentially Eradicate Diabetes Efficiently ) was a prospect i ve , r and omized controlled trial . Subjects : Fifty-three ( body mass index : 36±3 kg m−2 , age : 49±9 years ) poorly controlled patients with T2D ( HbA1c ( glycated hemoglobin ) : 9.7±2 % ) were r and omized to IMT , IMT+RYGB or IMT+SG and underwent a mixed-meal tolerance test at baseline , 12 , and 24 months for evaluation of AG suppression ( postpr and ial minus fasting ) and beta-cell function ( oral disposition index ; glucose-stimulated insulin secretion × Matsuda index ) . Total/ and roid body fat ( dual-energy X-ray absorptiometry ) was also assessed . Results : RYGB and SG reduced body fat comparably ( 15–23 kg ) at 12 and 24 months , whereas IMT had no effect . Beta-cell function increased 5.8-fold in RYGB and was greater than IMT at 24 months ( P difference in insulin secretion between SG vs IMT at 24 months ( P=0.32 ) . Fasting AG was reduced fourfold following SG ( P months . AG suppression improved more following RYGB than SG or IMT at 24 months ( P=0.01 vs SG , P=0.07 vs IMT ) . At 24 months , AG suppression was associated with increased postpr and ial glucagon-like peptide-1 ( r=−0.32 , P Enhanced AG suppression persists for up to 2 years after RYGB , and this effect is associated with decreased and roid obesity and improved insulin secretion . Together , these findings suggest that AG suppression is partly responsible for the improved glucose control after RYGB surgery", "Bariatric surgery is currently the most effective therapy to induce weight loss in morbidly obese patients . Objective . This controlled , clinical trial with a two-year intervention was aim ed at comparing the efficacy of two nonsurgical approaches versus bariatric surgery , on body weight changes and metabolic parameters in morbidly obese patients . Methods . Patients were r and omized to an Intensive Lifestyle Intervention ( ILI ) ( n = 60 ) or Conventional Obesity Therapy ( COT ) ( n = 46 ) . The ILI group received behavioral therapy and nutritional counseling . The COT group received st and ard medical treatment . They were compared with a third group , Surgical Obesity Group ( SOG ) ( n = 37 ) . Results . Patients who received ILI had a greater percentage of weight loss than patients receiving COT ( −11.3 % versus −1.6 % ; p morbidly obese after just six months of intervention , increasing to 44.4 % after 24 months of intervention . The percentage weight loss in SOG was −29.6 % after that same period of time . Conclusions . ILI was associated with significant weight loss when compared to COT , in a group of patients with obesity . An ILI approach could be an alternative therapy to patients with obesity , who are not c and i date s to undergo bariatric surgery . This trial is registered with EudraCT 2009 - 013737 - 24", "Objective This report documents that the gastric bypass operation provides long-term control for obesity and diabetes . Summary Background Data Obesity and diabetes , both notoriously resistant to medical therapy , continue to be two of our most common and serious diseases . Methods Over the last 14 years , 608 morbidly obese patients underwent gastric bypass , an operation that restricts caloric intake by ( 1 ) reducing the functional stomach to approximately 30 mL , ( 2 ) delaying gastric emptying with a c. 0.8 to 1.0 cm gastric outlet , and ( 3 ) excluding foregut with a 40 to 60 cm Roux-en-Y gastrojejunostomy . Even though many of the patients were seriously ill , the operation was performed with a perioperative mortality and complication rate of 1.5 % and 8.5 % , respectively . Seventeen of the 608 patients ( Gastric bypass provides durable weight control . Weights fell from a preoperative mean of 304.4 lb ( range , 198 to 615 lb ) to 192.2 lb ( range , 104 to 466 ) by 1 year and were maintained at 205.4 lb ( range , 107 to 512 lb ) at 5 years , 206.5 lb ( 130 to 388 lb ) at 10 years , and 204.7 lb ( 158 to 270 lb ) at 14 years . The operation provides long-term control of non-insulin-dependent diabetes mellitus ( NIDDM ) . In those patients with adequate follow-up , 121 of 146 patients ( 82.9 % ) with NIDDM and 150 of 152 patients ( 98.7 % ) with glucose impairment maintained normal levels of plasma glucose , glycosylated hemoglobin , and insulin . These antidiabetic effects appear to be due primarily to a reduction in caloric intake , suggesting that insulin resistance is a secondary protective effect rather than the initial lesion . In addition to the control of weight and NIDDM , gastric bypass also corrected or alleviated a number of other comorbidities of obesity , including hypertension , sleep apnea , cardiopulmonary failure , arthritis , and infertility", "The effects of weight loss on erectile function and hormones have not been well studied . The aim of this study was to measure the degree to which sexual function and in particular erectile function and hormonal environment change after substantial weight loss , surgically and non-surgically induced in the morbidly obese male in a prospect i ve r and omized long-term controlled trial . Furthermore , how surgery makes a difference when treating morbidly obese men was envisaged in this context . We prospect ively studied 20 morbidly obese men for 24 months , divided into two groups : group A included 10 patients who underwent life style modifications ( exercise and diet ) for 4 months and subsequently gastric bypass , and another 10 patients in group B were kept on weekly follow-up . None of the men were taking phosphodiesterase type-5 inhibitors . All patients underwent International Index of Erectile Function (IIEF)-5 question naire , serum oestradiol , prolactin ( PRL ) , luteinizing ( LH ) and follicle-stimulating ( FSH ) hormones , free and total testosterone ( FT and TT ) at baseline ( time 0 ) , surgery - 4 months latter baseline ( time 1 ) and final evaluation - 24 months ( time 2 ) . From times 0 to 1 , group A presented a mean body mass index ( BMI ) reduction of 12.6 ( p 0.05 ) . The BMI reductions between times 0 and 2 were 24.7 ( p 0.05 ) for groups A and B respectively . BMI average between the two groups was similar at time 0 ( p = 0.2142 ) , and different at times 1 ( p = 0.0033 ) and 2 ( p Increase in IIEF-5 score ( p = 0.0469 ) , TT ( p = 0.0349 ) and FSH levels ( p = 0.0025 ) , and reduction in PRL level ( p IIEF-5 , TT and FT increased significantly in group A ( p = 0.0224 , 0.0043 and 0.0149 respectively ) . Surgery-induced weight loss increased erectile function quality measured by IIEF-5 question naire , increased TT , FT and FSH and reduced PRL levels . The hormonal impact verified could justify the improvement in erectile function . Lifestyle modifications impacted BMI without hormonal or sexual impact in morbidly obese . New studies are warranted in the field to support our data", "Background Proven short-term effectiveness of obesity therapy should be re-evaluated in the long-term . The objective of this paper is to determine the long-term ( 10 years ) outcome for patients from a r and omised controlled trial ( RCT ) . Methods A RCT in 2002 compared laparoscopic adjustable gastric b and ( LAGB ) for obesity with non-surgical therapy . Follow-up has been conducted at 10 years . Eighty patients ( BMI 30–35 ) were r and omised to a non-surgical or a surgical program . Outcome data are available on 37 ( 92.5 % ) of the surgical patients and 27 ( 62.5 % ) of the non-surgical patients at 10 years . Results Weight change , the metabolic syndrome , quality of life , adverse events and direct costs of the surgical cohort were the main results of the study . A durable weight loss is present in the surgical group with a mean ( SD ) 10-year weight loss of 14.1 ( 7.7 ) kg ( 63.4 % EWL ) , better than the non-surgical group ( mean ( SD ) = 0.4 ( 10.5 ) kg ; p ) . The metabolic syndrome was reduced from 14 to 4 of the 37 patients who completed 10 years within the LAGB groups . Proximal gastric enlargements occurred in 17 ( 30 % ) of the 57 who had LAGB and removal of the b and occurred in 7 ( 12 % ) . The annual maintenance costs including additional surgery was AUD $ 765 per patient per year . Conclusions Bariatric surgery with the LAGB can achieve long-term weight reduction which is better than a program of non-surgical therapy . There is also a sustained reduction of the metabolic syndrome . There is a significant maintenance requirement after LAGB", "AIMS The aim of this study was to evaluate the effect of laparoscopic Roux-en-Y gastric bypass ( RYGB ) surgery compared with usual care with and without Exenatide therapy in obese people with type 2 diabetes mellitus ( T2DM ) and hypertension . METHODS 108 obese T2DM with hypertension were enrolled and r and omly allocated to usual care ( group A ) , usual care plus Exenatide ( group B ) , and RYGB surgery ( group C ) . Demographic characteristics , metabolic parameters and cardiac structure/function along with inflammatory cytokines were measured and compared before and after 12 months . RESULTS At 12 months , diabetes remission had occurred in no patients in groups A and B versus 90 % in group C , and there was a significant decrease in requirement of antihypertensive drugs in group C compared with groups A and B ( P ( body mass index , hemoglobin A1c , homeostasis model assessment of insulin resistance , lipids ) , inflammation index ( high sensitivity C-reactive protein , tumor necrosis factor-α , high molecular weight adiponectin ) and cardiac structure ( left ventricular mass index ) were significantly improved in groups B and C , but patients in group C had the greatest degree of improvement ( P CONCLUSION RYGB surgery improves a number of parameters including cardiovascular function in obese hypertensive people with T2DM . This is likely to be due to , at least in part , an improvement in the abnormal metabolic panel and to reduced inflammation", "One of the main goals of weight reduction in morbidly obese subjects is its benefit on coronary heart disease ( CHD ) risk . A cross-sectional study was design ed to r and omly assign 79 morbidly obese subjects ( 27 men and 52 women ; age : 30 - 45 years ) either to a diet protocol ( 20 kcal per kg fat-free mass ( FFM ) ; 55 % carbohydrates , 30 % fat , and 15 % proteins ) or to malabsorptive surgery ( biliopancreatic diversion ) . Fatness parameters , measured by dual-energy X-ray absorptiometry , lipid profile , insulin , leptin , sex steroid hormones and sex hormone-binding globulin ( SHBG ) levels were compared at baseline and 1 year after the beginning of the study . The data showed that plasma SHBG levels , but not testosterone levels , correlated negatively to fasting insulin levels and positively to HDL-cholesterol in both men and women . Total leptin levels were significantly lower ( P plasma leptin correlated significantly and positively with insulin but negatively with SHBG.A step-down regression analysis showed that FFM and SHBG , but not insulin levels , were the most powerful independent variables for predicting HDL-cholesterol levels in morbidly obese patients . The negative relationship between SHBG levels and CHD risk appears to be mediated by a concomitant variation in body fatness . Finally , in obese patients , SHBG levels seem to be an indicator of total adiposity rather than an index of an altered insulin/glucose homeostasis", "IMPORTANCE Many questions remain unanswered about the role of bariatric surgery for people with type 2 diabetes mellitus ( T2DM ) . OBJECTIVE To determine feasibility of a r and omized clinical trial ( RCT ) and compare initial outcomes of bariatric surgery and a structured weight loss program for treating T2DM in participants with grade s I and II obesity . DESIGN , SETTING , AND PARTICIPANTS A 12-month , 3-arm RCT at a single center including 69 participants aged 25 to 55 years with a body mass index ( calculated as weight in kilograms divided by height in meters squared ) of 30 to 40 and T2DM . INTERVENTIONS Roux-en-Y gastric bypass ( RYGB ) , laparoscopic adjustable gastric b and ing ( LAGB ) , and an intensive lifestyle weight loss intervention ( LWLI ) . MAIN OUTCOMES AND MEASURES Primary outcomes in the intention-to-treat cohort were feasibility and effectiveness measured by weight loss and improvements in glycemic control . RESULTS Of 667 potential participants who underwent screening , 69 ( 10.3 % ) were r and omized . Among the r and omized participants , 30 ( 43 % ) had grade I obesity , and 56 ( 81 % ) were women . Mean ( SD ) age was 47.3 ( 6.4 ) years and hemoglobin A1c level , 7.9 % ( 2.0 % ) . After r and omization , 7 participants ( 10 % ) refused to undergo their allocated intervention ( 3 RYGB , 1 LAGB , and 3 LWLI ) , and 1 RYGB participant was excluded for current smoking . Twenty participants underwent RYGB ; 21 , LAGB ; and 20 , LWLI , with 12-month retention rates of 90 % , 86 % , and 70 % , respectively . In the intention-to-treat cohort with multiple imputation for missing data , RYGB participants had the greatest mean weight loss from baseline ( 27.0 % ; 95 % CI , 30.8 - 23.3 ) compared with LAGB ( 17.3 % ; 95 % CI , 21.1 - 13.5 ) and LWLI ( 10.2 % ; 95 % CI , 14.8 - 5.61 ) ( P Partial and complete remission of T2DM were 50 % and 17 % , respectively , in the RYGB group and 27 % and 23 % , respectively , in the LAGB group ( P remission in the LWLI group . Significant reductions in use of antidiabetics occurred in both surgical groups . No deaths were noted . The 3 serious adverse events included 1 ulcer treated medically in the RYGB group and 2 rehospitalizations for dehydration in the LAGB group . CONCLUSIONS AND RELEVANCE This study highlights several potential challenges to successful completion of a larger RCT for treatment of T2DM and obesity in patients with a body mass index of 30 to 40 , including the difficulties associated with recruiting and r and omizing patients to surgical vs nonsurgical interventions . Preliminary results show that RYGB was the most effective treatment , followed by LAGB for weight loss and T2DM outcomes at 1 year . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01047735", "BACKGROUND Weight loss is associated with short-term amelioration and prevention of metabolic and cardiovascular risk , but whether these benefits persist over time is unknown . METHODS The prospect i ve , controlled Swedish Obese Subjects Study involved obese subjects who underwent gastric surgery and contemporaneously matched , conventionally treated obese control subjects . We now report follow-up data for subjects ( mean age , 48 years ; mean body-mass index , 41 ) who had been enrolled for at least 2 years ( 4047 subjects ) or 10 years ( 1703 subjects ) before the analysis ( January 1 , 2004 ) . The follow-up rate for laboratory examinations was 86.6 percent at 2 years and 74.5 percent at 10 years . RESULTS After two years , the weight had increased by 0.1 percent in the control group and had decreased by 23.4 percent in the surgery group ( P weight had increased by 1.6 percent and decreased by 16.1 percent , respectively ( P Energy intake was lower and the proportion of physically active subjects higher in the surgery group than in the control group throughout the observation period . Two- and 10-year rates of recovery from diabetes , hypertriglyceridemia , low levels of high-density lipoprotein cholesterol , hypertension , and hyperuricemia were more favorable in the surgery group than in the control group , whereas recovery from hypercholesterolemia did not differ between the groups . The surgery group had lower 2- and 10-year incidence rates of diabetes , hypertriglyceridemia , and hyperuricemia than the control group ; differences between the groups in the incidence of hypercholesterolemia and hypertension were undetectable . CONCLUSIONS As compared with conventional therapy , bariatric surgery appears to be a viable option for the treatment of severe obesity , result ing in long-term weight loss , improved lifestyle , and , except for hypercholesterolemia , amelioration in risk factors that were elevated at baseline", "BACKGROUND Bariatric surgery improves glycaemia in obese people with type 2 diabetes , but its effects are uncertain in overweight people with this disease . We aim ed to identify whether laparoscopic adjustable gastric b and surgery can improve glucose control in people with type 2 diabetes who were overweight but not obese . METHODS We did an open-label , parallel-group , r and omised controlled trial between Nov 1 , 2009 , and June 30 , 2013 , at one centre in Melbourne , Australia . Patients aged 18 - 65 years with type 2 diabetes and a BMI between 25 and 30 kg/m2 were r and omly assigned ( 1:1 ) , by computer-generated r and om sequence , to receive either multidisciplinary diabetes care plus laparoscopic adjustable gastric b and surgery or multidisciplinary diabetes care alone . The primary outcome was diabetes remission 2 years after r and omisation , defined as glucose concentrations of less than 7.0 mmol/L when fasting and less than 11.1 mmol/L 2 h after 75 g oral glucose , at least two days after stopping glucose-lowering drugs . Analysis was by intention to treat . This trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12609000286246 . FINDINGS 51 patients were r and omised to the multidisciplinary care plus gastric b and group ( n=25 ) or the multidisciplinary care only group ( n=26 ) , of whom 23 participants and 25 participants , respectively , completed follow-up to 2 years . 12 ( 52 % ) participants in the multidisciplinary care plus gastric b and group and two ( 8 % ) participants in the multidisciplinary care only group achieved diabetes remission ( difference in proportions 0.44 , 95 % CI 0.17 - 0.71 ; p=0.0012 ) . One ( 4 % ) participant in the gastric b and group needed revisional surgery and four others ( 17 % ) had a total of five episodes of food intolerance due to excessive adjustment of the b and . INTERPRETATION When added to multidisciplinary care , laparoscopic adjustable gastric b and surgery for overweight people with type 2 diabetes improves glycaemic control with an acceptable adverse event profile . Laparoscopic adjustable gastric b and surgery is a reasonable treatment option for this population . FUNDING Monash University Centre for Obesity Research and Education and Allergan", "IMPORTANCE Questions remain about the role and durability of bariatric surgery for type 2 diabetes mellitus ( T2DM ) . OBJECTIVE To compare the remission of T2DM following surgical and nonsurgical treatments . DESIGN , SETTING , AND PARTICIPANTS In this 3-arm r and omized clinical trial conducted at the University of Pittsburgh Medical Center from October 1 , 2009 , to June 26 , 2014 , in Pittsburgh , Pennsylvania , outcomes were assessed 3 years after treating 61 obese participants aged 25 to 55 years with T2DM . Analysis was conducted with an intent-to-treat population . INTERVENTIONS Participants were r and omized to either an intensive lifestyle weight loss intervention for 1 year followed by a low-level lifestyle intervention for 2 years or surgical treatments ( Roux-en-Y gastric bypass [ RYGB ] or laparoscopic adjustable gastric b and ing [ LAGB ] ) followed by low-level lifestyle intervention in years 2 and 3 . MAIN OUTCOMES AND MEASURES Primary end points were partial and complete T2DM remission and secondary end points included diabetes medications and weight change . RESULTS Body mass index ( calculated as weight in kilograms divided by height in meters squared ) was less than 35 for 26 participants ( 43 % ) , 50 ( 82 % ) were women , and 13 ( 21 % ) were African American . Mean ( SD ) values were 100.5 ( 13.7 ) kg for weight , 47.3 ( 6.6 ) years for age , 7.8 % ( 1.9 % ) for hemoglobin A1c level , and 171.3 ( 72.5 ) mg/dL for fasting plasma glucose level . Partial or complete T2DM remission was achieved by 40 % ( n = 8) of RYGB , 29 % ( n = 6 ) of LAGB , and no intensive lifestyle weight loss intervention participants ( P = .004 ) . The use of diabetes medications was reduced more in the surgical groups than the lifestyle intervention-alone group , with 65 % of RYGB , 33 % of LAGB , and none of the intensive lifestyle weight loss intervention participants going from using insulin or oral medication at baseline to no medication at year 3 ( P .001 ) . Mean ( SE ) reductions in percentage of body weight at 3 years were the greatest after RYGB at 25.0 % ( 2.0 % ) , followed by LAGB at 15.0 % ( 2.0 % ) and lifestyle treatment at 5.7 % ( 2.4 % ) ( P Among obese participants with T2DM , bariatric surgery with 2 years of an adjunctive low-level lifestyle intervention result ed in more disease remission than did lifestyle intervention alone . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01047735", "CONTEXT Adolescent obesity is a common and serious health problem affecting more than 5 million young people in the United States alone . Bariatric surgery is being evaluated as a possible treatment option . Laparoscopic adjustable gastric b and ing ( gastric b and ing ) has the potential to provide a safe and effective treatment . OBJECTIVE To compare the outcomes of gastric b and ing with an optimal lifestyle program on adolescent obesity . DESIGN , SETTING , AND PATIENTS A prospect i ve , r and omized controlled trial of 50 adolescents between 14 and 18 years with a body mass index ( BMI ) higher than 35 , recruited from the Melbourne , Australia , community , assigned either to a supervised lifestyle intervention or to undergo gastric b and ing , and followed up for 2 years . The study was performed between May 2005 and September 2008 . MAIN OUTCOME MEASURES Weight loss . Secondary outcomes included change in metabolic syndrome , insulin resistance , quality of life , and adverse outcomes . RESULTS Twenty-four of 25 patients in the gastric b and ing group and 18 of 25 in lifestyle group completed the study . Twenty-one ( 84 % ) in the gastric b and ing and 3 ( 12 % ) in the lifestyle groups lost more than 50 % of excess weight , corrected for age . Overall , the mean changes in the gastric b and ing group were a weight loss of 34.6 kg ( 95 % CI , 30.2 - 39.0 ) , representing an excess weight loss of 78.8 % ( 95 % CI , 66.6%-91.0 % ) , 12.7 BMI units ( 95 % CI , 11.3 - 14.2 ) , and a BMI z score change from 2.39 ( 95 % CI , 2.05 - 2.73 ) to 1.32 ( 95 % CI , 0.98 - 1.66 ) . The mean losses in the lifestyle group were 3.0 kg ( 95 % CI , 2.1 - 8.1 ) , representing excess weight loss of 13.2 % ( 95 % CI , 2.6%-21.0 % ) , 1.3 BMI units ( 95 % CI , 0.4 - 2.9 ) , and a BMI z score change from 2.41 ( 95 % CI , 2.21 - 2.66 ) to 2.26 ( 95 % CI , 1.91 - 2.43 ) . At entry , 9 participants ( 36 % ) in the gastric b and ing group and 10 ( 40 % ) in the lifestyle group had the metabolic syndrome . At 24 months , none of the gastric b and ing group had the metabolic syndrome ( P = .008 ; McNemar chi(2 ) ) compared with 4 of the 18 completers ( 22 % ) in the lifestyle group ( P = .13 ) . The gastric b and ing group experienced improved quality of life with no perioperative adverse events . However , 8 operations ( 33 % ) were required in 7 patients for revisional procedures either for proximal pouch dilatation or tubing injury during follow-up . CONCLUSIONS Among obese adolescent participants , use of gastric b and ing compared with lifestyle intervention result ed in a greater percentage achieving a loss of 50 % of excess weight , corrected for age . There were associated benefits to health and quality of life . TRIAL REGISTRATION ANZCTR Identifier : 12605000160639", "BACKGROUND In short-term r and omized trials ( duration , 1 to 2 years ) , bariatric surgery has been associated with improvement in type 2 diabetes mellitus . METHODS We assessed outcomes 3 years after the r and omization of 150 obese patients with uncontrolled type 2 diabetes to receive either intensive medical therapy alone or intensive medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy . The primary end point was a glycated hemoglobin level of 6.0 % or less . RESULTS The mean ( ±SD ) age of the patients at baseline was 48±8 years , 68 % were women , the mean baseline glycated hemoglobin level was 9.3±1.5 % , and the mean baseline body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 36.0±3.5 . A total of 91 % of the patients completed 36 months of follow-up . At 3 years , the criterion for the primary end point was met by 5 % of the patients in the medical-therapy group , as compared with 38 % of those in the gastric-bypass group ( P The use of glucose-lowering medications , including insulin , was lower in the surgical groups than in the medical-therapy group . Patients in the surgical groups had greater mean percentage reductions in weight from baseline , with reductions of 24.5±9.1 % in the gastric-bypass group and 21.1±8.9 % in the sleeve-gastrectomy group , as compared with a reduction of 4.2±8.3 % in the medical-therapy group ( P for both comparisons ) . Quality -of-life measures were significantly better in the two surgical groups than in the medical-therapy group . There were no major late surgical complications . CONCLUSIONS Among obese patients with uncontrolled type 2 diabetes , 3 years of intensive medical therapy plus bariatric surgery result ed in glycemic control in significantly more patients than did medical therapy alone . Analyses of secondary end points , including body weight , use of glucose-lowering medications , and quality of life , also showed favorable results at 3 years in the surgical groups , as compared with the group receiving medical therapy alone . ( Funded by Ethicon and others ; STAMPEDE Clinical Trials.gov number , NCT00432809 . )", "OBJECTIVE To determine the 2-year outcomes of Roux-en-Y gastric bypass ( RYGB ) and sleeve gastrectomy ( SG ) vs. intensive medical therapy ( IMT ) on lean body mass , total bone mass , and bone mineral density ( BMD ) measures from the STAMPEDE trial . METHODS 54 subjects ( BMI : 36 ± 1 kg/m(2 ) , age : 48 ± 4 years ) with type 2 diabetes ( T2DM ) ( HbA1c : 9.7 ± 2 % ) were r and omized to IMT , RYGB , or SG and underwent DXA at baseline and at 1 and 2 years . RESULTS At 2 years , the reduction in BMI was similar after RYGB and SG and was greater than IMT ( P 0.001 ) . Lean mass was reduced by ∼10 % , total bone mineral content reduced by ∼8 % , and hip BMD reduced by ∼9 % in both surgical groups and was significantly greater than IMT despite increases in vitamin D intake in all groups . The change in hip BMD correlated with weight loss ( r = 0.84 , P changes in lean mass ( r = 0.74 , P 0.0001 ) . Peripheral fractures were self-reported in RYGB ( 4/18 patients ) , SG ( 2/19 patients ) , and IMT ( 4/16 patients ) . CONCLUSIONS Surgically induced weight loss is associated with modest reductions in lean mass , bone mineral content , and BMD , despite calcium and vitamin D supplementation in patients with T2DM . Awareness for bone loss is indicated for patients undergoing bariatric procedures", "CONTEXT Recommendations for surgical , compared with lifestyle and pharmacologically based , approaches for type 2 diabetes ( T2D ) management remain controversial . OBJECTIVE The objective was to compare laparoscopic adjustable gastric b and ( LAGB ) to an intensive medical diabetes and weight management ( IMWM ) program for T2D . DESIGN This was design ed as a prospect i ve , r and omized clinical trial . SETTING The setting was two Harvard Medical School-affiliated academic institutions . INTERVENTIONS AND PARTICIPANTS : A 12-month r and omized trial comparing LAGB ( n = 23 ) vs IMWM ( n = 22 ) in persons aged 21 - 65 years with body mass index of 30 - 45 kg/m(2 ) , T2D diagnosed more than 1 year earlier , and glycated hemoglobin ( HbA(1c ) ) ≥ 6.5 % on antihyperglycemic medication(s ) . MAIN OUTCOME MEASURE The proportion meeting the prespecified primary glycemic endpoint , defined as HbA(1c ) fasting glucose 40 initiating intervention ( 22 males/18 females ; age , 51 ± 10 y ; body mass index , 36.5 ± 3.7 kg/m(2 ) ; diabetes duration , 9 ± 5 y ; HbA(1c ) , 8.2 ± 1.2 % ; 40 % on insulin ) , the proportion meeting the primary glycemic endpoint was achieved in 33 % of the LAGB patients and 23 % of the IMWM patients ( P = .457 ) . HbA(1c ) reduction was similar between groups at both 3 and 12 months ( -1.2 ± 0.3 vs -1.0 ± 0.3 % ; P = .496 ) . Weight loss was similar at 3 months but greater 12 months after LAGB ( -13.5 ± 1.7 vs -8.5 ± 1.6 kg ; P = .027 ) . Systolic blood pressure reduction was greater after IMWM than LAGB , whereas changes in diastolic blood pressure , lipids , fitness , and cardiovascular risk scores were similar between groups . Patient-reported health status , assessed using the Short Form-36 , Impact of Weight on Quality of Life , and Problem Areas in Diabetes , all improved similarly between groups . CONCLUSIONS LAGB and a multidisciplinary IMWM program have similar 1-year benefits on diabetes control , cardiometabolic risk , and patient satisfaction , which should be considered in the context of other factors , such as personal preference , when selecting treatment options with obese T2D patients . Longer duration studies are important to underst and emergent differences" ]	411898d4-06ff-11f0-808a-c43d1ab1c353
STUDY DESIGN A systematic literature review of outcome question naires design ed for assessing functional status or disability in patients with low back pain . OBJECTIVES To provide a comprehensive overview of all functioning/disability question naires used in recent years and to explore how the main concept(s ) was described or defined in the original paper , the content or the domains of disability , and the measurement properties of the question naires . SUMMARY OF BACKGROUND DATA A number of clinical tools design ed for evaluating the functional status of patients with low back pain have been developed . Only a few have been review ed earlier , and there has been little focus on the content reflected in the question naires . METHODS Papers including question naires for assessing disability , function , activity limitations , or participation restrictions in adult patients with low back pain were search ed in the MEDLINE and CINAHL data bases for the period from January 1996 to January 2002 . Two independent and blinded research ers read and selected abstract s and question naires . The content of the included question naires was classified according to World Health Organization 's International Classification of Functioning , Disability and Health . The measurement properties were analyzed according to recommended guidelines . RESULTS A total of 36 back-specific question naires were identified . When distinguishing among a bodily , personal , and social perspective of functioning , 4 main types of content were identified . Most of the outcome question naires had a mixed content reflecting various constructs such as pain and symptoms , sleep disturbances , psychological dysfunctions , physical impairments , and social functions . Nine question naires assessed solely activities of daily living . For one-third of the question naires , the measurement properties were reported in only the original study . CONCLUSIONS Although most question naires had their main focus on activity limitations , a considerable variation with respect to the main concept and content was found . Only a few of the question naires can be considered acceptably vali date	[ "Study Design . A prospect i ve repeated- measures design was applied . Objectives . To examine the measurement properties of the Back Pain Functional Scale ( BPFS ) and the Rol and –Morris Question naire ( RMQ ) and to formulate hypotheses and sample size estimates for a subsequent comparison study . Summary of Background Data . Although there are numerous functional status measures for patients with low back pain , most have been conceived of and vali date d with a group rather than an individual patient as the unit of interest . Also , little has been done to formally compare — this includes the generation of a priori hypotheses , followed by statistical hypotheses testing — the many competing measures . Methods . Subjects were 77 patients with low back pain who were referred by physicians to 10 outpatient physical therapy clinics located in Canada and the United States . The question naires were administered at patients ’ initial visits , within 48 hours of the initial visit , and at 1- , 2- , and 3-week follow-up visits . Reliability , cross-sectional validity , and longitudinal validity ( sensitivity to change ) coefficients were calculated . Results . Test – retest reliability estimates of 0.81 and 0.88 were obtained for the RMQ and BPFS , respectively . The measures demonstrated similar levels of cross-sectional validity . Correlations of 0.56 and 0.65 were noted between a prognostic rating of change and the RMQ and BPFS , respectively . The RMQ demonstrated a ceiling effect . Approximately 180 patients are needed for a subsequent head-to-head comparison study of the measures . Conclusions . The BPFS appears to have sound measurement properties , and a formal head-to-head comparison study with the RMQ is warranted", "Study Design . Prospect i ve study of two sample s of patients with acute and chronic low back pain , respectively . Objectives . To compare the responsiveness of four functional status question naires , Rol and Morris Disability Question naire ( RMDQ ) , Oswestry Disability Index ( ODI ) , Disability Rating Index ( DRI ) , and Physical Functioning scale of the SF-36 ( PFSF-36 ) , and two pain scales , a Numerical Pain Rating Scale ( NRS ) and Visual Analogue Scale ( VAS ) . Summary of Background Data . Concurrent comparisons of different outcome measurements in back patients have been requested . Methods . Norwegian versions of the scales and question naires were completed by 54 patients with acute ( 3 months ) . Clinical change was estimated on a global change index . An alternative external criterion was the expected clinical course in the two cohorts . Mean changes , st and ardized response mean ( SRM ) , and area under the receiver operating characteristic ( ROC ) curves with cutoff point for highest sensitivity and specificity were calculated . Results . At the follow-up , 63 % of the acute and 41 % of the chronic sample reported improvement on the global change index . Large SRMs ( 1.3–2.0 ) and areas under the ROC curves ( 0.84–0.93 ) were found for the measurements in the acute sample . In the chronic sample , the SRMs ( 0.4–1.1 ) and areas under the ROC curves ( 0.65–0.83 ) were lower , in particular for the PFSF-36 and the VAS . There was no statistically significant difference between the responsiveness in the measurements , except for higher responsiveness in the NRS compared with the VAS when using expected clinical course as the external criterion for change . Conclusion . The results suggest that all the outcome measures were appropriate for measuring changes in functional status and pain in patients with acute low back pain , whereas among chronic patients the RMDQ , ODI , DRI , and NRS were most appropriate", "BACKGROUND Chronic low-back pain is a significant public health problem for which few therapies are supported by predictable outcomes . In this report , practice activities and 1-month outcomes data are presented for 93 chiropractic patients and 45 medical patients with chronic , recurrent low-back pain . DESIGN A prospect i ve , observational , community-based feasibility study involving chiropractors and family medicine physicians . SETTING Forty private chiropractic clinics , the outpatient clinic of the Department of Family Medicine at Oregon Health Sciences University , and 5 other Portl and area family medicine clinics . OUTCOMES MEASURES The main outcome measures were pain severity , functional disability , sensory and affective pain quality at 1 month , and patient satisfaction assessed at 7 to 10 days and at 1 month . RESULTS Although differences were noted in age , sex , education , and employment , the patients were closely matched at baseline with respect to frequency , severity , and type of low-back pain and the psychosocial dimensions of general health . The treatment of choice for chiropractors was spinal manipulation and physical therapy modalities ; for medical physicians antiinflammatory agents were most frequently used . Chiropractic patients averaged 4 visits , and medical patients averaged 1 visit . On average , chiropractic patients showed improvement across all outcomes : 31 % change in pain severity , 29 % in functional disability , 36 % in sensory pain quality , and 57 % in affective pain quality . Medical patients showed minimal improvement in pain severity ( 6 % ) and functional disability ( 1 % ) and showed deterioration in the sensory ( 29 % ) and affective ( 26 % ) dimensions of pain quality . Satisfaction scores were higher for chiropractic patients . Outcomes for medical patients were heavily dependent on psychosocial status at baseline . CONCLUSION Patients with chronic low-back pain treated by chiropractors show greater improvement and satisfaction at 1 month than patients treated by family physicians . Non clinical factors may play an important role in patient progress . Findings from the Health Re sources and Services Administration-funded project will include a report on the influence of practice activities , including more frequent visits by chiropractic patients , on the clinical course of low-back pain and patient outcomes . ( J Manipulative Physiol Ther 2000;23:239 - 45 )", "STUDY DESIGN A prospect i ve , cross-sectional study of the correlation between postoperative computed tomography findings and patients ' clinical outcomes approximately 4 years after laminectomy for lumbar spinal stenosis . OBJECTIVES To evaluate clinical and radiologic characteristics and their relation to each other . SUMMARY OF BACKGROUND DATA The goal of surgical management for lumbar spinal stenosis is to decompress the stenotic area determined in radiologic examinations to relieve pressure on the neurovascular structures . However , the success of this decompression very rarely has been confirmed by postoperative radiologic imaging or compared with clinical outcome . METHODS Postoperative computed tomography was performed on 191 patients . The findings were classified as \" no stenosis , \" \" central stenosis , \" \" lateral stenosis , \" or \" central -lateral stenosis . \" Postoperative instability of the lumbar spine was investigated by functional radiography . Clinical status was assessed by clinical examination . Subjective disability was assessing using the Oswestry question naire , and severity of pain using the visual analog scale . Walking capacity was evaluated by the tread-mill test . RESULTS Radiologic studies revealed postoperative stenosis in 123 patients ( 64 % ) . Small differences between the computed tomography groups were shown for the Oswestry score , but not for walking distance . Clinical signs , severity of pain , and radiologic instability were very similar for all computed tomography groups . CONCLUSIONS Postoperative radiologic stenosis was very common in patients operated on for lumbar spinal stenosis , but this did not correlate with clinical outcome . The clinician must be cautious when reconciling clinical symptoms and signs with postoperative computed tomography findings in patients operated on for lumbar spinal stenosis", "STUDY DESIGN A double-blind , r and omized controlled trial of a novel educational booklet compared with a traditional booklet for patients seeking treatment in primary care for acute or recurrent low back pain . OBJECTIVE To test the impact of a novel educational booklet on patients ' beliefs about back pain and functional outcome . SUMMARY OF BACKGROUND DATA The information and advice that health professionals give to patients may be important in health care intervention , but there is little scientific evidence of their effectiveness . A novel patient educational booklet , The Back Book , has been developed to provide evidence -based information and advice consistent with current clinical guidelines . METHODS One hundred sixty-two patients were given either the experimental booklet or a traditional booklet . The main outcomes studied were fear-avoidance beliefs about physical activity , beliefs about the inevitable consequences of back trouble , the Rol and Disability Question naire , and visual analogue pain scales . Postal follow-up response at 1 year after initial treatment was 78 % . RESULTS Patients receiving the experimental booklet showed a statistically significant greater early improvement in beliefs which was maintained at 1 year . A greater proportion of patients with an initially high fear-avoidance beliefs score who received the experimental booklet had clinical ly important improvement in fear-avoidance beliefs about physical activity at 2 weeks , followed by a clinical ly important improvement in the Rol and Disability Question naire score at 3 months . There was no effect on pain . CONCLUSION This trial shows that carefully selected and presented information and advice about back pain can have a positive effect on patients ' beliefs and clinical outcomes , and suggests that a study of clinical ly important effects in individual patients may provide further insights into the management of low back pain", "Study Design . A prospect i ve cohort study of patients with subacute occupational back pain . Objectives . To study the relation between a marketed opto‐electric device measuring trunk kinematics , a widely used specific functional capacity question naire , and work status in back pain patients , and to assess the responsiveness to change in work status of the opto‐electric device and the question naire . Summary of Background Data . Several instruments have been developed to evaluate the functional capacities of patients with back pain , but the relation between these instruments and work status has rarely been studied . Methods . The relation between the opto‐electric device , the question naire , and work status in patients with back pain was evaluated . The study population was a prospect i ve cohort of patients with subacute back pain who were absent from regular work for more than 4 weeks . All data were compiled blindly on the same day , at study entry ( 4 weeks after work accident ) , and at 12 , 24 , and 52 weeks after the work accident . The validity of the question naire and opto‐electric device scores was assessed with partial correlation analyses , st and ardized response mean , logistic regression analyses , and receiver operating characteristics curves . Results . The correlation between the question naire and opto‐electric device scores was low . The question naire scores were significantly related to work status , but the opto‐electric device scores were not . The question naire was responsive to change in work status , whereas the opto‐electric device was not . Conclusions . The opto‐electric device scores were not related to either functional capacity scores ( question naire ) or work status in patients with low back pain , and the opto‐electric device was not responsive to change in work status . Conversely , the question naire was related to work status and was responsive to change in work status", "OBJECTIVE Previous studies have shown that cortical-evoked potentials on magnetic stimulation of muscles are influenced by muscle contraction , vibration , and muscle spasm . This study was carried out to determine whether these potentials correlate with palpatory muscle spasm , patient symptoms , and disability in patients with low back pain . METHODS A prospect i ve observational study was performed on 13 subjects with a history of low back pain visiting an orthopedic hospital-based clinic . Patients were screened for serious pathologic conditions by an orthopedic surgeon . The patients were then evaluated for the presence of muscle spasm by one of the investigators who was blinded to the results of the evoked potential studies . Patients were asked to complete a low back pain visual analogue scale ( VAS ) and a Rol and -Morris Activity Scale ( RMAS ) . Cortical-evoked potentials were recorded with a magnetic stimulator placed over the lumbar paraspinal muscles with the patient in the prone position . The palpatory examination , VAS , RMAS , and the cortical potentials were repeated after 2 weeks of therapy commonly used to reduce muscle spasm . RESULTS The patients demonstrated a significant decrease in low back pain VAS and RMAS scores after treatment compared with before treatment . There was a reduction in the amount of palpatory muscle spasm in 11 of 13 cases . The cortical potentials before treatment were attenuated compared with previously reported controls and showed a significant increase before and after treatment in the amplitude of these potentials with multivariate analysis of variance . There was significant correlation between the changes in cortical potentials after treatment and the changes noted in paraspinal muscle spasm and VAS and RMAS scores . CONCLUSIONS This study confirms the previous report that the amplitude of cerebral-evoked potentials on magnetic stimulation of paraspinal muscles is depressed in the presence of palpable muscle spasm . The close correlation among these potentials , paraspinal muscle spasm , and clinical symptoms suggests that the measurement of muscle activity may be more important in the assessment of low back pain than is commonly accepted", "Study Design . Analysis of longitudinal data collected prospect ively from patients seen in 27 National Spine Network member centers across the United States . Objective . To evaluate the responsiveness of the Oswestry Disability Index , MODEMS scales , and all scales and summary scales of the MOS Short-Form 36 ( SF-36 ) for patients with low back pain/leg symptoms . Summary of Background Data . The responsiveness of general and condition-specific health status instruments is a key concept for clinicians and scientists . Various authors have explored responsiveness in common surveys used to assess spine patients . Although it is generally believed that condition-specific measures are more responsive to change in the condition under study , in the case of low back pain , most authors agree that further exploration is necessary . Methods . Patients with diagnoses of herniated disc , spinal stenosis , and spondylosis from the National Spine Network data base who completed baseline and 3-month follow-up surveys were analyzed . Patient-provider consensus regarding improvement , worsening , or no change in the condition was selected as the external criterion . Responsiveness was evaluated using ROC curve analysis and effect size calculations . Results . Nine hundred and seventy patients had complete data at baseline and 3 months . At follow-up , 68 % of the patients had consensus improvement . Based on ROC analysis , scales assessing pain were significantly more responsive than scales assessing function . There were no significant differences between the condition-specific scales and their equivalent general-health counterpart . The scales with the highest probabilities of correctly identifying patient ’s improvement were : the condition-specific pain scale from MODEMS ( PAIN , ROC = 0.758 ) ; the combined pain and function scale from MODEMS ( MPDL , ROC = 0.755 ) ; the general pain scale from the SF-36 ( BP , ROC = 0.753 ) ; the combined pain and function scale from the SF-36 ( PCS , ROC = 0.745 ) ; the condition-specific function measure from the Oswestry ( ODI , ROC = 0.723 ) ; and the physical function measure from the SF-36 ( PF , ROC = 0.721 ) . A similar rank order was typically maintained with effect size calculations . Results were nearly identical in patients with multiple non-spine-related comorbidities and in patients with high degrees of perceived disability . The BP scale was most responsive to worsening of symptoms . Conclusion . For studies of patients with low back problems , the general SF-36 may be a sufficient measure of health status and patient function , without the need for additional condition-specific instruments . Pain scales appear to be the most responsive measures in patients with low back pain", "Abstract . When measuring treatment effect in chronic low back pain with multi-item outcome instruments , it is necessary , both for clinical decision-making and research purpose s , to underst and the clinical importance of the outcome scores . The aims of the present study were three-fold . Firstly , it aim ed to estimate the minimal clinical ly important difference of three multi-item outcome instruments ( the Oswestry Disability Index , the General Function Score and the Zung Depression Scale ) and of the visual analogue scale ( VAS ) of back pain . Secondly , it aim ed to estimate the error of measurement of these instruments ; and its third aim was to describe the clinical meaning of score change . The study population consisted of 289 patients treated surgically or non-surgically in a r and omised controlled trial . The minimal clinical ly important difference was estimated with patient global assessment as the external criterion . It was compared with the st and ard error of measurement of the instruments . The individual items of the instruments were compared for score changes related to improvement and deterioration . The st and ard error of measurement of the Oswestry Disability Index , the General Function Score and the Zung Depression Scale was 4 , 6 and 3 units , respectively . The 95 % tolerance interval was 10 , 16 and 8 units , respectively . The minimal clinical ly important difference was 10 , 12 and 8–9 units , respectively , thus not significantly exceeding the tolerance interval . The minimal clinical ly important difference of VAS back pain was 18–19 units , well exceeding the 95 % tolerance interval , which was 15 units . Improvement after treatment for chronic low back pain tends to occur to a greater extent in sleep disturbance , ability to do usual things and psychological irritability , but to a lesser extent in the ability to sit , st and and lift . We conclude that the VAS of back pain is responsive enough to detect the minimal clinical ly important difference , whereas the smallest acceptable score changes of the Oswestry Disability Index , the General Function Score and the Zung Depression Scale may require an increase to exceed the 95 % tolerance interval when used for clinical decision making and for power calculation . Despite improvement after treatment , the ability to sit , st and and lift , remain notable problems", "STUDY DESIGN A prospect i ve cohort study assessing the responsiveness of two disease-specific question naires and a generic health question naire for patients with low back pain and sciatica . OBJECTIVES To compare the responsiveness of the eight scales and two summery scales of the SF-36 question naire with that of the Oswestry Disability Index and Low Back Outcome Score question naires . SUMMARY OF BACKGROUND DATA Evaluation of treatment outcome is being determined more frequently from a patient 's perspective , particularly the impact treatment has on current health status . METHODS Patients were recruited from two orthopedic back pain clinics in a tertiary hospital . Patients completed the pretreatment question naire 1 month before treatment and follow-up question naires a minimum of 2 - 6 months after treatment . Patients undergoing surgery were also observed for a minimum of 2 years . RESULTS Overall , the Oswestry Disability Index was most responsive ; however , individual scales from the SF-36 question naire showed equal or greater sensitivity to change than the Oswestry Disability Index in each of the patient subgroups . The SF-36 Role Physical scale was prone to floor effects ( a high percentage of respondents score zero ) , and the change scores from the SF-36 Role Emotional scale varied by 100 points in either direction in each of the patient subgroups . CONCLUSION Responsiveness varied according to which method was used in its calculation . The responsiveness of the SF-36 question naire shows that it can be a useful adjunct in the assessment of patients with low back pain when combined with disease-specific question naires", "STUDY DESIGN We conducted a prospect i ve study with a 2-year follow-up . OBJECTIVE To compare pain , functional limitations , and work status indices as measures of outcome among back pain patients . SUMMARY OF BACKGROUND DATA Work status , pain , and functional limitations indices are often considered as interchangeable outcome measures in back pain research . This perspective has been criticized by several authors , who argue that each of these outcome measures reflects a different construct that may vary independently of the others . METHODS The study was conducted on 720 patients , who sought care for back pain in primary care setting s of a large health maintenance organization in 1989 - 90 , and were interviewed one month and two years later . X2 analyses and receiver operating characteristic curves were used to compare the accuracy of a pain rating and a modified 16-item Rol and -Morris score in classifying patients on work status and on the change in work status over time . RESULTS Moderate agreement between the pain and functional limitations measures and work status was observed . Pain and functional limitations change scores agreed moderately with improvement in work status , but were poorly associated with decline in work status . CONCLUSIONS Although the pain , functional limitations , and work status indices examined in this study are related , they are not equivalent and should not be regarded as interchangeable . These results argue for a clearer distinction of outcome measures in back pain research", "BACKGROUND AND PURPOSE This study compared the ability of the Rol and -Morris ( RM ) , Oswestry ( OSW ) , and Jan van Breemen Institute ( JVB ) pain and function question naires to detect change over time . SUBJECTS The sample consisted of 88 patients with mechanical low back pain who were referred by physicians to the outpatient physical therapy department of a teaching hospital . METHODS Question naires were completed by the subjects at their initial visit and 4 to 6 weeks later . Clinical ly important change was estimated by having the subject and the clinician independently complete two rating scales . Sensitivity to change was assessed using receiver operating characteristic ( ROC ) curve analysis . RESULTS The ROC curve areas for the RM ( 0.79 ) , OSW ( 0.78 ) , and JVB pain ( 0.79 ) question naires were significantly greater than for the JVB function question naire ( 0.66 ) . Blank and multiple responses per item were present on approximately 20 % of the OSW question naires and 14 % of the JVB question naires . Words rather than checks were evident on 3 % of the RM question naires . CONCLUSION AND DISCUSSION Based on the latter finding , we believe the RM question naire may be the preferred instrument for assessing change over time in patients with low back pain", "Bayramoğlu M , Akman MN , Kılınç Ş , Çetin N , Yavuz N , Özker R : Isokinetic measurement of trunk muscle strength in women with chronic low-back pain . Am J Phys Med Rehabil 2001;80:650–655 . Objectives : To investigate the relationships among chronic low-back pain and obesity , total spinal range of motion , and trunk muscle strength . The short-term impact of trunk muscle strengthening exercises on this condition was also examined . Design : A controlled , prospect i ve study of trunk muscle strengths of patients with chronic low-back pain and the short-term impact of exercise on strength . The study group consisted of 25 female patients who had been experiencing low-back pain for at least 3 mo , and the control group included 20 age-matched women without known low-back trouble . The Davenport Index was used to calculate the body mass indexes of all subjects . The Oswestry Disability Question naire was used to assess pain in the study group . Full flexion and extension ranges of motion were measured , then isokinetic measurements of trunk muscles were performed at 60- , 120- , and 180-degrees/sec velocities . Isometric measurements were also recorded for both flexors and extensors at a 60-degree angle . Results : Increased body mass index and decreased trunk muscle strength were found to be directly associated with chronic low-back pain ( P st and ard trunk strengthening exercise program in the patient group , trunk muscle strength was found to be increased ( P < 0.05 ) . Conclusions : Obesity and decrease in trunk muscle strength are important factors in chronic low-back pain , and a trunk muscle strengthening program will be helpful in reducing the pain", "Objective : To investigate the validity of the spinal range of motion models outlined in the second and fourth editions of the American Medical Association Guides to the evaluation of permanent impairment ( AMA Guides ) , for assessing the percentage impairment in chronic low back pain patients . Design : Cross-sectional validation study . Setting : Outpatient department in the Rehabilitation Medicine Unit . Subjects : A volunteer sample of 34 subjects participated in the study , 21 females and 13 males , with a mean age of 47.7 years ( 1 SD = 12.1 ) and 40.1 years ( 1 SD = 11.1 ) , respectively . Subjects had chronic low back with or without leg pain of at least six months ’ duration . Subjects were recruited by medical practitioners and physiotherapists through the Rehabilitation Unit at the Essendon Campus of Royal Melbourne Hospital . Main outcome measures : Lower back range of motion measured with a long arm goniometer and a dual inclinometer , Waddell Physical Impairment Scale , Waddell Disability Index , Oswestry Disability Index . Results : Both range of motion measurement methods demonstrated poor validity and do not bear any consistent relationship to the level of physical or functional impairment in subjects with chronic low back pain . Conclusions : There was no evidence for a relationship between low back range of motion and impairment , and thus it would appear illogical to evaluate impairment in chronic low back pain patients using a spinal range of motion model when aim ing to measure or compensate disability", "Study Design This study analyzed health-related quality -of-life measures and other clinical and question naire data obtained from the Maine Lumbar Spine Study , a prospect i ve cohort study of persons with low back problems . Objective For persons with sciatica , back pain-specific and general measures of health-related quality -of-life were compared with regard to internal consistency , construct validity , reproducibility , and responsiveness in detecting small changes over a 3-month period . Summary of Background Data Data were collected from 427 participants with sciatica . Baseline in-person interviews were conducted with surgical and medical patients before treatment and by mail at 3 months . Methods Health-related quality -of-life measures included symptoms ( frequency and bothersomeness of pain and sciatica ) functional status and well-being ( modified back pain-specific Rol and scale and Medical Outcomes Study 36-item Short Form Health Survey ( SF-36 ) , and disability ( bed rest , work loss , and restricted activity days ) . Results Internal consistency of measures was high . Reproducibility was moderate , as expected after a 3-month interval . The SF-36 bodily pain item and the modified Rol and measure demonstrated the greatest amount of change and were the most highly associated with self-rated improvement . The specific and generic measures changed in the expected direction , except for general health perceptions , which declined slightly . A high correlation between clinical findings or symptoms and the modified Rol and measure , SF-36 , and disability days indicated a high degree of construct validity . Conclusions These measures performed well in measuring the health-related quality -of-life of patients with sciatica . The modified Rol and and the physical dimension of the SF-36 were the measures most responsive to change over time , suggesting their use in prospect i ve evaluation . Disability day measures , although valuable for assessing the societal impact of dysfunction , were less responsive to changes over this short-term follow-up of 3 months", "Abstract Failed back surgery syndrome ( FBSS ) is an important complication of lumbar disc surgery . Epidural fibrosis is one of the major causes of FBSS . However , most patients with epidural fibrosis do not develop symptomatic complaints from scarring . The purpose of this prospect i ve study was to evaluate the relationships among the severity of epidural fibrosis , psychological factors , back pain and disability after lumbar disc surgery . Twenty-nine surgically managed patients ( 13 women , 16 men ) were included in this study . In all patients , the presence and severity of epidural fibrosis was determined with contrast-enhanced magnetic resonance imaging ( MRI ) . A pain visual analog scale ( VAS ) and Oswestry Disability Question naire ( ODQ ) were completed before and after surgery . Subjects were grouped by their type of herniation ( protrusion , free fragment ) , MRI findings and results of the mini form of the Minnesota Multiphasic Personality Inventory ( MMPI ) , and the groups were compared for their VAS and ODQ scores . Our results disclosed that neither the postoperative VAS scores nor the postoperative ODQ scores differed significantly among the epidural fibrosis severity groups . Moreover , postoperative VAS scores were positively correlated with the scores of the mini MMPI . These findings indicate that epidural fibrosis may be considered as a radiological entity independent of patients ’ complaints . Furthermore , the mini MMPI should be included in the assessment and planning of the reoperations in FBSS patients , because of the importance of psychological factors in postoperative pain and disability", "BACKGROUND AND PURPOSE Spinal and muscle flexibility have been studied intensively and used clinical ly as outcome measurements in the rehabilitation of subjects with low back pain . The results of previous studies are contradictory and there is a lack of longitudinal data on the effects of long term therapeutic exercise on flexibility . METHOD A controlled experimental study was conducted to determine the effects of progressive therapeutic exercise on spinal and muscle flexibility . Eighty-six chronic low back pain subjects fulfilled the inclusion criteria and were divided into three study groups : ( 1 ) intensive training group , ( 2 ) home exercise group and ( 3 ) control group . The intervention period lasted three months and measurements were performed at both the beginning of the study and immediately after intervention . Follow-up measurements were carried out six and 12 months after baseline . Spinal flexibility was measured with lumbar flexion , extension , spinal lateral flexion and rotation , and muscle flexibility was measured with measurements of erector spinae , hamstring and iliopsoas muscles . Also self-reported outcomes of the Oswestry Index and Borg Scale -- Back Pain Intensity were used . Associations between change ( pre- to post-treatment ) were determined for the dependent variables . RESULTS The results showed no correlation between flexibility , the Oswestry Index or back pain intensity . After the first three-month period lumbar flexion , extension and spinal rotation decreased among all subjects . Spinal rotation and erector spinae muscle flexibility improved significantly with intensive training . At the nine-month follow-up , erector spine flexibility was still greater than at baseline . Hamstring flexibility increased among the intensive training and home exercise groups from pre- to post-intervention . However , the degree of hamstring flexibility gained during training was subsequently lost following the period without programmed exercise in both training groups . Self-reported outcome variables showed positive changes among the three study groups after the completion of intervention period , but these changes were only able to be maintained during subsequent follow-ups for the intensive training and home exercise groups . CONCLUSIONS The findings suggest that flexibility does not play an important role in coping with chronic low back pain for subjects whose functional limitations are not severe . Also , it appears that the achieved gains in spinal and muscle flexibility may not be able to be maintained without continued exercise", "OBJECTIVE To undertake a comparative examination of the reliability and validity of two frequently used self-report measures of functional disability , the Pain Disability Index ( PDI ) and the Oswestry Low Back Pain Disability Question naire ( OLBPDQ ) . DESIGN A descriptive ex-post facto design was used in the study . SETTING Pain clinics and neurosurgical units at three metropolitan hospitals . SUBJECTS One hundred patients with chronic low back pain of noncancer origin were administered the two question naires as part of a larger question naire battery . RESULTS Acceptable internal consistency values of 0.76 for the PDI and 0.71 for the OLBPDQ were obtained . A correlation of r = 0.63 was found between the PDI and the OLBPDQ , supporting the concurrent validity of the two scales . Both the scales were found to be correlated to the Beck Depression Inventory scores ( PDI , r = 0.42 ; OLBPDQ , r = 0.39 ) , with higher disability associated with greater depression . Only the total PDI score was found to be sensitive to functional status differences within the patient sample . CONCLUSIONS These findings support other recent work in favor of the PDI . The PDI had a slightly higher internal consistency and was more sensitive than the OLBPDQ", "Study Design . The Shuttle Walking Test ( SWT ) , the Swiss Spinal Stenosis ( SSS ) Question naire , the Oxford Claudication Score ( OCS ) , and the Oswestry Disability Index ( ODI ) were administered to patients with lumbar spinal stenosis and neurogenic claudication . Objective . To determine reliability of the SWT , the SSS ( Q1–12 ) , the OCS , and the ODI in lumbar spinal stenosis assessment . Summary of Background Data . Reliability data for exercise tests in lumbar spinal stenosis are lacking . Methods . To determine reliability , 32 clinic patients with lumbar spinal stenosis were assessed twice , with 1 week between assessment s. Retrospective data from 17 patients assessed before surgery and 18 months after surgery for lumbar spinal stenosis were used to investigate the use of reliability in a clinical setting . Results . Test – retest reliability in terms of the intraclass correlation coefficient ( ICC ) was 0.92 for the SWT , 0.92 for the SSS , 0.83 for the OCS and 0.89 for the ODI . The mean percentage scores were 51 for the SSS , 45 for the OCS , and 40 for the ODI . To achieve 95 % certainty of change between assessment s for a single patient , the SSS would need to change by 15 , the OCS by 20 , and the ODI by 16 . The mean SWT was 150 m , with a change of 76 m required for 95 % confidence . Cronbach ’s alpha was 0.91 for the SSS , 0.90 for the OCS , and 0.89 for the ODI . The change in ODI correlated most strongly with patient satisfaction after surgery ( & rgr ; = 0.80;P SSS , OCS , and ODI question naires are broadly similar , the most precise being the condition-specific SSS . The SWT gives a snapshot of physical function , which is acceptable for group analysis . Use of the SWT for individual assessment after surgery is feasible", "A longitudinal , prospect i ve study was conducted on 3,020 aircraft employees to identify risk factors for reporting acute back pain at work . The premorbid data included individual physical , psychosocial , and workplace factors . During slightly more than 4 years of follow-up , 279 subjects reported back problems . Other than a history of current or recent back problems , the factors found to be most predictive of subsequent reports in a multivariate model were work perceptions and certain psychosocial responses identified on the Minnesota Multiphasic Personality Inventory ( MMPI ) . Subjects who stated that they “ hardly ever ” enjoyed their job tasks were 2.5 times more likely to report a back injury ( P = 0.0001 ) than subjects who “ almost always ” enjoyed their job tasks . The quintile of subjects scoring highest on Scale-3 ( Hy ) of the MMPI were 2.0 times more likely to report a back injury ( P = 0.0001 ) than subjects with the lowest scores . The multivariate model , including job task enjoyment , MMPI Scale-3 , and history of back treatment , revealed that subjects in the highest risk group had 3.3 times the number of reports in the lowest risk group . These findings emphasize the importance of adopting a broader approach to the multifaceted problem of back complaints in industry and help explain why past prevention efforts focusing on purely physical factors have been unsuccessful", "OBJECTIVE Develop and test a short-form comprehensive outcome measure for back pain . DESIGN Prospect i ve longitudinal study of 3 consecutive cohorts of back pain patients . SETTING Anglo-European College of Chiropractic outpatient clinic and several field chiropractic practice s. METHOD Domains judged important in the back pain model and responsive to clinical change were identified from the literature . Items were scored on an 11-point numerical rating scale . The instrument was psychometrically tested by use of those tests relevant to an evaluative measure . RESULTS Seven dimensions of the back pain model were included in the question naire . Having established face validity , the instrument was shown to demonstrate high internal consistency ( Cronbach 's alpha = 0.9 ) and good test-retest reliability ( ICC = 0.95 ) . All items were retained on the basis that they contributed to the overall score ( item-corrected total score correlations ) and to the instrument 's responsiveness to clinical change ( item change-corrected total change score correlations ) . The instrument demonstrated acceptable construct and longitudinal construct validity with established external measures . The effect size of the instrument was high ( 1.29 ) and comparable with established measures . CONCLUSION A reliable , valid , and responsive instrument has been developed for use in back pain patients . It is practical for use in investigations of both the efficacy and effectiveness of back pain treatments", "Study Design A prospect i ve cohort study of patients in Maine with sciatica and lumbar spinal stenosis treated surgically and nonsurgically . Summary of Background Data In 1987 , the Quebec Task Force on Spinal Disorders proposed a diagnostic classification to help make clinical decisions , evaluate quality of care , assess prognosis , and conduct research . Objectives To assess the Quebec Task Force classification 's ability to stratify patients according to severity and treatment at baseline , and to assess changes over time in health‐related quality of life , including symptoms , functional status , and disability . Methods Five hundred sixteen patients participating in the Maine Lumbar Spine Study who completed baseline and 1‐year follow‐up evaluations were classified successfully according to the Quebec Task Force classification . Patient characteristics and treatments were compared across Quebec Task Force classification categories . Changes in health‐related quality of life over 1 year were assessed according to Quebec Task Force classification category and type of treatment . Results Among patients with sciatica ( n = 370 ) , higher Quebec Task Force classification categories ( from 2 , pain radiating to the proximal extremity , to 6 , sciatica with evidence of nerve root compression ) were associated with increased severity of symptoms at baseline . There was no association between Quebec Task Force classification and baseline functional status . Quebec Task Force classification was associated strongly with the likelihood of receiving surgical treatment ( P ≤ 0.005 ) . Among patients with sciatica treated nonsurgically , improvement at 1 year in back‐specific and generic physical function increased with higher Quebec Task Force classification category ( P ≤ 0.05 ) . Only a nonsignificant trend was observed for surgically treated patients . Patients with lumbar spinal stenosis ( Quebec Task Force classification 7 , n = 131 ) had baseline features and outcomes distinct from patients with sciatica . Conclusions For patients with sciatica , the Quebec Task Force classification was highly associated with the severity of symptoms and the probability of subsequent surgical treatment . Nonsurgically treated patients in Quebec Task Force classification categories reflecting nerve root compression had greater improvement than those with pain symptoms alone . Among surgical patients , the Quebec Task Force classification was not associated with outcome . These results provide validation for the classification and its wider adoption . Nonetheless , improved diagnostic classifications are needed to predict outcomes better in patients with sciatica who undergo surgery", " A total of 113 patients , excluding those with tumor , spondylitis , and idiopathic scoliosis , underwent anterior lumbar interbody fusion ( ALIF ) with autologous iliac crest graft between 1984 and 1991 at our department . The proportion of these who were failed back patients was higher than that reported in the literature . Evaluation of functional outcome was feasible in 80 patients , utilizing Oswestry and Marburg scores , which were closely intercorrelated . The overall results yielded an improvement in the Oswestry score of 35.7 percentage points . A subset of 52 patients who were evaluated twice , showed the same results at an average of 6.6 years as they did at 2.3 years following surgery . Functional results showed a weak correlation with postoperative height loss of the intervertebral space . Influencing factors for the functional result were : postoperative compensation cl aim , age , and obesity . Of the professional people involved , 19.4 % did not return to any occupation . Patients satisfied with the result had significantly greater functional improvement . Younger patients with additional dorsal distraction prior to ALIF for reduction of severe spondylolisthesis fared better than patients with ALIF alone . The rate of complications was low and did not contribute to the postoperative functional result . On the basis of these results further prospect i ve studies have been design ed and are currently underway", "Study Design . A comparative evaluation of outcome instruments and global assessment was performed . Objective . To test patient global assessment as a substitute for the use of more comprehensive outcome instruments in treatment trials of chronic low back pain . Summary of Background Data . Treatment outcome can be measured with pain scales and functional instruments . In the absence of a gold st and ard , the patient him- or herself is the basic reference for outcome , for which the instruments give a more or less exact measurement . Global assessment , which is a retrospective recording , may overestimate improvement as a result of recall or motivational bias . Methods . In this study , 294 patients treated for chronic low back pain were evaluated with a visual analog scale for back pain , the Oswestry Disability Index , the Million Score and general function score for disease-specific disability , and the Zung Depression Scale for depressive symptoms . The correlation between the pretreatment and posttreatment scores for the outcome instruments ( & Dgr ; scores ) and the global assessment scores was calculated ; effect sizes were compared ; sensitivity and specificity with receiver operating characteristics ( ROC ) curves were estimated ; and associations of global assessment with pretreatment and posttreatment scores were determined . Results . All the & Dgr ; scores showed significant correlations with patient global assessment and with each other . The effect size of global assessment tended to be greater than that of the outcome instruments . The specificity and sensitivity of the disability instruments and pain scale were approximately 75 % , whereas they were lower for depression . The associations between global assessment and outcome instrument scores did not produce evidence that global assessment was biased . Conclusion . Patient global assessment is a valid and responsive descriptor of overall effect in r and omized controlled trials of treatment for chronic low back pain", "Study Design . A cross-cultural adaptation and cross-sectional study of a sample of lumbar spine patients , with a sub sample followed prospect ively for retest reliability . Objectives . To assess the Italian version instrument reliability and validity . Summary of Background Data . The orthopaedic outcome measurements have been usually focused on objective parameters as radiograph measures or other technical aspects . However , these parameters are weakly related with outcomes that are more relevant to patients as functional status and symptoms . In the last ten years , the patient-oriented measures have become an important aspect of spinal clinical outcome evaluation . The most common instruments to assess patient perspective are self-administered question naires that must be vali date d by a widely accepted process to evaluate reliability and validity , which are fundamental for every instrumental measure . Methods . The North American Spine Society ( NASS ) question naire was culturally adapted for Italian-speaking people following the Guillemin criteria . The Italian version was tested on 74 consecutive patients who were referred to the authors ’ department and suffered from low back pain with leg irradiation . The results were compared with other vali date d patient-oriented measures . Forty-eight-hour retests were performed on a sub sample of 45 patients . Results . The question naire was favorably accepted by patients . The lumbar spine pain and disability and neurogenic symptoms subscales showed a high correlation with other patient-oriented measures , as hypothesized , and it also showed good values on test-retest . Conclusions . The question naire should be considered for patient health status monitoring and for clinical trials", "Study Design . A prospect i ve cohort design was used to evaluate the Functional Rating Index in a multicentered setting with 139 participants . The Functional Rating Index is a self-reporting instrument consisting of 10 items , each with 5 possible responses that express graduating degrees of disability . Objectives . The goal of this study was to evaluate the psychometric qualities of the Functional Rating Index . Summary of Background Data . The Functional Rating Index combines the concepts of the Oswestry Low Back Disability Question naire and the Neck Disability Index and seeks to improve on clinical utility ( time required for administration ) . Methods . One hundred thirty-nine subjects with spinal complaints participated in four different cohorts to study reliability , validity , responsiveness , and clinical utility . Results . Reliability : Test-retest : Intraclass correlation coefficient was excellent ( ICC3,k = 0.99 ) ; interitem correlation : Item efficiency was good , ranging between 0.54 and 0.82 , with a moderate correlation among all items ; Cronbach ’s alpha was excellent ( 0.92 ) . Validity : construct : The Functional Rating Index correlated with the Disability Rating Index ( 0.76 ) , the Short Form-12 Physical Component Score ( 0.76 ) , and the Short Form-12 Mental Component Score ( 0.36 ) . Responsiveness : Overall , the size effect was 1.24 , which is commendable . Clinical utility : Time required by the patient and staff averaged 78 seconds per administration , which is noteworthy . Effect of Sociodemographics : Total scores were not affected by education , gender , nor age , suggesting minimal external validity bias . Conclusions . The Functional Rating Index appears to be psychometrically sound with regard to reliability , validity , and responsiveness and is clearly superior to other instruments with regard to clinical utility . The Functional Rating Index is a promising useful instrument in the assessment of spinal conditions", "Study Design . A prospect i ve consecutive cohort study of patients with cervical spine pain and patients with lumbar spine pain referred to an academic medical center . Objectives . To investigate the presence of fear-avoidance beliefs in a sample of patients with cervical spine pain and to compare the association of pain intensity , disability , and fear-avoidance beliefs in patients with cervical spine pain with that in patients with lumbar spine pain . Summary of Background Data . Fear-avoidance beliefs are a specific psychosocial variable involved in the development of disability from low back pain . Psychosocial variables are believed to play a role in cervical disability , but specific variables have not been investigated . Methods . Consecutive patients referred to a multidisciplinary center completed self-reports of disability , pain intensity , and fear-avoidance beliefs during an initial evaluation session . Gender , type of symptom onset , acuity , and payer source were also recorded . Associations between disability , pain intensity , and fear-avoidance beliefs were investigated in patients with cervical spine pain and patients with lumbar spine pain . Results . In all , 163 patients completed the self-reports and were included in this study . Weaker relations between fear-avoidance beliefs and disability were found in patients with cervical pain than in those with lumbar pain . Significant differences in fear-avoidance beliefs were found for gender , type of symptom onset , and payer source ( workers ’ compensation , auto insurance , and traditional insurance ) . Conclusion . The associations among fear-avoidance beliefs , pain intensity , and disability differed between patients with cervical spine pain and patients with lumbar spine pain . Fear-avoidance beliefs were significantly different in subgroups of patients", "Abstract The General Function Score ( GFS ) is a disease-specific instrument consisting of nine items focusing on strict physical activities of daily living . It is intended as an alternative to the more complex scores of disability ( such as the Oswestry Disability Index ) , serving as a complement to the quality of life instruments in the study of low back pain ( LBP ) . It was developed from an original 17-item question naire , of which 11 of the items were tested for criterion validity in an observer-supervised performance test . Two items were excluded from further analysis because of too low a validity . The remaining nine-item GFS was tested for construct validity , reliability , feasibility and responsiveness in six different cohorts : 297 patients with chronic low back pain ( cohort 1 ) , an age- and sex-matched control group of 287 r and omly allocated Swedish citizens ( cohort 2 ) , three separate groups of patients admitted for surgery due to low back disorders ( cohorts 3–5 ) and out patients with spinal disorders ( cohort 6 ) . Correlations were tested with the Spearman Rank correlation coefficient , differences between groups with the Mann-Whitney test and the internal consistency with the Cronbach 's coefficient α . The GFS total scores showed correlations of 0.78 , 0.81 and 0.88 in the three aspects of the performance test . The response rate was 98.3–100 % . The mean time to complete the question naire was 1.2 min . The internal consistency was 0.69 and 0.86 in cohorts 1 and 2 respectively . The test-retest correlation was 0.88 . The GFS showed a high responsiveness to difference and change . The effect size was 0.82–0.96 in surgically treated disc herniation and 0.55–0.85 in spondylolisthesis . The GFS is a highly valid and reliable instrument with good responsiveness and feasibility , useful for evaluation of physical disability", "STUDY DESIGN A 2-year prospect i ve inception cohort study of back injury in nurses . OBJECTIVES To determine the extent to which characteristics of nurses , of the injury , and of the workplace predict occurrence and duration of time loss from work after back injury . SUMMARY OF BACKGROUND DATA During 2 years , 320 nurses incurred 416 back injuries at a large teaching hospital in Winnipeg , Canada . Nurses injured on preselected wards were targeted for early intervention , including provision of modified work , whereas nurses injured on other wards received the usual care . METHODS Time loss attributable to the back injury during the 6 months after injury was analyzed . Three statistical models were used to examine occurrence of time loss ( logistic regression ) , duration of time loss ( Tobit regression ) , and duration of time loss once an injury incurring time loss had been documented ( least-squares regression ) . RESULTS In 218 of the 416 injuries , the injured nurse consented to interview . Whereas perceived disability was related to whether a time loss injury would ensue , self-reported pain was strongly related to the duration of time loss once an injury had become a time loss injury . Duration of time loss was reduced by participation in the return-to-work program . Mechanism of injury , specifically injury occurring while lifting patients , result ed in greater time loss . CONCLUSIONS Focusing on reducing the perception of disability at the time of injury is critical to preventing time loss , but once time loss has occurred , offer of modified work and attention to pain reduction are warranted . The findings add to the evidence that workplace-based intervention programs can be effective in reducing the morbidity result ing from back injury", "& NA ; This study compares the responsiveness of three instruments of functional status : two disease‐specific question naires ( Oswestry and Rol and Disability Question naires ) , and a patient‐specific method ( severity of the main complaint ) . We compared changes over time of functional status instruments with pain rated on a visual analog scale . Two strategies for evaluating the responsiveness in terms of sensitivity to change and specificity to change were used : effect size statistics and receiver‐operating characteristic method . We chose global perceived effect as external criterion . A cohort of 81 patients with non‐specific low back pain for at least 6 weeks assessed these measures before and after 5 weeks of treatment . According to the external criterion 38 patients improved . The results of both strategies were the same . All instruments were able to discriminate between improvement and non‐improvement . The effect size statistics of the instruments were higher in the improved group than in the non‐improved group . For each instrument the receiver‐operating characteristic curves showed some discriminative ability . The curves for the Rol and Question naire and pain were closer to the upper left than the curves for the other instruments . The sensitivity to change of the rating of Oswestry Question naire was lower than that of the other instruments . The main complaint was not very specific to change . The two strategies for evaluating the responsiveness were very useful and appeared to complement each other", "The present study focuses on the long-term prognosis of radiographically verified stenosis of the lower lumbar spine . The purpose here was to describe the outcome 12 years after radiographic diagnosis of spinal stenosis and to identify factors predicting disability after operative or conservative treatment . Data were compiled on 75 patients ( 43 men and 32 women ) with changes in functional myelography diagnostic for spinal stenosis . Their mean age at the interview 12 years later was 61 years . The sagittal diameter of the dural sac was measured from baseline myelographs at all intervertebral levels and was corrected for magnification . In the interview , subjective outcome assessment was obtained with a structured question naire , and the low-back disorder was scored using the Oswestry disability index . The sagittal diameter of the dural sac was severely stenotic ( disability , even when the effects of age , sex , therapy regimen , and body mass index were adjusted for . For moderate and severe stenosis , the adjusted mean Oswestry indices were 28.4 and 39.1 , respectively ( p = 0.01 ) . Therapy as such ( operative versus nonoperative ) did not significantly correlate with later disability . The radiographic severity of lumbar spinal stenosis predicts disability independently of therapy regimen . R and omized clinical trials are needed to establish the indications for surgical and conservative treatment . Radiographic severity of the stenosis should be considered as an effect-modifying or confounding factor in clinical trials and other studies focusing on the outcome of lumbar spinal stenosis", "The Low-Back Outcome Score has been devised as a new and accurate rating system for patients with low-back pain . Thirteen factors , such as pain , employment , sporting ability , rest required , and activities of daily living , were included ; subjective opinion was excluded . Pain and active pursuits were weighted . Presentation of the score as a question naire , excluding examination findings , eliminated both interobserver variation and observer variation with time . The score was applied retrospectively in a follow-up study of conservatively treated patients and was found to be more comprehensive and more discriminating than the Oswestry Disability Score , the Waddell Disability Rating , or the Waddell Physical impairment Rating . The Low-Back Outcome Score is recommended for further evaluation in future prospect i ve studies in low-back pain", "STUDY DESIGN A prospect i ve observational study on the use of the Aberdeen Low Back Pain Disability Scale . OBJECTIVE To evaluate the reliability , validity , and responsiveness of the Chinese adaptation of the Aberdeen Low Back Pain Scale in Chinese patients in Hong Kong who have back pain . SUMMARY OF BACKGROUND DATA Frontline clinicians , research ers , and health care managers in Hong Kong are urgently in need of a Chinese adaptation of a low back pain outcome measure that has been subjected to a rigorous process of psychometric and clinical testing . METHODS Four sample s with 473 consecutive adult patients with low back pain from six physiotherapy outpatient departments in Hong Kong who completed the Aberdeen Low Back Pain Scale were observed and measured at time points including the beginning physiotherapy ; 10 days , 3 weeks , and 6 weeks after physiotherapy ; and when discharged from treatment . RESULTS The test-retest reliability coefficient was 0.94 ( 0.94 in the original English version ; figures from the English version are reported in parentheses ) . The Cronbach alpha coefficient was 0.85 ( 0.80 ) . The Spearman correlation coefficient , when the Aberdeen score was correlated with that of a generic current 42-item question naire regarding the patient 's perceived health to establish cross-sectional construct validity , was 0.59 ( 0.36 - 0.66 , with the Short Form 36 scale ) . The effect sizes ( responsiveness ) at weeks 3 and 6 after treatment began were 0.59 and 0.81 , respectively ( a high of 0.62 reported in the English version ) . CONCLUSIONS The Chinese version of the Aberdeen Low Back Pain Disability Scale retained the high levels of reliability , validity , and responsiveness of the original English version when tested in Hong Kong in four sample s of Chinese patients with low back pain", "Low Back Pain Rating scale is an index scale which includes measurements of pain intensity , disability , and physical impairment . The scale was design ed to monitor the outcome of clinical trials of low back pain treatment . It has been vali date d in 58 patients following first-time discectomy . The scale rating can be rapidly carried out and requires no special aids . With slight modification it can be used in office and telephone interviews , as well as postal question naires . These modifications only slightly reduce the quantity of information gathered . In the study , a high rater agreement ( 97.7 % ) was found without level difference between two observers using the scale . The validation process included : construct validity , criterion-related validity and item bias , relative to Global Assessment s pronounced by the patient and an experienced clinician . Low Back Pain Rating scale hs been shown to be valid and reliable in the assessment of low back pain", "Abstract A new measure is presented , suitable for documenting severity and response to treatment in chronic low‐back pain syndromes . It is self‐administered and combines two pain and seven mobility items . These were selected from pre‐existing vali date d instruments on the basis of their sensitivity to change after treatment . Their Italian vali date d translation was adopted . The measure was administered to 32 chronic low‐back pain Italian patients , all refractory to previous conservative treatments . In most cases they presented with herniation or protrusion of 1–3 lumbar discs . Patients were treated with 3–6 sessions of autotraction over a 5‐ to 15‐day period . Scores on the scale were recorded at admission , discharge and follow‐up , 1–3 months after treatment . At discharge and at follow‐up , patients were asked if , overall , they felt improved , the same or worse . At follow‐up , 20 patients out of 32 reported overall improvement . Scalometric properties of the measure were tested using Rasch analysis . For admission and follow‐up , items followed a consistent hierarchical relationship along a unidimensional pain/disability variable , which is being called back illness . The items were not redundant , in that they spread well along a wide range of difficulty/severity . The hierarchy matched well with the expected expression of the conditions of the patients . A study was conducted on 34 chronic back pain patients , showing satisfactory test‐retest reliability . Depending on the various items , Cohen 's unweighted K ranged from 0.27 to 0.78 , with ten of the 11 items above the 0.45 level of acceptability , while intraclass correlation coefficients ranged from 0.42 to 0.89 . At follow‐up , changes in BACKILL of plus 15 % or more , with respect to admission , were consistent with patients ' reports of improvement in 19 out of 20 cases . Changes in BACKILL of less than 15 % were consistent with patients reports of being the same or worse in 11 out of 12 cases", "STUDY DESIGN A cross-sectional clinical study . OBJECTIVES To determine whether there are specific symptoms , signs , and functional disability associated with adult spondylolisthesis . SUMMARY OF BACKGROUND DATA In spite of the common occurrence of adult spondylolisthesis , the symptoms , signs , and disability associated with it have not been analyzed in a large , well-defined group of patients . METHODS The symptoms , signs , and disability of 111 consecutive patients with adult spondylolisthesis , before r and omized treatment with fusion or physiotherapy , were compared with those of 39 patients with nonspecific low back pain before lumbar fusion . The patients completed a question naire covering clinical history and symptoms and su bmi tted a pain drawing . The signs were documented . Functional disability and pain were quantified by 12-function and 2-pain visual analog scales , respectively . RESULTS Sixty-two percent of the patients reported low back pain as well as sciatica , 7 % sciatica only , and 31 % low back pain only . Specific signs were infrequent . A positive straight leg raising test result in 12 % and an L5 sensory disturbance in 13 % were the most common . The symptoms were similar in patients with spondylolisthesis and chronic low back pain , but the chronic low back pain group reported more functional disability . Patients with a nonorganic pain drawing ( widespread , nonspecific pain ) were more often blue collar workers ; were more often and longer on sick leave ; and reported reduced mental condition , sexual function , functional ability , and more pain than patients with an organic pain drawing ( localized , specific pain ) . CONCLUSIONS The clinical pattern and functional disability in adult spondylolisthesis and in low back pain of nonspecific origin are similar . Sciatica in adult spondylolisthesis is typically not associated with a positive straight leg raising test result", "Study Design . A prospect i ve test-retest study was conducted to investigate both new and follow-up patients with low back pain presenting to an orthopedic surgeon specializing in back pain . Objectives . To further vali date the internal consistency and test – retest reliability of the Low Back Outcome Score , and to compare these results with other condition-specific disability scales . Summary of Background Data . To be useful in clinical practice , health-specific question naires must demonstrate reliability and validity . Several disease-specific question naires for low back pain have been vali date d to different extents . Methods . In this study , 102 new and 42 follow-up patients consecutively attending a consultant clinic completed the Low Back Outcome Score on their visit , then again after an interval of 1 week in postal form . This instrument also was completed by 230 patients presenting to a physiotherapist . Results . A response rate of 90 % was achieved for the postal question naire . A test of internal consistency conducted with the study sample achieved a Cronbach alpha coefficient of 0.85 . Overall agreement for test – retest reliability was 84 % , and the reliability coefficient ( K ) reached a range of 0.51 to 0.86 ( P Bl and /Altman plot was calculated , demonstrating that only 5 % of patient scores change by more than 11.6 scale points between test and retest , which is not sufficient to change outcome categories . Conclusion . The Low Back Outcome Score appears to have good internal consistency and test – retest reliability for use in clinical practice", "Abstract Objective : To compare the effectiveness over three years of chiropractic and hospital outpatient management for low back pain . Design : R and omised allocation of patients to chiropractic or hospital outpatient management . Setting : Chiropractic clinics and hospital outpatient departments within reasonable travelling distance of each other in 11 centres . Subjects : 741 men and women aged 18 - 64 years with low back pain in whom manipulation was not contraindicated . Outcome measures : Change in total Oswestry question naire score and in score for pain and patient satisfaction with allocated treatment . Results : According to total Oswestry scores improvement in all patients at three years was about 29 % more in those treated by chiropractors than in those treated by the hospitals . The beneficial effect of chiropractic on pain was particularly clear . Those treated by chiropractors had more further treatments for back pain after the completion of trial treatment . Among both those initially referred from chiropractors and from hospitals more rated chiropractic helpful at three years than hospital management . Conclusions : At three years the results confirm the findings of an earlier report that when chiropractic or hospital therapists treat patients with low back pain as they would in day to day practice those treated by chiropractic derive more benefit and long term satisfaction than those treated by hospitals", "Quality of life has been defined as “ the extent to which our hopes and ambitions are matched by experience . ” To improve a patient 's quality of life through medical care would be to “ narrow the gap between a patient 's hopes and expectations and what actually happens . ” Using the above definition as a conceptual basis , we produced a self-administered , Patient-Generated Index ( PGI ) of quality of life . The PGI was completed by 359 patients presenting with low back pain . The validity of the measure was assessed by correlating patients ' PGI scores with a well-vali date d health profile , the Short-Form 36-item Health Survey ( SF-36 ) , and with their scores on a clinical back pain question naire . Stepwise multiple regression was then used to model the relationship between the PGI score and the SF-36 . Patients ' PGI scores showed a high correlation with SF-36 scales measuring pain , social functioning , and role limitations attributable to physical problems , and with the clinical question naire . Together with whether a person was retired or not , these health variables were able to explain 25 % of the variance in PGI scores . Patient generated index scores were significantly lower in patients referred to hospital compared with those managed solely in general practice and tended to reflect the general practitioner 's assessment of symptom severity . We conclude that it is possible to construct a question naire that quantifies the effect of a medical condition on patients ' quality of life in a way that has meaning and relevance in the context of their daily lives . The PGI has considerable potential for routine use in a wide range of clinical conditions for which the measurement of outcome has hitherto proved very difficult", "STUDY DESIGN A prospect i ve , consecutive study of patients ' outcome at three subsequent follow-up times after lumbar disc surgery . OBJECTIVES To evaluate how consistent outcome remained in a group of patients after lumbar disc surgery . SUMMARY OF BACKGROUND DATA Despite similar results concerning the overall outcome , results in most studies show different prognostic factors for lumbar disc surgery at different follow-up times . A reason for this observation could be that patients shift to a different outcome group during the observation period . METHODS Before surgery and at the three follow-ups ( 3 , 12 , and 28 months after surgery ) the Low Back Outcome Score was calculated . Groups with favorable and unfavorable outcome were determined after each follow-up according to the scores . RESULTS Ninety-eight patients were studied . Forty percent showed an unstable outcome at different follow-up times . For each follow-up , three prognostic factors were determined . No prognostic factor showed significance at all follow-up examinations . CONCLUSIONS Patients whose outcome after lumbar disc surgery does not remain stable present a major problem in the calculation of prognostic factors", "Study Design A prospect i ve cohort study of patients seen in primary care for low back pain . Objectives A new measure of back pain outcomes is used to describe the status of back problems at various intervals after visits to primary care physicians and to identify subsets of patients with worse prognoses . Summary of Background Data Most previous studies of the prognosis of back pain in primary care have failed to provide clinical ly useful information . Methods Baseline data were collected from 219 patients making an initial visit for an episode of low back pain to a primary care clinic . A measure of how patients reported they would feel if they had their current back symptoms for the rest of their lives ( “ Symptoms Satisfaction ” ) was used to distinguish good from poor outcomes . Patient outcomes were assessed 1 , 3 , 7 , and 52 weeks after the index visit . Results Only 67 % of patients reported good outcomes after 7 weeks , and only 71 % were satisfied with their condition 1 year later . After controlling for the effects of other variables measured during the initial physician visit , only younger age , depression , and pain below the knee were significant predictors of poor outcome at 7 weeks , and only pain below the knee and depression were significant predictors at 1 year . Conclusions The proportion of primary care patients with back pain who have poor outcomes appears to be higher than generally recognized . Ways of improving how primary care responds to patients with persisting pain should be investigated", "Study Design . A r and omized controlled trial comparing usual care with a program for the coordination of primary health care ( CORE ) for the treatment of subacute low-back pain patients . Objectives . To measure the effectiveness of the CORE program as a mean for implementing clinical practice guidelines for low-back pain in an urban community . Summary of Background Data . Clinical practice guidelines have been developed for primary care physicians and patients on the clinical management of low-back pain . The implementation of the guidelines in a large community is difficult with the multiplicity of medical and nonmedical back care providers and products . The CORE program was design ed to make the guidelines fit in this complex environment . Methods . One hundred ten workers compensated for low-back pain for 4 to 8 weeks in metropolitan Montreal were r and omized in two groups : usual care ( N=56 ) and the CORE program ( N=54 ) . Coordination of primary health care was performed by two primary care physicians and a nurse in liaison with the treating physicians , and included a complete examination , recommendations for the clinical management , and support to carry out the recommendations . All workers were followed for 6 months . Back pain and functional status were assessed at baseline , 3 months , and 6 months . Results . In the 6-month follow-up , the CORE group returned to work 6.6 days ( st and ard error = 8.9 ) quicker than the control group , a difference that was not statistically significant . However , the CORE group showed a sustained improvement in pain and functional status with two-fold differences at the end of the 6 months of follow-up . This represented nine points on the Oswestry scale ( P = 0.02 ) and 12 points on the Quebec Back Pain Disability Scale ( P = 0.01 ) . The CORE group also used three times less specialized imaging tests of the spine at 3 months ( P workers with low-back pain could be improved by implementing the clinical practice guidelines with primary care physicians in a large community , without delaying the return to work . The CORE intervention for back pain patients ishighly relevant to primary care practice . It is simple in its application , flexible to accommo date physicians ’ and patients ’ preferences in health care , and it is effective on patients ’ clinical outcome", "There is growing evidence for the idea that in back pain patients , pain-related fear ( fear of pain/physical activity/(re)injury ) may be more disabling than pain itself . A number of question naires have been developed to quantify pain-related fears , including the Fear-Avoidance Beliefs Question naire ( FABQ ) , the Tampa Scale for Kinesiophobia ( TSK ) , and the Pain Anxiety Symptoms Scale ( PASS ) . A total of 104 patients , presenting to a rehabilitation center or a comprehensive pain clinic with chronic low back pain were studied in three independent studies aim ed at ( 1 ) replicating that pain-related fear is more disabling than pain itself ( 2 ) investigating the association between pain-related fear and poor behavioral performance and ( 3 ) investigating whether pain-related fear measures are better predictors of disability and behavioral performance than measures of general negative affect or general negative pain beliefs ( e.g. pain catastrophizing ) . All three studies showed similar results . Highest correlations were found among the pain-related fear measures and measures of self-reported disability and behavioral performance . Even when controlling for sociodemographics , multiple regression analyses revealed that the subscales of the FABQ and the TSK were superior in predicting self-reported disability and poor behavioral performance . The PASS appeared more strongly associated with pain catastrophizing and negative affect , and was less predictive of pain disability and behavioral performance . Implication s for chronic back pain assessment , prevention and treatment are discussed", "To identify predictors of back-related long-term functional limitations , 1213 adult enrollees of a Health Maintenance Organization ( HMO ) in Washington state were interviewed about a month after a consultation for back pain in a primary care setting in 1989 - 1990 , and followed each year thereafter . Out of 100 factors documented at the one-month assessment , measures of somatization , depression , functional limitations , and pain were the strongest predictors of two-year modified Rol and -Morris score among a r and om sub sample of 569 subjects . A multiple regression model containing the Symptom Checklist Depression and Somatization scores , the one-month modified Rol and -Morris score and the number of pain days in the past six months explained about 30 % of the variance in the outcome . Using recursive partitioning , a very simple model was developed to identify patients at high risk of sustaining long-term significant functional limitations . The regression model and the recursive partitioning model were successfully tested in a fresh sample of patients ( n = 644 ) . Clinical application of the recursive partitioning model and method ological aspects of this study are discussed", "A prospect i ve study was set up to evaluate the influence of psychological distress on the outcome of lumbosacral fusion in a group of chronic low back pain ( CLBP ) patients . Response to low back surgical procedures depends upon physical and psychological factors . Various reports exist concerning the influence of a patient 's psychological condition on the outcome of low back surgery . Few investigators , however , have checked this influence in a prospect i ve manner . A psychogenic back pain score ( NPL ) was administered to 53 CLBP patients ( 24 men and 29 women ) prior to surgery , to evaluate the presence of psychological distress . According to the test score patients were divided in an \" organic \" , an \" uncertain \" and a \" psychogenic \" group . Disability in activities of daily living result ing from the back pain was also scored preoperatively with the Oswestry Disability Index ( ODI ) . Twelve months after surgery the ODI was readministered to the 50 patients available to follow-up . Each group separately showed significant improvement of disability 12 months after fusion , however , the \" organic \" group scored significantly better than the \" psychogenic \" group . Question naires about back pain , sciatic pain and use of analgesics and Visual Analog Scales regarding pain and disability also indicated better results in the \" organic \" group . Psychological distress deteriorates the subjective outcome of lumbosacral spine fusion and psychological screening should indeed be an integral part of the global assessment of CLBP patients , especially when surgery is considered" ]	41189910-06ff-11f0-808a-c43d1ab1c353
Objective A secondary analysis of a systematic review on interventions to improve osteoporosis ( OP ) investigation and treatment was conducted to examine reported key outcomes : ( 1 ) the cost of the intervention ; ( 2 ) the proportion of patients taking OP medication beyond 6 months of the intervention ; and ( 3 ) the proportion of patients who re-fractured . Methods Fifty-seven articles reporting on 54 studies ( 64 interventions ) from 11 countries were included . Intervention studies to improve OP management were eligible if they were conducted in an orthopedic setting and included primary data on ≥20 patients presenting with a hip fracture or any fragility fracture . To compare outcome data across all interventions regardless of study design , an equated proportion ( EP ) using a denominator based on the intention-to-treat principle was derived . Whether a cost analysis had been conducted , the EP of patients who were taking medication beyond 6 months of the intervention , and the EP of patients who re-fractured during the study period were documented . Results Of the 54 studies , 2 reported a cost analysis and demonstrated that the interventions were at least cost-effective . The EP for medication use beyond 6 months of the intervention ranged from 17 to 56 % for four studies . The EP for re-fracture ranged from 0 to 5 % for four studies . Conclusion Most interventions did not report key outcomes . In addition , authors used varying time frames for re-fracture and medication use , making direct comparisons impossible . Authors should consider including intervention costs , medication use beyond 6 months of the intervention , and re-fracture data in future fracture secondary prevention programs	[ "Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items", "Objectives To establish a protocol for the treatment of fragility fractures in the hospital setting based on treatment of osteoporosis . Material s and methods An intervention protocol was implemented in patients with fragility fractures based on ( 1 ) indicating the diagnosis of osteoporotic fracture in the summary of discharge ; ( 2 ) “ lifestyle recommendations ” ; and ( 3 ) therapy for osteoporosis . Thirty-one hospitals were involved and they were informed of the importance of protocol compliance . In the first phase , a retrospective study was conducted to establish the number of low-energy fractures treated and the percentage of them that had complied with the protocol ( n = 887 ) . Then , prospect ively , the same data were collected for the patients managed for 1 year ( n = 6,826 ) in three sections of 4-month intervals . Results The percentage of compliance increased from 8.2 to 57.2 % in the first point , from 12.6 to 42.4 % in the second , and from 10.3 to 43.2 % in the third . Conclusion The implementation of programs to improve osteoporosis treatment is very useful for ensuring adherence in the management of osteoporosis following admission due to fragility fracture", "BACKGROUND Although osteoporosis is strongly associated with hip fractures , the initiation of osteoporosis treatment following hip fractures occurs at surprisingly low rates of between 5 % and 30 % . Currently , most patients receiving treatment have been referred back to their primary care physician for osteoporosis management . The purpose of this study was to compare the effect of osteoporosis management initiated by the orthopaedic team and osteoporosis management initiated by the primary care physician on the rates of treatment at six months . METHODS A prospect i ve r and omized trial was conducted to assess the difference in the rate of osteoporosis treatment when an in-house assessment of osteoporosis was initiated by the orthopaedic surgeon and follow-up was conducted in a specialized orthopaedic osteoporosis clinic compared with osteoporosis education and \" usual \" care . RESULTS Sixty-two patients were enrolled in the study . Thirty-one patients each were in the control and intervention groups . The percentage of patients who were on pharmacologic treatment for osteoporosis at six months after the fracture was significantly greater when the evaluation was initiated by the orthopaedic surgeon and was managed in a specialized orthopaedic osteoporosis clinic ( 58 % ) than when treatment was managed by a primary care physician ( 29 % ) ( p = 0.04 ) . CONCLUSIONS An active role by orthopaedic surgeons in the management of osteoporosis improves the rate of treatment at six months following a hip fracture", "BACKGROUND In a r and omized trial of patients with hip fractures , we previously demonstrated that a hospital-based case manager could increase rates of appropriate osteoporosis treatment to 51 % compared with 22 % for usual care ( P Patients with hip fractures were r and omized to usual care ( n = 110 ) or a case manager ( n = 110 ) and followed up for 1 year . Time-motion studies were used to determine intervention costs . From a third-party health care payer perspective and over the patient 's remaining lifetime , a Markov decision-analytic model was constructed to determine cost-effectiveness of the intervention compared with usual care . Costs and benefits were discounted at 3 % and expressed in 2006 Canadian dollars . RESULTS The intervention cost CaD $ 56 per patient . Compared with usual care , the intervention strategy was dominant : for every 100 patients case managed , 6 fractures ( 4 hip fractures ) were prevented , 4 quality -adjusted life-years were gained , and CaD $ 260 000 was saved by the health care system . Irrespective of the number of patients case managed , the intervention reached a break-even threshold within 2 years . The intervention dominated usual care over the entire spectrum of 1-way sensitivity analyses and was cost-saving in 82 % of probabilistic model simulations . CONCLUSIONS Compared with usual care , we found that using a case manager for patients with hip fractures increased rates of appropriate osteoporosis treatment . The intervention dominated usual care , and the analysis suggests that systems implementing an intervention similar to ours should expect to see a reduction in fractures , gains in life expectancy , and substantial cost savings . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00175175", "Background : Osteoporosis is a common disease characterized by decreased bone mass and increased fracture risk in postmenopausal women and the elderly . Hip fractures are among the most common consequences of osteoporosis and unfortunately usually occur late in the course of the disease . When a patient is admitted to the hospital with a fragility hip fracture , a unique opportunity for diagnosis and treatment presents itself . Fortunately , several medications have proven to be effective in lowering the risk of future fractures . The purpose s of the present study were to test the hypothesis that most fragility hip fractures go untreated and to determine whether educational efforts to raise physician awareness have led to an improvement in osteoporosis treatment rates . Methods : A retrospective cohort study was performed with use of the patient data bases at two university medical centers and one university-affiliated community hospital . The charts of 300 r and omly selected patients were sorted with use of ICD-9 ( International Classification of Diseases , Ninth Revision ) codes for femoral neck fractures . There were 100 patients from each center , with twenty-five patients from each year between 1997 and 2000 . The admitting diagnosis , mechanism of injury , admission medications , procedures performed during hospitalization , and discharge medications were then extracted and analyzed . During this period , the National Osteoporosis Foundation established guiding principles for the treatment of fragility fractures . Results : Of the seventy-five patients from all centers for each year from 1997 to 2000 , 11 % , 13 % , 24 % , and 29 % , respectively , were discharged with a prescription for some medication targeting osteopenia , either supplemental calcium or an antiosteoporotic medication ( estrogen , calcitonin , a bisphosphonate , or raloxifene ) . A trended chi-square analysis of this increase revealed a p value of prescription at the time of discharge . However , forty of these patients ( 13.3 % of the overall group ) received calcium and only eighteen ( 6.0 % of the overall group ) received a medication to actively prevent bone resorption and treat osteoporosis . In addition , no patient underwent a bone density scan while in the hospital . Conclusions : Elderly patients and postmenopausal women who are admitted to the hospital and diagnosed with a low-energy femoral neck fracture have been undertreated for osteoporosis . However , over the four years of the present study , there was a significant increase in the rate of treatment . It is hoped that treatment rates will continue to increase in the future with continued educational efforts", "Background : Missed opportunities for osteoporosis detection and treatment following fractures , especially in the elderly , are common . Clinical pharmacy specialist ( CPS ) intervention may positively impact this deficiency . Objective : To examine the impact of a CPS-managed intervention to identify , screen , and initiate appropriate osteoporosis pharmacotherapy in elderly patients after an atraumatic fracture . Methods : This was a prospect i ve quality improvement analysis . Hospitalized and ambulatory patients who had a diagnosis of atraumatic fracture between July 2002 through August 2003 but were not on osteoporosis pharmacotherapy were identified by CPSs . Bone mineral density ( BMD ) screening and osteoporosis pharmacotherapy recommendations were made by a CPS when appropriate . Descriptive analyses were performed to determine the proportion of patients initiated on osteoporosis pharmacotherapy or receiving a recommended BMD evaluation . Results : A total of 137 ( 40 inpatient and 97 ambulatory ) female patients were included . The mean ages ± SD of inpatient and ambulatory patients were 83 ± 8 and 70 ± 7 years , respectively . Overall , 50 % ( n = 69 ) of patients either initiated their recommended osteoporosis pharmacotherapy ( 48 % [ n = 19 ] and 30 % [ n = 29 ] of inpatient and ambulatory patients , respectively ) or received a recommended BMD screening ( 42 ambulatory patients were recommended and 50 % [ n = 21 ] completed a BMD test ) . Of the patients who completed a BMD test , 17 ( 81 % ) were osteoporotic . All 17 were initiated on osteoporosis pharmacotherapy . Conclusions : Using a systematic approach to identify patients in need of osteoporosis pharmacotherapy , a CPS-managed intervention result ed in clinical ly meaningful osteoporosis treatment initiation rates ", "Introduction Older patients with fragility fractures are not commonly tested or treated for osteoporosis . Compared to usual care , a previously reported intervention led to 30 % absolute increases in osteoporosis treatment within 6 months of wrist fracture . Our objective was to examine longer-term outcomes , reproducibility , and cost-effectiveness of this intervention . Methods We conducted an extended analysis of a non-r and omized controlled trial with blinded ascertainment of outcomes that compared a multifaceted intervention to usual care controls . Patients > 50 years with a wrist fracture treated in two Emergency Departments in the province of Alberta , Canada were included ; those already treated for osteoporosis were excluded . Overall , 102 patients participated in this study ( 55 intervention and 47 controls ; median age : 66 years ; 78 % were women ) . The interventions consisted of faxed physician reminders that contained osteoporosis treatment guidelines endorsed by opinion leaders and patient counseling . Controls received usual care ; at 6-months post-fracture , when the original trial was completed , all controls were crossed-over to intervention . The main outcomes were rates of osteoporosis testing and treatment within 6 months ( original study ) and 1 year ( delayed intervention ) of fracture , and 1-year persistence with treatments started . From the perspective of the healthcare payer , the cost-effectiveness ( using a Markov decision-analytic model ) of the intervention was compared with usual care over a lifetime horizon . Results Overall , 40 % of the intervention patients ( vs. 10 % of the controls ) started treatment within 6 months post-fracture , and 82 % ( 95%CI : 67–96 % ) had persisted with it at 1-year post-fracture . Delaying the intervention to controls for 6 months still led to equivalent rates of bone mineral density ( BMD ) testing ( 64 vs. 60 % in the original study ; p = 0.72 ) and osteoporosis treatment ( 43 vs. 40 % ; p = 0.77 ) as previously reported . Compared with usual care , the intervention strategy was dominant – per patient , it led to a $ 13 Canadian ( U.S. $ 9 ) cost savings and a gain of 0.012 quality -adjusted life years . Base-case results were most sensitive to assumptions about treatment cost ; for example , a 50 % increase in the price of osteoporosis medication led to an incremental cost-effectiveness ratio of $ 24,250 Canadian ( U.S. $ 17,218 ) per quality -adjusted life year gained . Conclusions A pragmatic intervention directed at patients and physicians led to substantial improvements in osteoporosis treatment , even when delivered 6-months post-fracture . From the healthcare payer ’s perspective , the intervention appears to have led to both cost-savings and gains in life expectancy", "In an attempt to identify a high-risk cohort of patients , who could be offered preventive therapy , we assessed patients who had suffered one hip fracture . A total of 394 patients were prospect ively followed to determine those who had suffered a second fracture . Entry bone mass of the unfractured hip and total body was examined by dual X-ray absorptiometry ( DXA ) and of the os calcis , by quantitative ultrasound ( QUS ) , along with various clinical parameters . The relative risks in the QUS parameters did not reach significance , except for broadb and ultrasound attentuation as measured by the McCue CUBA Clinical , whereas femoral neck and total body bone mineral density also reached significance . Lowest quartile body weight was also a significant risk factor as were occurrence of a new fall and poor mobility score . Using Receiver Operator Characteristic curves , we found no significant differences between DXA trochanter or for the Mini Mental State Examination score in predicting those who sustained a second hip fracture . In this elderly group risk factors are almost as good as bone mass at predicting those who will sustain a second hip fracture . Low body weight and poor mobility could be used as triggers for the use of preventive therapy without the use of bone mass measurements and to target expensive preventive therapy to reduce fracture risk", "OBJECTIVE To review the 3-year performance of an established osteoporosis care service and consider further improvements in an effort to reduce fragility fractures . METHODS Osteoporosis care has been coordinated for all willing and able patients with orthopedic fragility fractures in our health system by a nurse and medical director since 2003 , using a guideline -based care algorithm and task management software . Patients were followed by telephone for 2 years to monitor their status and optimize adherence to treatment . Demographics , management recommendations , clinical data , and adherence to treatment were review ed for the 2003 - 2005 patient population . RESULTS Of 1,019 patients with fragility fractures , 61 % underwent osteoporosis evaluation and treatment . The remainder included 15 % who refused to participate and 24 % who were unable to participate for various logistical and health reasons . More patients age > 80 years were unwilling or unable to participate . Bone densities ( dual x-ray absorptiometry [ DXA ] ) were normal , low , or osteoporotic in 24 % , 55 % , and 21 % of patients , respectively , and 60 % of the osteoporotic group had > or = 1 abnormal metabolic bone laboratory result . Only 17 % of the total reported a previous fracture , and 47 % had ever undergone DXA . Few experienced bone loss , a new fracture , or bisphosphonate intolerance during treatment . CONCLUSION An osteoporosis care service has coordinated care for every willing and able fragility fracture patient with positive outcomes . In addition , the results suggest a high priority for earlier proactive diagnosis and intervention of the at-risk population if fractures are to be reduced", "This study compares the investigation of and treatment for osteoporosis in two groups of fracture patients at two orthopaedic centres in the UK . One centre had a formal fracture liaison service ( FLS ) responsible for screening fracture patients for osteoporosis . The other centre relied upon individual clinicians to initiate investigation or treatment for osteoporosis in patients following fracture . Patients who had been treated in either centre for a proximal humeral or hip fracture during a 6-month period were followed up 6 months later to identify how many had received screening or treatment for osteoporosis . Information was retrieved from a prospect ively compiled data base or by postal question naire . The study revealed that in the centre with an FLS 85 % of patients with a proximal humeral fracture and 20 % with a hip fracture had been offered a dual-energy X-ray absorptiometry ( DEXA ) scan . Approximately 50 % and 85 % , respectively , were receiving treatment for osteoporosis 6 months following their fracture . This compared with DEXA being offered to only 6 % and 9.7 % of humeral and hip fracture patients , respectively , and 20 % ( hip ) and 27 % ( proximal humerus ) receiving osteoporosis treatment in the other centre . The presence of an FLS result ed in a considerably higher proportion of patients receiving investigation and treatment for osteoporosis following a hip or proximal humeral fracture", "UNLABELLED A low-impact fracture in a postmenopausal woman should prompt investigations for osteoporosis followed , if needed , by appropriate treatment . OBJECTIVES To evaluate the impact of information alerting general practitioners to the need for osteoporosis treatment in postmenopausal women with a recent history of peripheral fracture . METHODS We conducted a prospect i ve 7-month follow-up study of 78 postmenopausal women , with a mean age of 81.5 years , admitted to the emergency department for peripheral fractures . Three months after the fracture , we sent a letter to the general practitioner of each patient emphasizing the probable contribution of osteoporosis to the fracture and the need for osteoporosis treatment . Six months after the fracture , we interviewed the patients by telephone , and one month later we mailed a question naire to those physicians who had not followed the treatment recommendation . RESULTS At emergency room admission , 9 patients were receiving treatment for osteoporosis ( hormone replacement therapy in one patient and calcium and vitamin D supplementation in eight patients ) . Admission to a ward was required in 66 ( 85 % ) patients . No treatment for osteoporosis was given at discharge . Six months after discharge , seven patients reported recent initiation of calcium and vitamin D supplementation , and none reported other osteoporosis treatments . The response rate to the physician question naire mailed 7 months after discharge was 54 % ( n=28 ) ; responses showed treatment of 11 additional patients , by calcium and vitamin D supplementation in six cases and by bisphosphonates with or without calcium and vitamin D supplementation in five cases . Treatment initiation rates were similar in patients younger and older than 80 years . CONCLUSIONS Despite information of general practitioners about the need for osteoporosis treatment , such treatment was initiated in only 30.5 % of patients . General practitioners may be reluctant to initiate osteoporosis treatment in patients who are very old or have multiple comorbidities", "OBJECTIVES Osteoporosis treatment rates after a fracture are low . This study evaluated methods to increase guideline -recommended osteoporosis care postfracture . DESIGN Participants were r and omly assigned to usual care or one of two interventions . Analysis of primary outcomes used electronic data and linear regression . SETTING A Pacific Northwest nonprofit health maintenance organization . PARTICIPANTS Female patients aged 50 to 89 who suffered a fracture in 1999 and had not received bone mineral density ( BMD ) measurement or medication for osteoporosis ( n=311 ) and their primary care providers ( n=159 ) . INTERVENTION Patient-specific clinical guideline advice to the primary care provider delivered by electronic medical record ( EMR ) message or electronic reminder to the provider plus an educational letter mailed to the patient . MEASUREMENTS BMD measurement and osteoporosis medication . RESULTS At 6 months , provider reminder result ed in 51.5 % of patients receiving BMD measurement or osteoporosis medication , provider reminder plus patient education result ed in 43.1 % , and usual care result ed in 5.9 % ( P Patients aged 60 to 69 were 18 % ( 95 % confidence interval=3 - 34 ) more likely to receive BMD measurement or an osteoporosis medication than those aged 80 to 89 . CONCLUSION Patient-specific postfracture advice to the provider through an EMR message significantly increased BMD measurement and osteoporosis medication . As EMRs become more widespread , this intervention could improve osteoporosis management for many postfracture patients . Future research should identify barriers to and facilitators of care for older , high-risk patients", "Introduction Despite the high risk for subsequent fracture following an initial osteoporotic fracture , the majority of subjects with minimal trauma fractures receive no treatment for osteoporosis . The primary aim of this investigation was to determine whether an information-based intervention could change post-fracture management of osteoporosis . A secondary aim was to define participant- and doctor-related barriers to osteoporosis management . Methods Consecutive fracture patients ( n=254 ) from the outpatient fracture clinic at St Vincent ’s Hospital , Sydney were interviewed over a 15-month period ( February 2002–July 2003 ) . Fracture risk factors , prior investigation and treatment for osteoporosis were collected at baseline . Participants were initially contacted after 3 months to ascertain follow-up management . All those not investigated or treated by their primary care physician were then r and omized to either a personalized letter or the same letter plus an offer of a free bone mineral density ( BMD ) test . Participants were contacted after 9 months to record further investigations or treatment for osteoporosis . Results Less than 20 % of the participants had a primary care physician follow-up 3 months after the fracture , leaving 159 who were r and omized to a personalized letter ( n=79 ) and a personalized letter plus the offer of a free BMD test ( n=80 ) . There was a significant increase in the number of people investigated for osteoporosis in the group receiving the letter plus BMD offer [ 38 % ( letter + BMD ) vs. 7 % ( letter only ) ; p=0.001 ) . A high proportion of those tested had low BMD ( 49 % osteopenia and 17 % osteoporosis ) . However , the rates of treatment in both groups were very low ( 6 % ) . Furthermore , even among the few individuals ( 23 % ) who contacted their primary care physician , only 25 % were recommended treatment . The belief that the fracture was osteoporotic was an independent predictor of having a BMD test , a primary care physician follow-up and treatment . Other independent predictors were age over 50 years for a primary care physician follow-up , female sex for having a BMD test and having had a BMD test for treatment . Conclusion This study demonstrates that an information-based intervention led to a modest increase in the proportion of people investigated for osteoporosis ; however . there was no significant effect on treatment rates . The offer of a free BMD assessment was associated with a significantly higher rate of investigation than a personalized letter alone ( odds ratio : 8.5 ; 95 % confidence interval : 3.1–24.5 ) , but this investigation did not affect treatment rate . The low uptake of either a BMD or a visit to a primary care physician together with low rates of treatment recommendation even among people who contacted their primary care physician reflects significant participant and doctor-related barriers to osteoporosis management", "Summary In a cluster r and omized trial , we evaluated the effect of a multifaceted intervention ( directed at both patient and primary care physician ) on the rates of testing and treatment of osteoporosis in postmenopausal women within six months of their wrist fracture . Compared to usual care , women in the intervention practice s were three times more likely to receive bone mineral density testing and prescribed osteoporosis treatments . Introduction Postmenopausal women with wrist fractures are at increased risk of future fragility fractures , yet they frequently do not receive evaluation and treatment for osteoporosis . We set out to evaluate a multifaceted intervention design ed to improve management of osteoporosis in older women with recent wrist fractures . Methods Cluster r and omized trial of 270 women cared for in 119 primary care practice s. We recruited postmenopausal women with an acute wrist fracture from the emergency departments of hospitals in southeastern Ontario , Canada . Family practice s were r and omly assigned to either the intervention or usual care . The intervention consisted of a mailed reminder with a summary of treatment guidelines and letter sent to the primary care physician , in addition to an educational package and letter to the women . The primary outcome was the proportion of women prescribed osteoporosis therapy within 6 months of their fracture . Results The mean age of women was 69(10.9 ) years . The intervention increased the proportion of women started on osteoporosis medications ( 28 % vs. 10 % ) of controls , adjusted OR 3.45 , 95 % CI , 1.58–7.56 , p = 0.002 ) and the proportion who had a bone mineral density ( BMD ) test ( 53.3 % vs. 26 % ) of controls , OR 3.38 , 95 % CI , 1.83–6.26 , p testing and treatment rates . Conclusion A multifaceted intervention significantly improved rates of osteoporosis treatment and BMD testing in postmenopausal women with wrist fractures", "OBJECTIVE We aim ed to determine whether a novel Patient Empowerment and Physician Alerting ( PEPA ) intervention would improve the proportion of seniors who were investigated and treated for osteoporosis after hip fracture . METHODS We undertook a 6-month r and omized controlled trial ( RCT ) in 48 women and men > /= 60 years old who had suffered a hip fracture and were admitted to a tertiary-care university hospital . The primary outcome measure was the proportion of participants offered one or more osteoporosis-specific ' best practice s ' measured using the Diagnosis and Management Question naire ( DMQ ) . Participant responses were vali date d in part by physician report . RESULTS In the PEPA intervention group , 19 ( 68 % ) were offered one or more components of best practice care compared with 7 ( 35 % ) in the ' usual care ' group ( p PEPA group , 15 ( 54 % ) ( p bisphosphonate therapy , 8 ( 29 % ) ( p bone mineral density scan , 11 ( 39 % ) were prescribed calcium and vitamin D ( p = .32 ) , and 9 ( 32 % ) ( p exercise . In the usual care group , 0 ( 0 % ) were prescribed bisphosphonate therapy , a bone mineral density assessment , or exercise and 6 ( 30 % ) were prescribed calcium and vitamin D. CONCLUSIONS This simple , inexpensive PEPA intervention result ed in far superior clinical management than did usual care in a population at high risk of future hip fracture", "Context Many patients who sustain fragility fractures do not receive subsequent testing and treatment for osteoporosis . Contribution This study shows that faxed reminders to physicians , treatment guidelines endorsed by opinion leaders , and patient education about osteoporosis can increase the testing and therapy for osteoporosis among patients who present to an emergency department with wrist fracture . Caution s This study did not r and omly assign persons to the intervention group and did not examine improvements in bone density or repeated fractures . The Editors Osteoporosis , a chronic and progressive condition that leads to decreased bone mass and skeletal fragility , may result in fractures , disability , pain , deformity , and even death ( 1 - 3 ) . The condition is common , affecting an estimated 1.4 million Canadians and 10 million Americans ( 1 , 2 ) . These figures represent 25 % of women and 12 % of men older than 50 years of age ( 1 , 2 ) . In the United States , the annual cost of treating osteoporosis and its sequelae has been estimated at $ 13.8 billion ( 2 ) , compared with $ 7.5 billion for congestive heart failure and $ 6.2 billion for asthma ( 3 ) . Without better preventive strategies , the rate of osteoporotic fractures is expected to double over the next 15 years ( 4 ) . Several experts ( 5 ) and guidelines ( 1 , 2 ) suggest a preventive strategy of identifying people with typical osteoporosis-related fractures ( for example , fractures of the hip , spine , or wrist [ often called fragility fractures ] ) and targeting them for treatment . They recommend this strategy because this population is at the greatest risk for subsequent fracture and may derive the greatest absolute benefit from treatment . Numerous safe and effective treatments can reduce the risk for recurrent fracture by 40 % to 60 % ( 1 - 3 , 6 ) . In addition , with the use of bisphosphonates and raloxifene , all subgroups of examined patients may obtain beneficial effects ( 3 , 7 - 9 ) within a year ( 7 , 8) . People 50 years of age and older with a fracture of the wrist may be particularly well suited to a strategy of case finding and secondary prevention . Fractures of the wrist are the most common symptomatic fracture related to osteoporosis ( 3 ) , and 70 % to 80 % of persons with wrist fractures have low bone mass ( 10 , 11 ) . Observational studies suggest that a wrist fracture is a sentinel event in the natural history of osteoporosis because this type of fracture forecasts an increased risk for fractures of the hip and spine over the next 10 to 20 years ( 12 - 14 ) . Best practice ( clinical practice consistent with current evidence and expert consensus ) would be to identify people 50 years of age or older with a fragility fracture of the wrist , to measure their bone mineral density , and to treat those with low bone mass or osteoporosis ( 1 , 2 , 5 ) . However , the gap between best practice and everyday clinical practice is wide . Over the past 5 to 10 years , studies from the United States ( 3 , 15 , 16 ) , Canada ( 17 , 18 ) , and elsewhere ( 5 , 19 ) report that rates of testing for and treating osteoporosis a year or longer after a fracture of the wrist are less than 10 % to 20 % . This is an important failure in the process of knowledge translation and indicates that benefits within our reach are not being achieved . We design ed a pragmatic , multifaceted osteoporosis intervention strategy directed at people 50 years of age or older with a fracture of the wrist and at their primary care physicians . The intervention consisted of physician reminders , treatment guidelines endorsed by local opinion leaders , and patient education . Our primary objective was to examine whether this intervention improved the diagnosis and treatment of osteoporosis in this high-risk population . Secondary objectives included examining the effect of this intervention on patients ' knowledge , satisfaction , and quality of life . Methods Setting and Participants Capital Health ( Edmonton , Alberta ) is one of the largest integrated health service delivery organizations in Canada ( 20 ) . It provides comprehensive health services for about 1 million people and has an annual budget of almost $ 2 billion ( Canadian ) ( 20 ) . Primary care is delivered by approximately 900 fee-for-service physicians . We enrolled participants from the 2 largest emergency departments in the region : the University of Alberta Hospital ( a university-based teaching hospital ) and the Royal Alex and ra Hospital ( a university-affiliated community teaching hospital ) . These emergency departments provide most of the fracture care and emergency orthopedic services to the region . Consecutive patients presenting to the emergency department with a wrist fracture were potentially eligible . Inclusion criteria were as follows : age 50 years or older ; any simple , closed fracture of the distal forearm ; and discharge home . We excluded patients who were already taking prescription treatments for osteoporosis . Because we did not ask patients whether they had a diagnosis of osteoporosis until study closeout , a patient with a history of osteoporosis who was not being treated with prescription medication was potentially eligible for inclusion . We also excluded patients who were unable to provide consent , were unwilling to participate , were admitted to the hospital , resided in a long-term care facility , resided outside the Capital Health region , or could not read and converse in English . Study Design and Patient Enrollment We conducted a prospect i ve controlled trial with blinded ascertainment of outcomes . To allocate patients to the intervention or usual care control groups , we adapted and modified an onoff 1-site study design for 2 sites ( 21 ) . For 1 month at a time , in sequential order , the intervention was on at 1 emergency department while it was off at the other . At the end of each month , research nurses alternated intervention status from on to off or vice versa . Patients with wrist fractures were treated , as appropriate , by emergency department physicians and then approached by research nurses or orthopedic technicians for enrollment in the study before discharge home . We obtained informed consent from each patient , and all data were maintained outside the emergency departments in a central ized secure file system . The University of Alberta Health Research Ethics Board approved the study . Intervention We design ed an intervention to overcome the many barriers that exist for primary care physicians who are trying to adopt evidence -based treatments for their patients with osteoporosis . Each of the 3 components of the intervention had published evidence of effectiveness ( 22 - 24 ) . Physician Reminders A reminder was generated for each patient and faxed to the primary care physician of record . The reminder notified physicians that their patient had recently been seen and treated in the emergency department for a wrist fracture and reminded them that their patient was now considered to be at increased risk for osteoporosis . Generating and sending the personalized and patient-specific reminder took about 6 minutes for each patient . Treatment Guidelines Generated and Endorsed by Opinion Leaders As part of the reminder , we provided brief evidence -based treatment recommendations . These guidelines were design ed to fit on the same page and emphasized 3 points : 1 ) The patient is at very high risk for osteoporosis and needs a bone mineral density measurement if one has not been performed in the past year ; 2 ) without treatment , the patient may be at increased risk for another fracture within the year ; and 3 ) bisphosphonate treatment will reduce the patient 's risk for fracture by about 50 % . Bisphosphonate alternatives ( for example , calcitonin , raloxifene , and hormone therapy ) were mentioned as second-line approved treatments because , at the time of study design , only the bisphosphonates had been demonstrated to prevent both vertebral and nonvertebral fractures . Using previously vali date d methods ( 25 , 26 ) , we recruited 5 osteoporosis opinion leaders who had been nominated by local primary care providers . The opinion leaders helped develop and then endorsed the guidelines by attaching their names and signatures . Patient Education We provided patients in the intervention group with a tailored , single-page summary of osteoporosis information that mirrored the physician material s described in the preceding paragraph . We reinforced these written material s with a brief telephone counseling session that took place within 1 week of the fracture . This counseling ( approximately 4 minutes per session ) reiterated the content of the written material s and encouraged patients to seek further information and counseling from their primary care physician . We did not provide intervention patients with any written material s or counseling regarding fall prevention or home safety . Control Patients ( Usual Care ) On the basis of surveys and in-depth interviews with emergency department physicians in Canada and the United States , the current st and ard of care for patients treated for a wrist fracture usually consists of 1 ) notification to the primary care physician of record that the patient was seen and treated and 2 ) information on follow-up plans . We ensured that such notifications occurred for all control patients . In addition , we enhanced usual care by ensuring that control patients received educational material s and telephone counseling regarding fall prevention and home safety . During the call , patients were encouraged to visit their primary care physician for more detailed advice and a medication review . They did not receive any counseling or educational material s about osteoporosis . Thus , control patients received the same amount of attention and care as the intervention patients . After the main study was completed , all control patients were crossed over to the osteoporosis intervention , and all intervention patients were provided with counseling regarding fall prevention and home safety . Outcomes and Measurements The primary study outcome was", "BACKGROUND Treatment of osteoporosis following a hip fracture has been notoriously poor . Many efforts have been made to improve treatment rates . The purpose of this study was to determine whether a perioperative inpatient intervention program , involving patient education and providing a list of questions for the primary care physician , increased the percentage of patients in whom osteoporosis was addressed following a hip fracture . METHODS A prospect i ve , r and omized trial involving eighty patients who had been admitted to an academic medical center with a low-energy hip fracture was conducted . During their hospitalization , the study group patients were engaged in a fifteen-minute discussion regarding the association between osteoporosis and hip fractures , the efficacy of dual-energy x-ray absorptiometry scans in the diagnosis of osteoporosis and of bisphosphonates in its treatment , and the importance of medical follow-up for osteoporosis management . These patients were also provided with five questions regarding osteoporosis treatment to be given to their primary medical physician , and they were reminded about the questions during a follow-up telephone call six weeks later . The patients in the control group received a brochure describing methods for preventing falls . Both groups were contacted by telephone at six months after discharge to determine whether osteoporosis had been addressed . Positive indicators of intervention included assessment of bone mineral density with dual-energy x-ray absorptiometry and initiation of antiresorptive therapy . RESULTS The average age in each group was eighty-two years , and 78 % of the patients were female . Four patients in each group did not survive through the six-month follow-up period and were excluded from the trial . Fifteen ( 42 % ) of the thirty-six patients who had been r and omized to the study group , compared with only seven ( 19 % ) of the thirty-six patients in the control group , had their osteoporosis addressed by their primary physician . This difference between the groups was significant ( p = 0.036 ) . CONCLUSIONS Patients who were provided with information and questions for their primary care physician about osteoporosis were more likely to receive appropriate therapeutic intervention than were patients who had not received the information and questions . Orthopaedic surgeons have a unique opportunity to improve the rate of osteoporosis treatment in the perioperative period following a hip fracture by educating patients and directing them toward channels for long-term osteoporosis management", "Background : Older patients who experience a fragility fracture are at high risk of future fractures but are rarely tested or treated for osteoporosis . We developed a multifaceted intervention directed at older patients with wrist fractures ( in the form of telephone-based education ) and their physicians ( in the form of guidelines endorsed by opinion leaders , supported by reminders ) to improve the quality of osteoporosis care . Methods : In a r and omized controlled trial with blinded ascertainment of outcomes , we compared our intervention with usual care ( provision of printed educational material s to patients ) . Eligible patients were those older than 50 years of age who had experienced a wrist fracture and were seen in emergency departments and fracture clinics ; we excluded those who were already being treated for osteoporosis . The primary outcome was bisphosphonate treatment within 6 months after the fracture . Secondary outcomes included bone mineral density testing , “ appropriate care ” ( consisting of bone mineral density testing with treatment if bone mass was low ) and quality of life . Results : We screened 795 patients for eligibility and r and omly assigned 272 to the intervention ( 137 patients ) or control ( 135 patients ) group . The median age was 60 years ; 210 ( 77 % ) of the subjects were women , and 130 ( 48 % ) reported a previous fracture as an adult . Six months after the fracture , 30 ( 22 % ) of the intervention patients , as compared with 10 ( 7 % ) of the control patients , were receiving bisphosphonate therapy for osteoporosis ( adjusted relative risk [ RR ] 2.6 , 95 % confidence interval [ CI ] 1.3–5.1 , p = 0.008 ) . Intervention patients were more likely than control patients to undergo bone mineral density testing ( 71/137 [ 52 % ] v. 24/135 [ 18 % ] ; adjusted RR 2.8 , 95 % CI 1.9–4.2 , p receive appropriate care ( 52/137 [ 38 % ] v. 15/135 [ 11 % ] ; adjusted RR 3.1 , 95 % CI 1.8–5.3 , p died , and 4 others experienced recurrent fracture . Interpretation : A multifaceted intervention directed at high-risk patients and their physicians substantially increased rates of testing and treatment for osteoporosis . Nevertheless , more than half of the patients in the intervention group were not receiving appropriate care 6 months after their fracture , which suggests that additional strategies should be explored . ( Clinical Trials.gov trial register no. NCT00152321 .", "BACKGROUND Patients who survive hip fracture are at high risk of recurrent fractures , but rates of osteoporosis treatment 1 year after sustaining a fracture are less than 10 % to 20 % . We have developed an osteoporosis case manager intervention . The case manager educated patients , arranged bone mineral density tests , provided prescriptions , and communicated with primary care physicians . The intervention was compared with usual care in a r and omized controlled trial . METHODS We recruited from all hospitals that participate in the Capital Health system ( Alberta , Canada ) , including patients 50 years or older who had sustained a hip fracture and excluding those who were receiving osteoporosis treatment or who lived in a long-term care facility . Primary outcome was bisphosphonate therapy 6 months after fracture ; secondary outcomes included bone mineral density testing , appropriate care ( bone mineral density testing and treatment if bone mass was low ) , and intervention costs . RESULTS We screened 2219 patients and allocated 220 , as follows : 110 to the intervention group and 110 to the control group . Median age was 74 years , 60 % were women , and 37 % reported having had previous fractures . Six months after hip fracture , 56 patients in the intervention group ( 51 % ) were receiving bisphosphonate therapy compared with 24 patients in the control group ( 22 % ) ( adjusted odds ratio , 4.7 ; 95 % confidence interval , 2.4 - 8.9 ; P Bone mineral density tests were performed in 88 patients in the intervention group ( 80 % ) vs 32 patients in the control group ( 29 % ) ( P bone mineral density testing , 25 ( 21 % ) had normal bone mass . Patients in the intervention group were more likely to receive appropriate care than were patients in the control group ( 67 % vs 26 % ; P intervention cost was $ 50.00 per patient . CONCLUSION For a modest cost , a case manager was able to substantially increase rates of osteoporosis treatment in a vulnerable elderly population at high risk of future fractures", "Recognizing Osteoporosis and its Consequences in Quebec ( ROCQ ) is an ongoing patient health-management programme aim ed at evaluating the diagnostic and treatment care gaps for osteoporosis following a fragility fracture , and subsequently initiating and measuring interventions to decrease these gaps in women 50 years of age and over . Hospitals servicing approximately half of the population of the Province of Quebec ( Canada ) are participating in the ROCQ programme . Women with fragility and traumatic fractures are approached during their visit to a cast or outpatient clinic and are subsequently contacted by telephone 0 to 16 weeks after their fracture ( phase 1 ) . During the first phone contact , they are invited to answer a question naire aim ed at identifying the specific circumstances of their fracture and asked to participate in an observational study that could last up to 18 months . Based on this initial question naire , patients are classified as having either experienced a fragility or traumatic fracture . During the first phone contact , there is no reference about the possible association between the fracture and osteoporosis and no investigation or intervention is proposed . Six to eight months after the fracture event ( phase 2 ) , women are again contacted by phone to complete a question naire that evaluates the diagnostic and treatment rates for osteoporosis . At this phase of the programme , women with fragility fractures are r and omized to one of the three following intervention groups : 1 ) Educational Video Group , 2 ) Documentation Group and 3 ) Control Group . Participants are contacted 12 to 14 months after the intervention ( phase 3 ) to evaluate the efficacy of the interventions on the diagnosis and treatment rates of osteoporosis . All participants with fragility or traumatic fractures who consent will be followed for 20 years using data from the Québec Ministry of Health data base to measure the association between the index fracture and future fracture risk", "This article reports a controlled trial to investigate the effectiveness of patient education and a physician alerting system in altering secondary osteoporosis prevention after a low-trauma ( fragility ) wrist fracture and to record the current rate of osteoporosis investigation following such fractures . Fifty-one women and men aged 50 years or older with a low-trauma wrist fracture were identified ( 41 women and 10 men ; mean age [ 95 % CI ] , 71.51 [ 67.31 - 74.81 ] ) . The intervention group received a four-part intervention aim ed at both the patient and the family physician in addition to the usual care for the fracture . The control group only received usual care for the fracture . Data were collected for both groups at six weeks and six months . Results indicate that 92 % of the intervention subjects were investigated for osteoporosis , compared with the usual-care group , in which only 23 % were investigated . Early osteoporosis intervention has the potential to limit disease impact , and h and therapists can play a key role in early identification of osteoporosis", "OBJECTIVE We previously demonstrated that a case manager intervention improved osteoporosis ( OP ) treatment within 6 months of hip fracture compared with usual care . The second phase of the r and omized trial compared a less intensive intervention , facilitated bone mineral density ( BMD ) testing , with usual care and the case manager intervention . METHODS We initially r and omized 220 hip fracture patients to either an OP case manager intervention or usual care . After completing the original trial at 6 months postfracture , usual care patients were reallocated to facilitated BMD testing ; BMD tests were arranged and results sent to primary care physicians . Main outcomes ( bisphosphonate treatment , BMD tests , receipt of appropriate care ) were reascertained 1 year following hip fracture and compared with outcomes achieved by the OP case manager intervention and usual care . RESULTS Compared with usual care , facilitated BMD testing increased testing from 29 % to 68 % ( P bisphosphonate use from 22 % to 38 % ( P of appropriate care from 26 % to 45 % ( P OP case manager intervention led to significantly higher bisphosphonate use ( 54 % versus 38 % ; P = 0.03 ) , receipt of appropriate care ( 71 % versus 45 % ; P BMD testing ( 80 % versus 68 % ; P = 0.06 ) than usual care followed by facilitated BMD testing . CONCLUSION Compared with usual care , 2 different inexpensive interventions result ed in significant increases in appropriate management of OP after hip fracture . The magnitude of improvements achieved was directly related to the intensity of the interventions" ]	4118994c-06ff-11f0-808a-c43d1ab1c353
OBJECTIVE To use a systematic review to determine which material s and technique/ protocol present the highest success rate in bonding brackets to porcelain surfaces . MATERIAL S AND METHODS Different data bases were search ed without limitations up to July 2013 . Additionally , the bibliographies of the finally selected articles were h and search ed to identify any relevant publications that were not identified earlier . In vitro and in vivo articles were included . RESULTS No in vivo articles were found that fulfilled the inclusion criteria . A total of 45 in vitro articles met all inclusion criteria . They were published between 2000 to July 2013 . CONCLUSIONS The best protocol described in this review is the etching of 9.6 % hydrofluoric acid for 1 minute , rinsed for 30 seconds , and then air-dried . The etching of hydrofluoric acid should be followed by an application of silane . Considering the harmful effects of etching with hydrofluoric acid , another appropriate suggestion is mechanical roughening with s and blasting followed by an application of silane	[ "The aim of this study was to determine the optimum silane-coupling agent and the optimum concentration of acid agent when bonding to porcelain surfaces . Eighty deglazed feldspathic porcelain discs with a diameter of 10 mm and a thickness of 2 mm mounted in acrylic resin blocks were r and omly divided into four groups . In groups 1 and 2 , the porcelain surfaces were etched with 9.6 per cent hydrofluoric ( HF ) acid and in groups 3 and 4 with 5 per cent HF acid . In groups 1 and 3 , the Dynalock maxillary central incisor brackets were bonded with Pulpdent silane and Unite bonding adhesive and in groups 2 and 4 with Reliance silane and Unite . Shear forces were applied to the sample s using an Instron universal test machine . The non-parametric Kruskal-Wallis test was used to determine significant differences in bond strengths between the four groups and Dunn 's multiple comparison test to compare subgroups . The mean bond strengths and st and ard deviations of groups 1 to 4 were 5.51 + /- 1.19 , 6.54 + /- 0.002 , 4.55 + /- 1.93 , and 6.39 + /- 0.45 MPa , respectively . Specimens bonded with Reliance showed a statistically significantly higher in vitro bond strength than those bonded with Pulpdent . The concentration of etching gels did not result in any statistically significant difference on the in vitro bond strength when evaluated separately", "The objectives of this study were to test the efficiency of LED curing devices in bonding ceramic brackets to porcelain surfaces and to compare the effects of LED and halogen curing techniques on shear bond strength of ceramic brackets . A total of 20 glazed porcelain facets were r and omly divided into two groups of 10 . Porcelain surfaces were etched with 9.6 % hydrofluoric acid for 2 minutes , and silane was applied on the etched porcelain surface . Ceramic brackets were bonded with an LC composite resin cured with soft start mode LED and a halogen light . Bond strengths , as determined in the shear mode , were higher in the LED group ( P LED curing units with the soft start polymerization mode were more effective than halogen curing units in bonding ceramic brackets on porcelain surfaces . The type of curing light must be considered as an important factor affecting bond strength of ceramic brackets on porcelain surfaces", "OBJECTIVE To test the None hypothesis that surface treatment has no influence on the micro-shear bond strength between orthodontic composite resin cement and ceramics ( feldspathic porcelain ) . MATERIAL S AND METHODS Circular specimens of feldspathic porcelain were fabricated and r and omly divided into six groups : ( 1 ) no treatment ; ( 2 ) treatment with a mixture of acidic primer and silane agent for 20 seconds ; ( 3 ) etching with 9.5 % hydrofluoric acid ; ( 4 ) etching with 9.5 % hydrofluoric acid and coating with a mixture of acidic primer and silane agent for 20 seconds ; ( 5 ) airborne-particle abrasion with 50-mum aluminum oxide ; and ( 6 ) airborne-particle abrasion and coating with a mixture of acidic primer and silane agent for 20 seconds . The porcelain disks were then bonded to resin cylinders with composite resin cement . A micro-shear bond test was carried out to measure the bond strength . Moreover , each ceramic surface was observed morphologically by scanning electron microscopy . One-way analysis of covariance was used to compare the groups for differences in micro-shear bond strength . RESULTS The mean micro-shear bond strength varied as a function of surface treatment . It ranged from 3.7 to 20.8 MPa . The highest values for micro-shear bond strength were found when the surface was acid-etched with hydrofluoric acid and coated with silane . On the other h and , the control group ( no treatment ) had significantly lower micro-shear bond strength than all the other groups . CONCLUSION The None hypothesis that the surface treatment has no influence on the micro-shear bond strength of orthodontic composite resin was rejected . The bond strength between ceramics and orthodontic resin cement is affected by the ceramic surface treatment . The bond failure was of the adhesive type , except with the hydrofluoric acid + silane group , where it was a cohesive bond failure", "The aim of this research was to verify , in vitro , the effect of various porcelain surface treatment on the shear strength of orthodontic brackets bonded to porcelain and the mode of fracture after debonding . Eighty-eight sample s of metallic supported feldspathic porcelain were r and omly divided into four groups according to their surface preparation as follows : the porcelain was maintained intact ( GI ) , roughened with a diamond bur ( GII ) , etched with 10 % hydrofluoric acid ( GIII ) , or s and blasted with aluminum oxide ( GIV ) . The specimens were treated with silane ( Scotchprime ) and brackets were bonded with Concise . Each sample was subjected to a shear load at a crosshead speed of 1 mm/min and a recording was made at the point of failure . Bond strengths , adequate to withst and the application of orthodontic forces , were achieved in all groups . The Kruskal-Wallis statistical test showed no significant differences in bond strength between the groups ( p > 0.05 ) . However , many more porcelain fractures occurred on deglazed porcelain . This study indicates that with the appropriate material selection , the silane/composite procedure alone may be adequate for bonding", "This in vitro study investigated the influence of using different combinations of bracket , adhesive , and light-curing source on the tensile bond strength to porcelain and on failure patterns at debonding . Tensile tests were performed using : one ceramic bracket versus one metal bracket , two orthodontic composites ; type bisphenol A-glycidyldimethacrylate and urethane dimethacrylate ( UDMA ) , and four light-curing units with the same range of emission spectrum but various light intensities : three light-emitting diode ( LED ) units and one halogen-based unit . One hundred and sixty porcelain sample s were r and omly divided into 16 equal groups . The porcelain surface was conditioned with 9 per cent hydrofluoric acid before silane application . The composite was photo-polymerized for 40 seconds . After storage in water at 37 ° C for 24 hours , the sample s were subjected to tensile force until bond failure . Bond strength and bond failure mode were recorded ; results were analysed ( α = 0.05 ) using R language ; linear model with constant variance for the bond strength and multinomial distribution for the failure mode . The bond strength in all groups was sufficient to withst and orthodontic treatment ( > 6 MPa ) . There was no statistical difference between the adhesives , but comparing bracket × light interaction , it was significantly higher with the ceramic bracket . No significant differences were seen between the metal bracket groups , but for the ceramic bracket , the results were significantly higher with the LED light . No fracture was observed in porcelain with the metal bracket but it occurred in 35 per cent of the ceramic bracket sample s and the risk was higher when using UDMA composite and lower with LED high intensity light ", "The purpose of this study was to evaluate the effects of a new self-etching primer/ adhesive used to enhance the shear strength of orthodontic brackets bonded to porcelain surfaces . Forty-five porcelain maxillary central incisor teeth were used in the study . The teeth were divided r and omly into three groups : group I ( control ) , the porcelain teeth were etched with 37 % phosphoric acid followed by a sealant and the brackets were bonded with a composite adhesive ; group II , the porcelain teeth were microetched and hydrofluoric acid and silane applied and metal brackets were then bonded with the composite adhesive ; and group III , the porcelain teeth were etched with phosphoric acid and a self-etching primer/adhesive applied before bonding . Brackets precoated with the adhesive were used on all three groups of teeth . All teeth were stored for 24 hours at 37 degrees C before debonding . The results of the analysis of variance ( F = 10.7 ) indicated that there was a significant difference ( P = .001 ) between the three groups . The mean shear bond strengths of conventional bonding using a 37 % phosphoric acid and sealant was 4.4 + /- 2.7 MPa , whereas that of microetching followed by the application of hydrofluoric acid and silane was 11.2 + /- 4.7 MPa , and for the new self-etching primer/adhesive it was 10.3 + /- 5.3 MPa . The last two groups had the highest bond strength values and were not significantly different from each other", "The aim of this study was to compare the effects of various porcelain surface-conditioning techniques , used either alone or in combination , on the shear bond strength ( SBS ) of ceramic brackets cured with a light emitting diode ( LED ) . Thirty glazed porcelain facets were r and omly divided into three groups of 10 . In group I , the porcelain surfaces were etched with 9.6 per cent hydrofluoric acid ( HFA ) for 2 minutes before silane application , in group II , the porcelain surfaces were s and blasted with aluminium oxide particles , etched with 9.6 per cent HFA for 2 minutes , and silane applied , and in group III , the porcelain surfaces were s and blasted with aluminium oxide particles before silane application . Spirit ceramic brackets were bonded with a light-cured composite resin ( Light Bond ) and a LED . All specimens were stored in distilled water at 37 degrees C for 24 hours and thermocycled . Bond strength was determined in shear mode at a crosshead speed of 0.5 mm/minute until fracture occurred . Analysis of variance indicated a significant difference between groups ( P lowest SBS was found in group III ( 5.46 + /- 1.34 , P 0.05 ) . Surface treatment with HFA and a silane coupling agent produced the highest bond strength . S and blasting before HFA and silane application did not significantly increase bond strength . Silane application to s and blasted porcelain provided poor results in vitro and clinical trials are needed to determine its reliability for bonding ceramic brackets to ceramic crowns", "In this study , shear bond strength ( SBS ) of metal orthodontic brackets to porcelain following conditioning by Er : YAG ( erbium-doped yttrium aluminum garnet ) and Nd : YAG ( neodymium-doped yttrium aluminum garnet ) laser in comparison to conventional methods was evaluated . One hundred glazed porcelain discs with an upper central shape were prepared and r and omly assigned to five equal groups of 20 . In the first group , sample s were only deglazed and roughened by diamond burs . In the second group , after roughening and deglazing of porcelain sample s , the sample s were etched by 9.6 % hydrofluoric acid for 4 min . Groups , 3 , 4 , and 5 were prepared by 0.8-W Nd : YAG laser , 2-W Er : YAG laser , 3-W Er : YAG laser for 10 s , respectively . Then , metal , mesh-based brackets were bonded to porcelain sample s , and after being stored in distilled water for 24 h , debonding was carried out by a Zwick testing machine . ANOVA and Tukey tests were used to compare SBS in five groups . Mean SBS in groups 1 to 5 were 3.3 ± 1.6 , 7.0 ± 2.1 , 6.9 ± 2.7 , 2.3 ± 1.1 , and 3.7 ± 2.3 MPa , respectively . ANOVA test revealed a significant difference between five groups ( p Tukey ’s test showed SBS in groups 2 and 3 were significantly higher than the other groups , they did not differ with each other significantly ( p > 0.05 ) . The results revealed that SBS of 9.6 % hydroflouric acid and Nd : YAG Laser was in an acceptable range for orthodontic treatment . Nd : YAG laser was shown to be an acceptable substitute for hydrofluoric acid while Er : YAG laser with the mentioned power and duration was not a suitable option", "This study evaluated the effects of 5 different surface conditioning methods on the bond strength of polycarbonate brackets bonded to ceramic surfaces with resin based cement . Six disc-shaped ceramic specimens ( feldspathic porcelain ) with glazed surfaces were used for each group . The specimens were r and omly assigned to 1 of the following treatment conditions of the ceramic surface : ( 1 ) orthophosphoric acid + primer + bonding agent , ( 2 ) hydrofluoric acid gel + primer + bonding agent , ( 3 ) tribochemical silica coating ( silicon dioxide , 30microm ) + silane , ( 4 ) airborne particle abrasion ( aluminum trioxide , 30microm ) + silane , and ( 5 ) airborne particle abrasion ( aluminum trioxide , 30microm ) + silane + bonding agent . Brackets were bonded to the conditioned ceramic specimens with a light-polymerized resin composite . All specimens were stored in water for 1 week at 37 degrees C and then thermocycled ( 1000 cycles , 5 degrees C to 55 degrees C , 30 seconds ) . The shear bond strength values were measured on a universal testing machine at a crosshead speed of 1 mm/min . Brackets treated with silica coating with silanization had significantly greater bond strength values ( 13.6 MPa , P = .01 ) than brackets treated with orthophosphoric acid ( 8.5 MPa ) . There was no significant difference ( P = .97 ) between the bond strengths obtained after airborne abrasion with aluminium trioxide particles followed by silanization ( 12 MPa ) and hydrofluoric acid application ( 11.2 MPa ) ( ANOVA and Tukey test ) . Although brackets conditioned with orthophosphoric acid exhibited only adhesive failures of the luting cement from the ceramic surface , other conditioning methods showed mixed types of failures . Airborne particle abrasion with aluminium trioxide or silica coating followed by silanization gave the most favorable bond strengths . The types of failures observed after debonding indicated that the critical parameter was the strength of the adhesive joint of the luting cement to both the bracket and the ceramic", "The purpose of this study was to compare the effects of time on the shear bond strength of a resin-reinforced glass ionomer and a composite adhesive system specifically ( 1 ) within half an hour after bonding the bracket to the tooth and ( 2 ) at least 24 hours from the time of bonding when the adhesive has achieved most of its bond strength . Ninety-one freshly extracted human molars were collected and stored in a solution of 0.1 % ( weight/volume ) thymol . The teeth were cleaned and polished . The teeth were r and omly separated into four groups : Group I , glass ionomer adhesive debonded within 30 minutes from initial bonding ; Group II , glass ionomer adhesive debonded after 24 hours immersion in deionized water at 37 degrees C ; Group III , composite adhesive debonded within 30 minutes from initial bonding ; Group IV , composite adhesive debonded after 24 hours immersion in deionized water at 37 degrees C. The results of the analysis of variance comparing the 4 experimental groups ( F = 59 . 3 ) indicated the presence of significant differences between the 4 groups ( P = .0001 ) . In general , the shear bond strengths were significantly greater in the 2 groups debonded after 24 hours . This was true for both the resin-modified glass ionomer ( x = 8.8 + /- 3.6 MPa ) and the composite ( x = 10.4 + /- 2.8 MPa ) adhesives . On the other h and , the shear bond strengths were significantly lower in the 2 groups debonded within 30 minutes of their initial bonding . The bond strength of the resin-modified glass ionomer adhesive ( x = 0.4 + /- 1.0 MPa ) was significantly lower than that for the composite ( x = 5.2 + /- 2.9 MPa ) adhesive . The present findings indicated that the resin reinforced glass ionomer adhesive has a significantly lower initial bond strength but increased more than 20-fold within 24 hours . In comparison , the composite adhesive has a significantly larger initial bond strength that doubled within 24 hours . The clinician needs to take these properties into consideration when ligating the initial arch wires", "The purpose of this study was to compare the bond strengths of three different adhesive systems when used alone and combined with a porcelain priming agent to bond ceramic brackets to porcelain surfaces . Sixty porcelain specimens were r and omly assigned to the six different treatment groups . Half were bonded with the porcelain priming agent and one of the adhesive systems and the other half with one of the adhesive systems alone . The shear bond strengths of all specimens were tested , with an Instron testing machine , 10 minutes after being bonded . The surface of the porcelain and the bracket base were examined , with scanning electron microscopy ( SEM ) and qualitative energy dispersive x-ray analysis ( EDS ) , to determine the bond failure patterns and to check the porcelain surface for the presence of cracks and fractures . There was a statistically significant difference within each adhesive between those sample s with the priming agent and those without the priming agent . Differences between the three adhesives were not statistically significant ( p≤0.05 )", "OBJECTIVE Verify the in vitro effectiveness of different porcelain surface polishing systems used after orthodontic debonding . MATERIAL S AND METHODS Restorations were simulated by 52 metallic sample s covered with glazed feldspathic porcelain . Four of these intact sample s composed the control group ( C ) . The remaining sample s were divided into four groups ( n = 12 ) , according to the surface preparation they were to receive : no surface treatment ( G1 ) ; roughened with a diamond bur ( G2 ) ; etched with 10 % hydrofluoric acid ( G3 ) ; and s and blasted with aluminum oxide ( G4 ) . All experimental sample s were treated with silane and bonded with a primer and st and ardized amount of adhesive . After composite removal , each group was divided into subgroups r and omly ( n = 4 ) , according to the porcelain polishing system used : Edenta ( P1 ) ; Identoflex ( P2 ) ; and Komet ( P3 ) . All 52 sample -surfaces were evaluated quantitatively with a profilometer , and a mean roughness profile ( Ra ) value was determined for each sample . Both control and experimental specimens were evaluated qualitatively using a scanning electron microscope ( SEM ) to assess surface morphology . RESULTS Statistical analysis with analysis of variance ( ANOVA ) and post-hoc Tukey multiple comparisons test showed statistical differences between surface preparation groups ( G1 not equal G2 = G3 = G4 ) , at alpha = .05 level of significance ; as for polishing protocol s , no statistical difference was found . CONCLUSIONS The surface preparation was the determinant for final surface texture . No combination between surface preparation and polishing system was able to reestablish the original glazed porcelain smoothness" ]	41189988-06ff-11f0-808a-c43d1ab1c353
Background and Objective Exercise is a widely accepted treatment known to improve walking ability in persons with peripheral arterial disease ( PAD ) ; however , it has not been confirmed as to whether exercise improves fitness and performance-based function and , consequently , performance of activities of daily living ( ADL ) . This systematic review aims to identify whether any mode of structured exercise improves physical fitness or performance-based tests of function and whether improvement in walking ability is related to an improvement in these outcomes . Data Sources and Study Selection Eligible studies included r and omized controlled trials ( RCTs ) using an exercise intervention for the treatment of intermittent claudication with fitness ( including the 6-min walk ( 6MW ) , aerobic capacity , shuttle and muscle strength ) tests and performance-based tests of function as the outcomes . Study Appraisal and Methods Assessment of study quality was performed using a modified version of the Physiotherapy Evidence Data base Scale ( PEDro ) . Relative effect sizes , mean differences ( MDs ) and 95 % confidence intervals were calculated and adjusted via Hedges ’ bias-corrected for small sample sizes . Regression analyses were performed to establish relationships between walking ability and fitness outcomes . Results Twenty-four RCTs met the inclusion criteria : 19 aerobic training interventions and 5 progressive resistance training ( PRT ) . In total 924 participants ( 71 % male ) were studied ; with few participants over 75 years of age and the mean ankle brachial index was mean ± st and ard deviation ( SD ) 0.66 ± 0.06 . The most common outcome measured was aerobic capacity ( 52 % of trials ) , which improved by 8.3 % ± 8.7 % on average . Although there were no significant relationships , up to 16 % of the variance in walking distances can be explained by changes in walking economy . Muscle strength was measured in only five trials , improving by 42 % ± 74 % on average . There was a strong significant relationship between change in plantar flexor muscle strength and change in initial claudication time ( r = 0.99 ; p = 0.001 ) and absolute claudication time ( r = 0.75 ; p = 0.05 ) measured on a treadmill across trials measuring this muscle group . The 6MW distance was measured in only 14 % of trials . Walking and PRT significantly improved 6MW initial claudication distance ( MD range 52–129 m ) and total walking distance ( MD range 36–108 m ) in studies that measured this outcome . Only one trial assessed performance-based tests of function , and they did not improve significantly . Conclusion Although data are limited , there is a strong significant relationship between plantar flexor muscle strength and treadmill walking ability . More research is needed to assess improvements in walking economy at specific timepoints and whether this translates to improvements in claudication outcomes and measurements pertaining to muscle strength . Future trials should focus on interventions that improve lower limb muscle strength and assess muscle strength , power and endurance across a variety of lower extremity muscle groups in order to underst and these relationships further . The 6MW , muscle strength and performance-based tests of function such as chair st and , balance scale , stair climb and gait speed are understudied in PAD . Future trials should examine the effects of exercise on performance-based tests of function , which may predict actual ADL performance and incident disability	[ "This study examined whether a training intervention likely to elicit adaptations in the leg could result in reduced leg pain and increased whole body physical capacity . Twenty-seven peripheral arterial disease ( PAD ) patients were r and omized to either an individual leg plantar flexion training group ( TG ) training 4 × 4 min intervals at 80 % of maximal work rate three times per week for 8 weeks or a control group . The TG significantly increased plantar flexion peak oxygen uptake and power output by 23.5 and 43.9 % , respectively . Treadmill peak oxygen uptake ( VO2peak ) significantly increased 12.3 % in the TG and was associated with a significant increased time to exhaustion of 20.0 % when treadmill walking . Eleven of 14 patients no longer reported leg pain limitations at VO2peak . No differences in cardiac output measured at VO2peak , or walking economy were observed . Plantar flexion training was effective in increasing VO2peak and walking performance , and may be a useful strategy in treatment of PAD", "1 . The activities of phosphofructokinase ( PFK ) , citrate synthetase ( CS ) , lactate dehydrogenase ( LDH ) , 3-hydroxyacyl-CoA dehydrogenase ( ACDH ) and cytochrome-c oxidase(Cyt-ox ) in the calf muscle tissue were compared in subjects with intermittent claudication ( n = 38 ) and controls ( n = 20 ) . The activities of CS , ACDH and Cyt-ox were increased and the activity of Cytox was positively correlated to the maximal walking distance ( MWD ) in the patients . 2 . Thirty-three patients with intermittent claudication were r and omized to three treatment groups : ( 1 ) operative surgery , ( 2 ) operative surgery supplemented with physical training and ( 3 ) physical training alone . Before and after 6 - 12 months of treatment , symptom-free walking distance ( SFWD ) , MWD , ankle-brachial blood pressure quotient ( ankle index ) , maximal plethysmographic calf blood flow ( MPBF ) and the activities of PFK , CS , LDH , ACDH and Cyt-ox were measured . 3 . SFWD and MWD increased in all three groups . Ankle index and MPBF increased in groups 1 and 2 , but were unchanged in group 3 . The activities of Cyt-ox and CS decreased with operation , but the activity of Cyt-ox was further augmented with training in group 3 . Overall , the change in ankle index explained 80 - 90 % of the variability in walking performance . In a separate analysis , the increased activity of Cyt-ox in group 3 was positively correlated to , and explained 31 % of the variability in , the improvement in SFWD . 4 . These findings indicate that both physical activity and a reduced calf blood flow are necessary conditions for the enzymatic adaptation to take place . A causal relationship between metabolic adaptation in the muscle tissue and walking performance is suggested . ( ABSTRACT TRUNCATED AT 250 WORDS", "BACKGROUND In patients with intermittent claudication , a supervised walking exercise program increases peak exercise performance and community-based functional status . Patients with peripheral arterial disease also have muscle weakness in the affected extremity that may contribute to the walking impairment . However , the potential benefits of training modalities other than walking exercise , such as strength training , have not been critically evaluated in this patient population . The present study tested the hypothesis that a strength training program would be as effective as treadmill walking exercise and that combinations of strengthening and walking exercise would be more effective than either alone in improving exercise performance . METHODS AND RESULTS Twenty-nine patients with disabling claudication were r and omized to 12 weeks of supervised walking exercise on a treadmill ( 3 h/wk at a work intensity sufficient to produce claudication ) , strength training ( 3 h/wk of resistive training of five muscle groups of each leg ) , or a nonexercising control group . Grade d treadmill testing was performed to maximally tolerated claudication pain to define changes in peak exercise performance . After 12 weeks , patients in the treadmill training program had a 74 + /- 58 % increase in peak walking time as well as improvements in peak oxygen consumption ( VO2 ) and the onset of claudication pain . Patients in the strength-trained group had a 36 + /- 48 % increase in peak walking time but no change in peak VO2 or claudication onset time . Control subjects had no changes in any of these measures over the 12-week period . After the first 12 weeks , patients in the initial walking exercise group continued for 12 more weeks of supervised treadmill training . This result ed in an additional 49 + /- 53 % increase in peak walking time ( total of 128 + /- 99 % increase over the 24 weeks ) . After the initial 12 weeks , patients in the strength-trained group began 12 weeks of supervised treadmill training , and patients in the control group participated in a 12-week combined program of strengthening and treadmill walking exercise . The combined strength and treadmill training program and treadmill training after 12 weeks of strength training result ed in increases in peak exercise performance similar to those observed with 12 weeks of treadmill training alone . CONCLUSIONS A supervised treadmill walking exercise program is an effective means to improve exercise performance in patients with intermittent claudication , with continued improvement over 24 weeks of training . In contrast , 12 weeks of strength training was less effective than 12 weeks of supervised treadmill walking exercise . Finally , strength training , whether sequential or concomitant , did not augment the response to a walking exercise program", "Patients with atherosclerotic peripheral arterial disease ( PAD ) of the lower extremities have impaired walking ability due to exercise-induced muscle ischemia and the result ant pain of intermittent claudication . To evaluate the benefit of exercise training as a treatment for patients with PAD , as well as possible mechanisms associated with improvement , we r and omly assigned 19 men with disabling claudication to treated and control groups . Treatment consisted of supervised treadmill walking ( 1 hr/day , 3 days/wk , for 12 weeks ) with progressive increases in speed and grade as tolerated . Grade d treadmill testing was performed to maximal toleration of claudication pain on entry and after 12 weeks of training to define changes in peak exercise performance . After 12 weeks , treated subjects had increased their peak walking time 123 % , peak oxygen consumption 30 % , and pain-free walking time 165 % ( all p less than 0.05 ) . Control subjects had no change in peak oxygen consumption , but after 12 weeks , peak walking time increased 20 % ( p less than 0.05 ) . In treated subjects , maximal calf blood flow ( measured by a plethysmograph ) increased 38 + /- 45 % ( p less than 0.05 ) , but the change in flow was not correlated to the increase in peak walking time . Elevated plasma concentrations of acylcarnitines have been associated with the functional impairment of PAD and may reflect the metabolic state of ischemic skeletal muscle . In treated subjects , a 26 % decrease in resting plasma short-chain acylcarnitine concentration was correlated with improvement in peak walking time ( r = -0.78 , p less than 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS", "OBJECTIVE Exercise advice is the main treatment for symptom relief in the UK for patients with mild to moderate Intermittent Claudication ( IC ) . Would a weekly exercise and motivation class for 6 months offer adjuvant benefit over written and verbal exercise advice alone ? PATIENTS AND METHODS Fifty-nine patients attending a regional vascular centre for whom IC was the main factor affecting mobility were r and omised to either exercise advice alone ( n=30 ) or exercise advice with a once a week 45 min supervised exercise/motivation class ( n=29 ) . The mean age was 68 years . Baseline and 6-month assessment included a Quality of Life Question naire -- the Short-Form-36 , the Charing Cross Symptom Specific Claudication Question naire ( CCCQ ) and treadmill walking distance ( 3.5 km/h 12 % ) . RESULTS At 6-month follow-up the supervised exercise group had improved their treadmill walking by 129 % compared to 69 % in the advice alone group ( p=0.001 ) . This significant improvement was maintained at the subsequent 9 and 12-month follow-up assessment s. By the 9-month stage the advice only group CCCQ score had improved 16 % from baseline , while the supervised exercise group had a significantly better 43 % improvement in base line score ( p Self reported frequency of walks was higher in the exercise class group being significant for improvement in CCCQ score . CONCLUSION A weekly , supervised exercise and motivation class for a 6-month period provides a significant improvement in patients ' symptoms , quality of life , and distance walked compared with advice alone and this improvement continues after attendance at class has ceased", "OBJECTIVE The efficacy of polestriding exercise ( walking with modified ski poles with a movement pattern similar to cross-country skiing ) to increase exercise tolerance of persons with intermittent claudication pain caused by peripheral arterial disease was tested in this 24-week prospect i ve r and omized clinical trial . METHODS The study was conducted in a Department of Veterans Affairs Hospital with 52 individuals who gave written informed consent and were r and omized into either a polestriding exercise ( n = 27 ; age , 65.5 + /- 7.0 years ; ankle brachial index , 0.64 + /- 0.25 ) or nonexercise control ( n = 25 ; age , 68.6 + /- 8.9 years ; ankle brachial index , 0.69 + /- 0.14 ) group ( P > .05 for all comparisons ) . The polestriding exercise program consisted of supervised training three times per week for 4 weeks , two times per week for 8 weeks , one time per week for 4 weeks , biweekly for 4 weeks and unsupervised training for 4 weeks . Starting in week 5 , subjects took their poles home with instructions to repeat the most recent supervised training walk at an appropriate and convenient location near their residence . This was referred to as unsupervised but directed exercise . Subjects were provided with a personal log book for documenting unsupervised exercise sessions . With both supervised and unsupervised exercise , subjects were expected to complete a total of four 30-minute to 45-minute polestriding exercise sessions per week . The main outcome measures were exercise duration on symptom-limited incremental treadmill test , Walking Impairment Question naire , rating of perceived leg pain at baseline , 4 , 8 , 12 , 16 , and 24 weeks , and constant work-rate treadmill exercise tests at baseline and at 4 , 12 , and 24 weeks . RESULTS Polestriding significantly ( P exercise tolerance on the constant work-rate and incremental treadmill tests . Ratings of perceived claudication pain were significantly less after the polestriding training program . Subject perceived distance and walking speed scores on the Walking Impairment Question naire improved in the polestriding trained group only ( P polestriding training significantly improves quantitative and qualitative measures of the exercise tolerance of persons limited by intermittent claudication pain", "Supervised , hospital-based exercise rehabilitation programs are effective for improving functional status for patients with claudication due to peripheral arterial occlusive disease . However , it has been suggested that unsupervised , home-based exercise programs , which have been relatively little evaluated , would be equally efficacious as compared with hospital-based programs . The authors tested the hypothesis that a hospital-based exercise rehabilitation program would improve treadmill exercise perfor mance more than a home-based program . Of 20 consecutively enrolled patients with claudication , 10 were r and omly placed into a supervised , hospital-based program and 10 into an unsupervised , home-based program for a three-month period . Exercise perfor mance was evaluated by treadmill testing using a grade d protocol . In addition , func tional status was evaluated by the Walking Impairment Question naire ( WIQ ) and the Medical Outcomes Study SF-20 question naire ( MOS ) . Patients in the hospital-based program were treated with treadmill walking three times a week for one hour/visit . Patients in the home-based program were instructed to walk at least three times a week and were contacted weekly to provide encouragement and to record compliance with ( continued on next page ) the program . Patients in the hospital-based group improved peak walking time by 137 % , pain-free walking time by 150 % , and peak oxygen consumption by 19 % ( all P walking distance and speed according to WIQ data ( both P MOS physical functioning score in the hospital-based group improved by 20 percentage points ( P exercise performance measured on the treadmill . Improvement in the ability to walk on the treadmill was greater in the hospital-based than the home- based program ( P ability to walk distances was the only question naire measure that improved in persons who received the home-based program ( P improving treadmill exercise performance than an unsupervised , home-based program", "Background — This prospect i ve , r and omized , controlled clinical trial compared changes in exercise performance and daily ambulatory activity in peripheral artery disease patients with intermittent claudication after a home-based exercise program , a supervised exercise program , and usual-care control . Methods and Results — Of the 119 patients r and omized , 29 completed home-based exercise , 33 completed supervised exercise , and 30 completed usual-care control . Both exercise programs consisted of intermittent walking to nearly maximal claudication pain for 12 weeks . Patients wore a step activity monitor during each exercise session . Primary outcome measures included claudication onset time and peak walking time obtained from a treadmill exercise test ; secondary outcome measures included daily ambulatory cadences measured during a 7-day monitoring period . Adherence to home-based and supervised exercise was similar ( P=0.712 ) and exceeded 80 % . Both exercise programs increased claudication onset time ( P peak walking time ( P home-based exercise increased daily average cadence ( P0.05 ) . The changes in claudication onset time and peak walking time were similar between the 2 exercise groups ( P>0.05 ) , whereas the change in daily average cadence was greater with home-based exercise ( P home-based exercise program , quantified with a step activity monitor , has high adherence and is efficacious in improving claudication measures similar to a st and ard supervised exercise program . Furthermore , home-based exercise appears more efficacious in increasing daily ambulatory activity in the community setting than supervised exercise . Clinical Trial Registration — URL : http://www . Clinical Trials . Gov . Unique identifier : NCT00618670", "PURPOSE The effects of upper-limb ( arm cranking ) and lower-limb ( leg cranking ) exercise training on walking distances in patients with intermittent claudication was assessed . METHODS Sixty-seven patients ( 33 to 82 years old ) with moderate to severe intermittent claudication were recruited , and the maximum power generated during incremental upper- and lower-limb ergometry tests was determined , as were pain-free and maximum walking distances ( by using a shuttle walk test ) . Patients were r and omly assigned to an upper-limb training group ( n = 26 ) or a lower-limb training group ( n = 26 ) . An additional untrained group ( n = 15 ) was recruited on an ad hoc basis in parallel with the main trial by using identical inclusion criteria . This group was subsequently shown to possess a similar demographic distribution to the two exercise groups . Supervised training sessions were held twice weekly for 6 weeks . RESULTS Both training programs significantly improved the maximum power generated during the incremental upper- and lower-limb ergometry tests ( P central cardiovascular function that was independent of the training mode . More importantly , pain-free and maximum walking distances also improved in both training groups ( P upper-limb exercise training may result , in part , from systemic cardiovascular effects rather than localized metabolic or hemodynamic changes . CONCLUSION Carefully prescribed upper-limb exercise training can evoke a rapid symptomatic improvement in patients with claudication , while avoiding the physical discomfort experienced when performing lower-limb weight-bearing exercise", "The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , including a checklist and a flow diagram , was developed to help authors improve their reporting of r and omized controlled trials . Its primary focus was on individually r and omized trials with 2 parallel groups that assess the possible superiority of one treatment compared with another but is now being extended to other trial design s. Noninferiority and equivalence trials have method ological features that differ from superiority trials and present particular difficulties in design , conduct , analysis , and interpretation . Although the rationale for such trials occurs frequently , those design ed and described specifically as noninferiority or equivalence trials appear less commonly in the medical literature . The quality of reporting of those that are published is often inadequate . In this article , we present an adapted CONSORT checklist for reporting noninferiority and equivalence trials and provide illustrative examples and explanations for those items amended from the original CONSORT checklist . The intent is to improve reporting of noninferiority and equivalence trials , enabling readers to assess the validity of their results and conclusions", "PURPOSE To determine if improvements in physical function and peripheral circulation after 6 months of exercise rehabilitation could be sustained over a subsequent 12-month maintenance exercise program in older patients with intermittent claudication . METHODS Seventeen patients r and omized to exercise rehabilitation and 14 patients r and omized to usual care control completed this 18-month study . Patients exercised three times per week during the first 6 months of a progressive exercise program , followed by two times per week during the final 12 months of a maintenance program . Patients were studied at baseline , 6 months , and 18 months during the study . RESULTS Eighteen months of exercise rehabilitation increased the initial claudication distance by 373 meters ( 189 % ) ( P absolute claudication distance by 358 meters ( 80 % ) ( P walking economy by 11 % ( P 6-minute walk distance by 10 % ( P daily physical activity by 31 % , and maximal calf blood flow by 18 % ( P exercise rehabilitation ( P = NS ) , and were significantly greater than the changes in the control group throughout the study ( P Improvements in claudication distances , walking economy , 6-minute walk distance , physical activity level , and peripheral circulation after 6 months of exercise rehabilitation are sustained for an additional 12 months in older patients with intermittent claudication using a less frequent exercise maintenance program", "OBJECTIVE To compare the effect of two training programmes and advice to exercise at home on physiological adaptations in patients with peripheral arterial disease ( PAD ) . DESIGN 30 patients with a typical history of PAD and intermittent claudication were r and omised to either an upper body strength training programme ( UBST ) , a dynamic ( walking , cycling , circuit ) conventional exercise rehabilitation programme ( CER ) , or advice to ' walk as much as possible at home ' ( CONT ) . Before and after intervention groups performed a st and ard grade d treadmill exercise test ( GTET ) and a 6-minute walk test ( SMWT ) to determine peak physiological parameters and walking distances . Maximal walking distance ( MWD ) , pain-free walking distance ( PFWD ) , peak oxygen uptake ( VO2 ) , heart rate and perceived pain were measured . RESULTS MWD on the GTET increased significantly in the CER group compared with the CONT and UBST groups ( 93.9 + /- 79 % v. 7.0 + /- 19.8 % v. 7.3 + /- 46 % ; CER v. UBST v. CONT p = 0.003 ) . Similarly , peak VO2 increased with CER compared with the CONT and UBST groups ( 28.4 + /- 20 v. -6.2 + /- 15 v. -1.0 + /- 21 % ; CER v. UBST v. CONT p = 0.004 ) . During the SMWT the CER and UBST groups improved in PFWD compared with the CONT group ( 37 + /- 47 % v. 27 + /- 71 % v. -30 + /- 29 % ; CER v. UBST v. CONT p = 0.03 ) , and perceived pain decreased in the CER group compared with the UBST group ( -24 + /- 39 % v. 27 + /- 48 % ; CER v. UBST p = 0.01 ) . CONCLUSION CER improves physiological parameters and walking distances more than UBST does . CER is effective within 6 weeks . Verbal encouragement to exercise is an ineffective form of management", "PURPOSE The purpose of this r and omized trial was to compare the efficacy of a low-intensity exercise rehabilitation program vs a high-intensity program in changing physical function , peripheral circulation , and health-related quality of life in peripheral arterial disease ( PAD ) patients limited by intermittent claudication . METHODS Thirty-one patients r and omized to low-intensity exercise rehabilitation and 33 patients r and omized to high-intensity exercise rehabilitation completed the study . The 6-month exercise rehabilitation programs consisted of intermittent treadmill walking to near maximal claudication pain 3 days per week at either 40 % ( low-intensity group ) or 80 % ( high-intensity group ) of maximal exercise capacity . Total work performed in the two training regimens was similar by having the patients in the low-intensity group exercise for a longer duration than patients in the high-intensity group . Measurements of physical function , peripheral circulation , and health-related quality of life were obtained on each patient before and after the rehabilitation programs . RESULTS After the exercise rehabilitation programs , patients in the two groups had similar improvements in these measures . Initial claudication distance increased by 109 % in the low-intensity group ( P absolute claudication distance increased by 61 % ( P peak oxygen uptake , ischemic window , and health-related quality of life . CONCLUSION The efficacy of low-intensity exercise rehabilitation is similar to high-intensity rehabilitation in improving markers of functional independence in PAD patients limited by intermittent claudication , provided that a few additional minutes of walking is accomplished to elicit a similar volume of exercise", "OBJECTIVE The purpose of the study was to examine the effects of a 12-month exercise program on lower limb mobility ( temporal-spatial gait parameters and gait kinematics ) , walking performance , peak physiological responses , and physical activity levels in individuals with symptoms of intermittent claudication due to peripheral arterial disease ( PAD-IC ) . METHODS Participants ( n = 21 ) with an appropriate history of PAD-IC , ankle-brachial pressure index ( ABI ) Participants were r and omly allocated to either a control PAD-IC group ( CPAD-IC ) ( n = 11 ) that received st and ard medical therapy and a treatment PAD-IC group ( TPAD-IC ) ( n = 10 ) , which also took part in a 12-month supervised exercise program . A further group of participants ( n = 11 ) free of PAD ( ABI > 0.9 ) and who were non-regular exercisers were recruited from the community to act as age and mass matched controls ( CON ) . Lower limb mobility was determined via two-dimensional video motion analysis . A grade d treadmill test was used to assess walking performance and peak physiological responses to exercise . Physical activity levels were measured via a 7-day pedometer recording . Differences between groups were analyzed via repeated measures analysis of variance ( ANOVA ) . RESULTS The 12-month supervised exercise program had no significant effect on lower limb mobility , peak physiological responses , or physical activity levels in TPAD-IC compared with CPAD-IC participants . However , the TPAD-IC participants demonstrated significantly greater walking performance ( 171 % improvement in pain free walking time and 120 % improvement in maximal walking time compared with baseline ) . CONCLUSION The results of this study confirm that a 12-month supervised exercise program will result in improved walking performance , but does not have an impact on lower limb mobility , peak physiological responses , or physical activity levels of PAD-IC patients", "OBJECTIVES To compare the effect of unsupervised exercise , supervised exercise and intermittent pneumatic foot and calf compression ( IPC ) on the claudication distance , lower limb arterial haemodynamics and quality of life of patients with intermittent claudication . METHODS Thirty-four eligible patients with stable intermittent claudication were r and omised to IPC ( n = 13 , 3h/d for 6 months ) , supervised exercise ( n = 12 , three hourly sessions/week for 6 months ) or unsupervised exercise ( n = 9 ) . In each patient , initial claudication distance ( ICD ) , absolute claudication distance ( ACD ) , resting ankle brachial pressure index ( ABPI ) , and resting hyperaemic calf arterial inflow were measured before , 6 weeks , 6 months and 1 year after r and omisation . Quality of life was assessed with the short form (SF)-36 , walking impairment ( WIQ ) and intermittent claudication question naires ( ICQ ) . RESULTS Compared with unsupervised exercise , both IPC and supervised exercise , increased ICD and ACD , up to 2.83 times . IPC increased arterial inflow ( p ABPI . Supervised exercise decreased arterial inflow and increased ABPI ( p Unsupervised exercise had no effect on arterial inflow or ABPI . IPC improved significantly the ICQ score and the speed score of the WIQ , while supervised exercise improved the WIQ claudication severity score . At 1 year clinical effectiveness of supervised exercise and IPC was largely preserved . CONCLUSIONS IPC , by augmenting leg perfusion , achieved improvement in walking distance comparable with supervised exercise . Long-term results in a larger number of patients will provide valuable information on the optimal treatment modality of intermittent claudication", "PURPOSE This study was performed to test the efficacy of a supervised , hospital-based exercise program compared with a home-based exercise program involving minimal supervision , for both walking ability and quality of life measures in patients with exercise-limiting intermittent leg claudication . METHODS Twenty-one patients were assigned r and omly to 12 weeks of supervised exercise or to a home-based exercise group . After 12 weeks the participants in the supervised group transitioned to a home-based program . Both groups were then reevaluated at the end of 24 weeks . The initial claudication distance ( ICD ) and absolute claudication distance ( ACD ) on progressive treadmill exercise was measured at baseline , 12 weeks , and 24 weeks . Additionally , self-reported quality of life status was evaluated using the MOS SF-36 question naire . RESULTS Each group improved ( P ACD from baseline to 12 weeks , which was sustained at the 24-week follow-up . Both groups experienced similar long-term improvements ( P ACD ( 521.5 + /- 253.4 meters to 741.9 + /- 365.6 meters for the supervised group , 532.2 + /- 263.5 meters to 715.0 + /- 394.4 meters in the home group , P not significant , between groups ) . The supervised group experienced a greater improvement ( P ICD after 12 weeks than the home group but not at 24 weeks . The on-site group also experienced significant improvements in ICD after 24 weeks ( P self-reported physical function or mental health as assessed by the MOS SF-36 . CONCLUSION A structured exercise program was more effective in improving the ICD over a 24-week period than a less formal , home-based program . However , if patients are screened properly and receive adequate instruction , a home-based program can be a safe , low-cost alternative providing similar long-term ( 24 weeks ) exercise benefits in ACD", "BACKGROUND Although there have been many studies showing that exercise training is beneficial for patients with peripheral vascular occlusive disease ( PVOD ) , there is little research comparing various modes of training . Previous studies showed that exercise tests performed on a StairMaster ( StairMaster Sports/Medical Products , Kirkl and , WA ) produce responses similar to those elicited by treadmill tests . The purpose of this study was to compare these modes of exercise in a training program for patients with PVOD . METHODS Of the 23 eligible individuals who began the exercise program , 11 did not complete the regimen due to various complications . Thus , 12 patients were r and omly assigned to train for 12 weeks on either a StairMaster ( n = 6 ) or a treadmill ( n = 6 ) . Patients underwent progressive and single-stage exercise tests on both exercise modalities before and after training . RESULTS Mean exercise time before the onset of claudication pain for all tests rose significantly after training ( P treadmill exercise performance with less improvement noted when tested on the StairMaster , and vice versa ) . Exercise time to maximal pain increased for the training apparatus only ( P foot transcutaneous oxygen tension or the ankle-brachial blood pressure index . CONCLUSIONS Both StairMaster and treadmill training improve the exercise capacity of PVOD patients . The training effect is most apparent for the specific training apparatus , but there is some cross-over improvement to the other exercise modality . Thus , StairMaster training is appropriate and can be part of the exercise prescription for treatment of these patients", "PURPOSE In patients with intermittent claudication ( IC ) a structured walking exercise program improves exercise performance . However , few studies have evaluated the effects of exercise training on functional status during daily activities . We hypothesized that a supervised exercise training program would improve functional status in patients with IC , with 24 weeks of training more beneficial than 12 weeks . A secondary aim was to evaluate the effects of strength training and combinations of strength and treadmill training on functional status . METHODS Twenty-nine men with disabling IC were r and omized to 12 weeks of either supervised treadmill training ( 3 hr/wk at a work intensity sufficient to produce claudication ) , strength training ( 3 hr/wk of resistive training of six muscle groups of each leg ) , or to a nonexercising control group . Functional status was assessed by question naires characterizing walking ability ( Walking Impairment Question naire , WIQ ) , habitual physical activity level ( Physical Activity Recall , PAR ) , and physical , social , and role functioning , well-being , and overall health ( Medical Outcomes Study SF-20 , MOS ) . Patients alos had their activity levels monitored with an activity monitor ( Vitalog ) . RESULTS After 12 weeks of treadmill training PAR scores increased by 48 metabolic equivalent hr/wk , the MOS physical functioning score by 24 percentage points , and the number of bouts of walking activity measured by the Vitalog by 4.5 bouts/hr ( all p WIQ scores . After 12 additional weeks of treadmill training improvements initially observed in the PAR , MOS , and Vitalog scores were maintained , and in addition the ability to walk distances ( WIQ ) improved by 31 percentage points , and the IC severity score had improved by 29 percentage points ( both p strength training patients improved their WIQ walking speed , stair climbing scores , and MOS well-being scores with no other changes in functional status . Subjects in the control group did not improve functional status by any measure . Twelve weeks of treadmill training after the strength training program maintained WIQ walking speed scores , and activity level defined by Vitalog improved . Twelve weeks of combined treadmill and strength training after the control period had no effect on functional status . CONCLUSIONS A supervised treadmill training program improved functional status during daily activities , with 24 weeks more effective than 12 . In addition , treadmill training alone was more effective in improving functional status in patients with IC than strength training or combinations of the training modalities", "BACKGROUND To explore the efficacy of cycle training in the treatment of intermittent claudication , the present study compared performance and physiologic effects of cycle training with more conventional treadmill walking training in a group of patients with claudication . METHOD Forty-two individuals with peripheral arterial disease and intermittent claudication ( 24 men , 18 women ) were stratified by gender and the presence or absence of type 2 diabetes mellitus and then r and omized to a treadmill ( n = 13 ) , cycle ( n = 15 ) , or control group ( n = 14 ) . Treadmill and cycle groups trained three times a week for 6 weeks , whereas the control group did not train during this period . Maximal and pain-free exercise times were measured on grade d treadmill and cycle tests before and after training . RESULTS Treadmill training significantly improved maximal and pain-free treadmill walking times but did not improve cycle performance . Cycle training significantly improved maximal cycle time but did not improve treadmill performance . However , there was evidence of a stronger cross-transfer effect between the training modes for patients who reported a common limiting symptom during cycling and walking at baseline . There was also considerable variation in the training response to cycling , and a subgroup of responsive patients in the cycle group improved their walking performance by more than the average response observed in the treadmill group . CONCLUSION These findings suggest that cycle exercise is not effective in improving walking performance in all claudication patients but might be an effective alternative to walking in those who exhibit similar limiting symptoms during both types of exercise", "Introduction : Peripheral atherosclerotic disease ( PAD ) is a condition characterized by low functional capacity which is associated with impaired free living , ambulation and low exercise tolerance . The purpose of this r and omized controlled study was to evaluate whether changes in maximal walking time are associated with adaptations in cardiovascular function following supervised exercise", "Expansion of the capillary network , or angiogenesis , occurs following endurance training . This process , which is reliant on the presence of VEGF ( vascular endothelial growth factor ) , is an adaptation to a chronic mismatch between oxygen dem and and supply . Patients with IC ( intermittent claudication ) experience pain during exercise associated with an inadequate oxygen delivery to the muscles . Therefore the aims of the present study were to examine the plasma VEGF response to acute exercise , and to establish whether exercise training alters this response in patients with IC . In Part A , blood was collected from patients with IC ( n=18 ) before and after ( + 20 and + 60 min post-exercise ) a maximal walking test to determine the plasma VEGF response to acute exercise . VEGF was present in the plasma of patients ( 45.11+/-29.96 pg/ml ) and was unchanged in response to acute exercise . Part B was a training study to determine whether exercise training altered the VEGF response to acute exercise . Patients were r and omly assigned to a treatment group ( TMT ; n=7 ) that completed 6 weeks of high-intensity treadmill training , or to a control group ( CON ; n=6 ) . All patients completed a maximal walking test before and after the intervention , with blood sample s drawn as for Part A. Training had no effect on plasma VEGF at rest or in response to acute exercise , despite a significant increase in maximal walking time in the TMT group ( 915+/-533 to 1206+/-500 s ; P=0.009 ) following the intervention . The absence of a change in plasma VEGF may reflect altered VEGF binding at the endothelium , although this can not be confirmed by the present data", "CONTEXT Neither supervised treadmill exercise nor strength training for patients with peripheral arterial disease ( PAD ) without intermittent claudication have been established as beneficial . OBJECTIVE To determine whether supervised treadmill exercise or lower extremity resistance training improve functional performance of patients with PAD with or without claudication . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled clinical trial performed at an urban academic medical center between April 1 , 2004 , and August 8 , 2008 , involving 156 patients with PAD who were r and omly assigned to supervised treadmill exercise , to lower extremity resistance training , or to a control group . MAIN OUTCOME MEASURES Six-minute walk performance and the short physical performance battery . Secondary outcomes were brachial artery flow-mediated dilation , treadmill walking performance , the Walking Impairment Question naire , and the 36-Item Short Form Health Survey physical functioning ( SF-36 PF ) score . RESULTS For the 6-minute walk , those in the supervised treadmill exercise group increased their distance walked by 35.9 m ( 95 % confidence interval [ CI ] , 15.3 - 56.5 m ; P distance walked by 12.4 m ( 95 % CI , -8.42 to 33.3 m ; P = .24 ) compared with the control group . Neither exercise group improved its short physical performance battery scores . For brachial artery flow-mediated dilation , those in the treadmill group had a mean improvement of 1.53 % ( 95 % CI , 0.35%-2.70 % ; P = .02 ) compared with the control group . The treadmill group had greater increases in maximal treadmill walking time ( 3.44 minutes ; 95 % CI , 2.05 - 4.84 minutes ; P walking impairment distance score ( 10.7 ; 95 % CI , 1.56 - 19.9 ; P = .02 ) ; and SF-36 PF score ( 7.5 ; 95 % CI , 0.00 - 15.0 ; P = .02 ) than the control group . The resistance training group had greater increases in maximal treadmill walking time ( 1.90 minutes ; 95 % CI , 0.49 - 3.31 minutes ; P = .009 ) ; walking impairment scores for distance ( 6.92 ; 95 % CI , 1.07 - 12.8 ; P = .02 ) and stair climbing ( 10.4 ; 95 % CI , 0.00 - 20.8 ; P = .03 ) ; and SF-36 PF score ( 7.5 ; 95 % CI , 0.0 - 15.0 ; P = .04 ) than the control group . CONCLUSIONS Supervised treadmill training improved 6-minute walk performance , treadmill walking performance , brachial artery flow-mediated dilation , and quality of life but did not improve the short physical performance battery scores of PAD participants with and without intermittent claudication . Lower extremity resistance training improved functional performance measured by treadmill walking , quality of life , and stair climbing ability . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00106327", "OBJECTIVE To analyze the effects of strength training ( ST ) in walking capacity in patients with intermittent claudication ( IC ) compared with walking training ( WT ) effects . METHODS Thirty patients with IC were r and omized into ST and WT . Both groups trained twice a week for 12 weeks at the same rate of perceived exertion . ST consisted of three sets of 10 repetitions of whole body exercises . WT consisted of 15 bouts of 2-minute walking . Before and after the training program walking capacity , peak VO(2 ) , VO(2 ) at the first stage of treadmill test , ankle brachial index , ischemic window , and knee extension strength were measured . RESULTS ST improved initial claudication distance ( 358 + /- 224 vs 504 + /- 276 meters ; P total walking distance ( 618 + /- 282 to 775 + /- 334 meters ; P VO(2 ) at the first stage of treadmill test ( 9.7 + /- 2.6 vs 8.1 + /- 1.7 mL.kg(-1).minute ; P ischemic window ( 0.81 + /- 1.16 vs 0.43 + /- 0.47 mm Hg minute meters(-1 ) ; P = .04 ) , and knee extension strength ( 19 + /- 9 vs 21 + /- 8 kg and 21 + /- 9 vs 23 + /- 9 ; P Strength increases correlated with the increase in initial claudication distance ( r = 0.64 ; P = .01 ) and with the decrease in VO(2 ) measured at the first stage of the treadmill test ( r = -0.52 ; P = .04 and r = -0.55 ; P = .03 ) . Adaptations following ST were similar to the ones observed after WT ; however , patients reported lower pain during ST than WT ( P ST improves functional limitation similarly to WT but it produces lower pain , suggesting that this type of exercise could be useful and should be considered in patients with IC", "Because individuals with claudication pain secondary to peripheral arterial disease ( PAD ) are limited in both walking speed and duration , the benefits of walking exercise may be insufficient to yield a cardiovascular training effect . The objectives of this analysis were to determine whether polestriding exercise training , performed by persons with PAD , would improve exercise endurance , elicit a cardiovascular training benefit , and improve quality of life ( QoL ) . Persons ( n = 49 ) whose claudication pain limited their exercise capacity were r and omized into a 24-week polestriding training program ( n = 25 , 65.8 ± 7.1 years of age ) or a nonexercise attention control group ( n = 24 , 68.0 ± 8.6 years of age ) . Those assigned to the polestriding group trained 3 times weekly . Control group subjects came to the laboratory biweekly for ankle blood pressure measurements . A symptom-limited ramp treadmill test , ratings of perceived leg pain , and QoL data ( using the Short Form-36 ) were obtained at baseline and upon completion of training . After 24 weeks of polestriding training , subjects increased their exercise endurance from 10.3 ± 4.1 minute to 15.1 ± 4.5 minute . This was significantly greater than control group subjects whose exercise endurance declined ( from 11.2 ± 4.7 to 10.3 ± 4.7 minute ; P ( P ( P = .04 ) , rate pressure product ( P = .05 ) , oxygen uptake ( P = .016 ) , and perceived leg pain ( P = .02 ) and exercise time improved from the baseline symptom-limited treadmill test to the 6-month symptom-limited treadmill test in the polestriding group compared to the control group . The improvement in the physical component summary score of the Short Form-36 was also greater in the polestriding group ( P = .031 ) . Polestriding training significantly improved the clinical indicators of cardiovascular fitness and QoL , and decreased symptoms of claudication pain during exertion", "Arm cranking is a useful alternative exercise modality for improving walking performance in patients with intermittent claudication ; however , the mechanisms of such an improvement are poorly understood . The main aim of the present study was to investigate the effects of arm-crank exercise training on lower-limb O2 delivery in patients with intermittent claudication . A total of 57 patients with intermittent claudication ( age , 70+/-8 years ; mean+/-S.D. ) were r and omized to an arm-crank exercise group or a non-exercise control group . The exercise group trained twice weekly for 12 weeks . At baseline and 12 weeks , patients completed incremental tests to maximum exercise tolerance on both an arm-crank ergometer and a treadmill . Respiratory variables were measured breath-by-breath to determine peak VO2 ( O2 uptake ) and ventilatory threshold . Near-IR spectroscopy was used in the treadmill test to determine changes in calf muscle StO2 ( tissue O2 saturation ) . Patients also completed a square-wave treadmill-walking protocol to determine VO2 kinetics . A total of 51 patients completed the study . In the exercise group , higher maximum walking distances ( from 496+/-250 to 661+/-324 m ) and peak VO2 values ( from 17.2+/-2.7 to 18.2+/-3.4 ml.kg-1 of body mass.min-1 ) were recorded in the incremental treadmill test ( P time to minimum StO2 ( from 268+/-305 s to 410+/-366 s ) , a speeding of VO2 kinetics ( from 44.7+/-10.4 to 41.3+/-14.4 s ) and an increase in submaximal StO2 during treadmill walking ( P walking performance after arm-crank exercise training in patients with intermittent claudication is attributable , at least in part , to improved lower-limb O2 delivery", "OBJECTIVE To determine the effects of a 6-month exercise program on ambulatory function , free-living daily physical activity , peripheral circulation , and health-related quality of life ( QOL ) in disabled older patients with intermittent claudication . DESIGN Prospect i ve , r and omized controlled trial . SETTING University Medical ( Center and Veterans Affairs Medical Center , Baltimore , Maryl and . PARTICIPANTS Thirty-one of 61 patients with Fontaine stage II peripheral arterial occlusive disease ( PAOD ) were r and omized to exercise rehabilitation and 30 to usual-care control . Three patients from the exercise group and six patients from the control group dropped out , leaving 28 and 24 patients , respectively , completing the study in each group . INTERVENTION Six months of exercise rehabilitation . MEASUREMENTS Treadmill distance walked to onset of claudication and to maximal claudication , ambulatory function , peripheral circulation , perceived QOL , and daily physical activity . RESULTS Compliance with the exercise program was 73 % of the possible sessions . Exercise rehabilitation increased treadmill distance walked to onset of claudication by 134 % ( P maximal claudication by 77 % ( P walking economy by 12 % ( P = .003 ) , 6-minute walk distance by 12 % ( P maximal calf blood flow by 30 % ( P Changes in distance walked to maximal pain correlated with changes in walking economy ( r = -.50 , P = .013 ) and changes in maximal calf blood flow ( r = .38 , P = .047 ) . Exercise rehabilitation increased accelerometer-derived daily physical activity by 38 % ( P distance walked to maximal pain ( r = .45 , P = .020 ) . These improvements were significantly better than the changes in the control group ( P exercise rehabilitation in older PAOD patients are dependent on improvements in peripheral circulation and walking economy . Improvement in treadmill claudication distances in these patients translated into increased accelerometer-derived physical activity in the community , which enabled the patients to become more functionally independent", "OBJECTIVES To investigate the effects of a 24-week program of upper- and lower-limb aerobic exercise training on walking performance in patients with symptomatic peripheral arterial disease ( PAD ) and to study the mechanisms that could influence symptomatic improvement . METHODS After approval from the North Sheffield Local Research Ethics Committee , 104 patients ( median age , 69 years ; range , 50 to 85 years ) with stable PAD were r and omized into an upper- or lower-limb aerobic exercise training group ( UL-Ex or LL-Ex ) , or to a nonexercise training control group . Training was performed twice weekly for 24 weeks at equivalent relative exercise intensities . An incremental arm- and leg-crank test ( ACT and LCT ) to maximum exercise tolerance was performed before and at 6 , 12 , 18 , and 24 weeks of the intervention to determine peak oxygen consumption ( VO(2 ) ) . Walking performance , defined as the claudicating distance ( CD ) and maximum walking distance ( MWD ) achieved before intolerable claudication pain , was assessed at the same time points by using a shuttle-walk protocol . Peak blood lactate concentration , Borg ratings of perceived exertion ( RPE ) and pain category ratio ( CR-10 ) were recorded during all assessment s. RESULTS CD and MWD increased over time ( P CD had improved by 51 % and 57 % , and MWD had improved by 29 % and 31 % ( all P peak heart rate at MWD in the UL-Ex group ( 109 + /- 4 vs 115 + /- 4 beats/min ; P amount of pain experienced in both groups ( P cardiovascular stress and an increased intensity of claudication pain before test termination after training . Patients assigned to exercise training also showed an increase in LCT peak VO2 at the 24-week time point in relation to baseline ( P ACT peak VO2 was only improved in the UL-Ex group ( P upper-limb aerobic exercise training in patients with PAD . Furthermore , that both arm- and leg-crank training could be useful exercise training modalities for improving cardiovascular function , walking performance , and exercise pain tolerance in patients with symptomatic PAD", "The purpose of this study was to investigate the effects of a progressive resistance training program on myosin heavy chain isoform expression , fiber type , and capillarization in patients with symptomatic peripheral arterial disease . Patients were r and omized to either a training group ( n = 11 , mean + /- SD , 70 + /- 6 years , 4 men , 7 women ) or a control group ( n = 9 , 66 + /- 6 years , 5 men , 4 women ) . The training sessions were completed 3 times/week , using 2 sets of various exercises , each performed for 8 - 15 repetitions . Muscle biopsies were obtained before and after 24 weeks from the medial gastrocnemius . Following the 24-week training program , the training group had significantly decreased the percentage of myosin heavy chain type IIB . The proportion of type IIB/AB fibers as measured by using myosin adenosine triphosphatase histochemistry decreased significantly in the training group . There were significant increases in type I and type II fiber areas , and capillary density also increased significantly in the training group . There were significant increases in 10 repetition maximum leg press and calf press strengths in the trained subjects . There were no significant changes in any of the measurements in the control group . It is concluded that progressive resistance training results in significant increases in muscle strength and alters skeletal muscle composition of subjects with peripheral arterial disease", "Abstract The efficacy of treadmill walking training to improve pain-free ( PFWD ) and maximal ( MWD ) walking distance in patients with claudication is well documented . The effects of aerobic arm-ergometry to improve PFWD and MWD compared to treadmill walking or usual care are not known . Forty-one participants ( 29 male , 12 female , mean age 67.7 years , 92.7 % smoking history , 36.6 % with diabetes ) with lifestyle-limiting claudication were r and omized to 12 weeks of 3 hours/week of supervised exercise training using either arm-ergometry , treadmill walking , or a combination , versus control . PFWD and MWD were assessed before and after training , and after 12 weeks of follow-up . The 12-week MWD increased significantly in the arm-ergometry ( + 53 % ) , treadmill ( + 69 % ) , and combination ( + 68 % ) groups ( p 24-week MWD was maintained in the arm-ergometry ( p = 0.009 ) and treadmill ( p = 0.019 ) groups , whereas the combination group declined ( p = 0.751 ) versus control . The 12-week PFWD increased significantly in the arm-ergometry group ( + 82 % ; p = 0.025 versus control ) . Change in PFWD in treadmill ( + 54 % ; p = 0.196 versus control ) and combination ( + 60 % ; p = 0.107 versus control ) groups did not reach statistical significance . PFWD improvement was maintained in the arm-ergometry group after a 12-week follow-up ( + 123 % ; p = 0.011 versus control ) . In conclusion , these pilot data demonstrate for the first time that dynamic arm exercise training can improve walking capability in people with peripheral arterial disease (PAD)-induced claudication compared to participants receiving usual care and that improvement was not different from that seen with treadmill walking exercise training . Dynamic arm exercise may be a therapeutic exercise option for patients with PAD", "PURPOSE To compare treadmill and shuttle walk tests for assessing functional capacity in patients with intermittent claudication , with respect to test-retest reliability , cardiovascular responses , and patient preferences . METHODS Patients with stable intermittent claudication ( N = 55 , ages 52 - 85 yr , median age 68 yr ) were recruited from the Sheffield Vascular Institute at the Northern General Hospital , Sheffield , UK . Each patient performed an incremental shuttle walk test , a constant-pace shuttle walk test , and a st and ardized treadmill test ( 3.2 km x h(-1 ) , 12 % gradient ) , each on three occasions . The incremental shuttle walk began at 3 km x h(-1 ) and increased by 0.5 km x h(-1 ) every minute , whereas the constant-pace shuttle walk was performed at the fixed pace of 4 km x h(-1 ) . Claudication distance ( CD ) , maximum walking distance ( MWD ) , heart rate ( HR ) , and blood pressure were assessed in each testing session . The patients also completed a test preference question naire . RESULTS CD and MWD for both shuttle walks were greater than the corresponding walking distances achieved in the treadmill test ( P Average coefficients of variation for repeated incremental shuttle walk , constant-pace shuttle walk , and treadmill tests were 15.9 % , 21.1 % , and 18.7 % , respectively , for MWD , corresponding to average intraclass correlation coefficients of 0.87 , 0.82 , and 0.87 . Treadmill walking evoked greater increases in HR and blood pressure ( P preference for it ( 24 vs 43 % for shuttle walking ) . CONCLUSION These findings indicated that shuttle walk testing exhibits similar test-retest reliability as treadmill testing , but that it evoked a lower level of cardiovascular stress and is preferred to treadmill testing by a large proportion of patients", "OBJECTIVE To determine the effects of 12-week exercise programme on ambulatory function , free-living daily physical activity and health-related quality of life in disabled older patients with intermittent claudication . DESIGN Prospect i ve , r and omized controlled trial . SETTING University Medical Center and Veterans Affairs Medical Center , Taipei , Taiwan . SUBJECTS Thirty-two of 64 patients with Fontaine stage II peripheral arterial occlusive disease ( PAOD ) were r and omized to exercise training and 32 to usual care control . Five patients from the exercise group and six patients from the control group dropped out , leaving 27 and 26 patients , respectively , completing the study in each group . INTERVENTIONS Twelve weeks of treadmill exercise training . MAIN OUTCOME MEASURES Treadmill walking time to onset of claudication pain and to maximal claudication pain , 6-min walk distance , self-reported ambulatory ability and perceived health-related quality of life ( QOL ) . RESULTS Compliance of exercise programme was 83 % of the possible sessions . Exercise training increased treadmill walking time to onset of claudication pain by 88 % ( P time to maximal pain by 70 % ( P 6-min walk distance by 21 % ( P Perception of health-related QOL improved from 12 % to 178 % in the exercise group . These improvements were significantly better than the changes in the control group ( P claudication following 12-week exercise training in elderly PAOD patients were observed . Increase in treadmill walking time to maximal claudication pain in these patients translated into the improvement of perceived physical health , which enabled the patients to become more functionally independent", "Objective . Current guidelines for treatment of intermittent claudication ( IC ) do not include a specific recommendation for the intensity of exercise therapy . Thus , the purpose of this study was to determine the relative effectiveness of high versus low intensity exercise for patients with IC , and further to study the effect of such training on blood flow to the legs during exercise . Design . The effect of eight weeks of supervised endurance training was examined in 16 patients with IC . The patients were r and omly assigned to training at intensities corresponding to either 60 % or 80 % of their peak oxygen consumption ( VO2peak ) , respectively . Results . VO2peak and time to exhaustion increased significantly ( 9 % and 16 % , respectively ) more in the high intensity group ( p Blood flow to the legs did not change after training in any of the groups . Conclusion . High intensity training gave larger improvements in VO2peak and time to exhaustion than low intensity training . As blood flow did not change after the exercise program , it is likely that the observed different increase of VO2peak was due to changed mitochondrial oxidative capacity and /or skeletal muscle diffusive capacity", "OBJECTIVE The initial treatment for intermittent claudication is supervised exercise therapy ( SET ) . Owing to limited capacity and patient transports costs of clinic-based SET , a concept of SET provided by local physiotherapists was developed . We hypothesized that provision of daily feedback with an accelerometer in addition to SET would further increase walking distance . METHODS This multicenter r and omized trial was set in vascular surgery outpatient clinics and included 304 patients with intermittent claudication . Patients were r and omized to exercise therapy in the form of \" go home and walk \" advice ( WA ) , SET , or SET with feedback . Local physiotherapists provided SET . The primary outcome measure was the change in absolute claudication distance . Secondary outcomes were the change in functional claudication distance and results on the Walking Impairment Question naire ( WIQ ) and Short-Form 36 ( SF-36 ) Health Survey after 12 months . RESULTS In 11 centers , 102 , 109 , and 93 patients were included , respectively , in the WA , SET , and SET with feedback groups , and data for 83 , 93 , and 76 , respectively , could be analyzed . The median ( interquartile range ) change in walking distance between 12 months and baseline in meters was 110 ( 0 - 300 ) in the WA group , 310 ( 145 - 995 ) in the SET group , and 360 ( 173 - 697 ) in the SET with feedback group ( P WIQ scores and relevant domains of the SF-36 improved statistically significantly in the SET groups . CONCLUSIONS SET is more effective than WA in improving walking distance , WIQ scores , and quality of life for patients with intermittent claudication . Additional feedback with an accelerometer did not result in further improvement . SET programs should be made available for all patients with intermittent claudication" ]	411899ce-06ff-11f0-808a-c43d1ab1c353
Background Cardiorespiratory fitness is a strong predictor of all-cause mortality . Physical activity of at least moderate intensity can improve cardiorespiratory fitness . Workplaces may provide a relatively controlled setting in which to improve cardiorespiratory fitness through physical activity . Limited work has been conducted to quantify the impact of delivering physical activity in the workplace on cardiorespiratory fitness . Objective The objective of this systematic review was to quantify the effects of workplace physical activity interventions on peak oxygen consumption ( VO2peak ) and explore study and participant characteristics as putative moderators . Methods Seven data bases were search ed up to September 2018 . Search terms included “ workplace ” , “ physical activity ” and “ intervention ” . Inclusion criteria were controlled trials where physical activity of at least moderate intensity was delivered in the workplace and compared to controls or non-active comparators ; and cardiorespiratory fitness measured by actual or predicted VO2peak . Risk of bias was assessed using the PEDro scale . A r and om-effects meta- analysis was conducted with between- study variation quantified and then explored for putative predictors with a meta-regression . Pooled estimate uncertainty was expressed as 90 % confidence intervals ( CIs ) and assessed against our threshold value for clinical relevance of 1 mL·kg−1·min−1 . Results The final data set consisted of 25 estimates of VO2peak from 12 trials . The pooled mean differences between intervention and control arms was a beneficial improvement of 2.7 mL·kg−1·min−1 ( 90 % CI 1.6–3.8 ) . The 95 % prediction interval ranged from a reduction in VO2peak of − 1.1 to an improvement of 6.5 mL·kg−1·min−1 . Between- study heterogeneity ( τau ) was ± 1.6 mL·kg−1·min−1 . The meta-regression showed longer interventions ( 3.2 mL·kg−1·min−1 ; 90 % CI 1.6–3.8 ) to have an additive effect and studies with a low risk of bias ( − 2.5 mL·kg−1·min−1 ; 90 % CI − 4.0 to − 1.0 ) , and participants of greater baseline VO2peak ( − 1.6 mL·kg−1·min−1 ; 90 % CI − 3.6 to 0.4 ) , and age ( − 1.4 mL·kg−1·min−1 ; 90 % CI − 3.2 to 0.3 ) having a lesser effect . Participant sex ( percentage female ) had an additive effect on VO2peak ( 0.4 mL·kg−1·min−1 ; 90 % CI − 1.6 to 2.4 ) . Conclusions Workplace-based physical activity interventions consisting of at least moderate-intensity activity improve cardiorespiratory fitness . At the present time , we surmise that no single group of employees ( e.g. older employees or less fit individuals ) can be definitively identified as st and ing to benefit more from workplace physical activity interventions than others . This demonstrates the potential utility of workplace physical activity interventions for improving cardiorespiratory fitness in a broad range of healthy employees . Protocol registration : PROSPERO ( registration number : 42017057498 )	[ "Background The heterogeneity statistic I2 , interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error , depends on precision , that is , the size of the studies included . Methods Based on a real meta- analysis , we simulate artificially ' inflating ' the sample size under the r and om effects model . For a given inflation factor M = 1 , 2 , 3 , ... and for each trial i , we create a M-inflated trial by drawing a treatment effect estimate from the r and om effects model , using si2MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi = xH8viVGI8Gi = hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY = rqGqVepae9pg0db9vqaiVgFr0xfr = xfr = xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4Cam3aa0baaSqaaiabdMgaPbqaaiabikdaYaaaaaa@2FBE@/M as within-trial sampling variance . Results As precision increases , while estimates of the heterogeneity variance τ2 remain unchanged on average , estimates of I2 increase rapidly to nearly 100 % . A similar phenomenon is apparent in a sample of 157 meta-analyses . Conclusion When deciding whether or not to pool treatment estimates in a meta- analysis , the yard-stick should be the clinical relevance of any heterogeneity present . τ2 , rather than I2 , is the appropriate measure for this purpose", "OBJECTIVE It is unknown if aerobic exercise overloads or improves the cardiovascular system among workers with high occupational physical activity . This was investigated in a worksite r and omized controlled trial ( RCT ) of aerobic exercise among cleaners . METHODS We r and omized 116 cleaners between 18 - 65 years . The aerobic exercise group ( N=57 ) performed worksite aerobic exercise ( 30 minutes twice a week ) and the reference group ( N=59 ) received lectures . Cardiorespiratory fitness , blood pressure ( BP ) and diurnal heart rate ( HR ) for measuring aerobic workload [ % HR reserve ( % HRR ) ] were collected at baseline and after four months . A repeated measure 2 × 2 multi-adjusted mixed-model design was applied to compare the between-group differences in an intention-to-treat analysis . RESULTS Between-group differences ( P : cardiorespiratory fitness 2.2 [ st and ard error ( SE ) 0.8 ] ml O 2 × min -1 × kg -1 [ 95 % confidence interval ( 95 % CI ) 0.6 - 3.8 ] , aerobic workload - 3.5 ( SE 1.2 ) % HRR ( 95 % CI - 5.9- -1.0 ) , resting HR -3.8 ( SE 1.2 ) bpm ( 95 % CI -6.1- - 1.4 ) , sleeping HR -3.8 ( SE 1.1 ) bpm ( 95 % CI - 5.9- - 1.7 ) , and systolic BP 3.6 ( SE 1.3 ) mmHg ( 95 % CI 1.1 - 6.0 ) . CONCLUSIONS Worksite aerobic exercise seems to improve cardiorespiratory fitness , aerobic workload , and resting and sleeping HR , but increase systolic BP among cleaners . Beneficial physiological cardiovascular effects are seen from aerobic exercise , but also a harmful effect is evident . Therefore , recommendations should take into consideration the potential cardiovascular overload from additional aerobic exercise on workers with high levels of occupational physical activity", "Aim Intervention fidelity refers to the degree to which an experimental manipulation has been implemented as intended , but simple , robust methods for quantifying fidelity have not been well documented . Therefore , we aim to illustrate a rigorous quantitative evaluation of intervention fidelity , using data collected during a high-intensity interval training intervention . Design Single-group measurement study . Methods Seventeen adolescents ( mean age ± st and ard deviation [ SD ] 14.0 ± 0.3 years ) attended a 10-week high-intensity interval training intervention , comprising two exercise sessions per week . Sessions consisted of 4 - 7 45-s maximal effort repetitions , interspersed with 90-s rest . We collected heart rate data at 5-s intervals and recorded the peak heart rate for each repetition . The high-intensity exercise criterion was ≥90 % of individual maximal heart rate . For each participant , we calculated the proportion of total exercise repetitions exceeding this threshold . A linear mixed model was applied to properly separate the variability in peak heart rate between- and within-subjects . Results are presented both as intention to treat ( including missed sessions ) and per protocol ( only participants with 100 % attendance ; n=8 ) . Results For intention to treat , the median ( interquartile range ) proportion of repetitions meeting the high-intensity criterion was 58 % ( 42 % to 68 % ) . The mean peak heart rate was 85 % of maximal , with a between-subject SD of 7.8 ( 95 % confidence interval 5.4 to 11.3 ) percentage points and a within-subject SD of 15.1 ( 14.6 to 15.6 ) percentage points . For the per protocol analysis , the median proportion of high-intensity repetitions was 68 % ( 47 % to 86 % ) . The mean peak heart rate was 91 % of maximal , with between- and within-subject SDs of 3.1 ( -1.3 to 4.6 ) and 3.4 ( 3.2 to 3.6 ) percentage points , respectively . Conclusions Synthesis ing information on exercise session attendance and compliance ( exercise intensity ) quantifies the intervention dose and informs evaluations of treatment fidelity", "Background Although the hazardous health effects of a sedentary lifestyle are well known , many adults struggle with regular physical activity . Simple and efficient encouragements for increased physical activity are needed . Objective To determine the effect on cardiovascular health of email-based encouragements to do daily stair-walks at work together with colleagues among adults in sedentary occupations . Methods A single-blind r and omized controlled trial was performed at a large administrative company in Copenhagen , Denmark . Participants were 160 office workers ( 125 women , 35 men ; mean age 42 years , SD 10 ; sitting 89.5 % of work time ) . At baseline , aerobic fitness was 37 mL/min/kg ( SD 9 ) , mean blood pressure was 118/79 mmHg ( SD 14/9 ) , and mean body mass index ( BMI ) was 23 kg/m2 ( SD 4 ) . Participants were r and omly assigned ( 2:1 ratio ) to an email group receiving weekly email-based encouragements to walk the stairs for 10 minutes a day or to a control group receiving weekly reminders to continue their usual physical activities . The primary outcome was the change from baseline to 10-week follow-up in aerobic fitness determined from a maximal cycle test . The examiner was blinded to group allocation . Results Adherence to the email encouragements was fairly high with 82.7 % of the participants performing at least 3 sessions of 10-minute stair-walks per week ( mean 3.3 , SD 1.3 ) . Mean heart rate reached 167 beats/min ( SD 10 ) during stair-walks . In the intention-to-treat analysis , aerobic fitness increased 1.45 mL/min/kg ( 95 % CI 0.64 - 2.27 ) at 10-week follow-up in the email group compared with the control group . In participants with low aerobic fitness at baseline ( n=56 ) , aerobic fitness increased 1.89 mL/min/kg ( 95 % CI 0.53 - 3.24 ) , and systolic and diastolic blood pressure decreased 4.81 mmHg ( 95 % CI 0.47 - 9.16 ) and 2.67 mmHg ( 95 % CI 0.01 - 5.32 ) , respectively , in the email group compared with the control group . Body weight decreased in the email group of those with low aerobic fitness compared with the control group , but this was not statistically significant . Conclusions Simple and inexpensive email-based encouragements to do daily stair-walks together with colleagues at work improves cardiovascular health among adults in sedentary occupations . There exists an enormous potential to prevent the hazardous health effects of a sedentary lifestyle through the use of email-based encouragements to do short bouts of physical activity at the workplace . Trial Registration Clinical trials.gov NCT01293253 ; http:// clinical trials.gov/ct2/show/NCT01293253 ( Archived by WebCite at http://www.webcitation.org/6HWG2jw68 )", "OBJECTIVES The combination of high physical work dem and s and low physical capacity has been shown to increase the risk for cardiovascular disease and musculoskeletal disorders . The aim of this study was to assess the physical capacity of construction workers and evaluate the effect of individually tailored exercise programs on their physical fitness and muscular capacity . METHOD The study was a r and omized controlled trial of male constructions workers allocated to either an exercise or control group . The intervention lasted 12 weeks , and the exercise group trained 3 x 20 minutes a week . The participants completed health checks before and after the intervention period . Data from the first health check were used to tailor the exercise in the interventions . RESULTS At baseline , participants had maximal oxygen consumption ( VO(2max ) ) of 2.9 [ st and ard deviation ( SD ) 0.7 ] l/min and body mass index ( BMI ) of 28.3 ( SD 4.7 ) . Compared to representative data on employees in Denmark ( N=78 ) , this study population ( N=67 ) had significantly lower relative aerobic capacity [ difference in z-score -1.13 , st and ard error ( SE ) 0.1 , P higher BMI [ difference in z-score 1.10 , SE 0.2 , P VO(2max)of 0.4 l/min for the exercise group and 0.0 l/min for the control group ( P Body mass and other general health measures remained unchanged . CONCLUSION Training for 20 minutes , 3 times a week significantly increased VO(2max)with a clinical ly relevant magnitude regarding risk of cardiometabolic disorders . This study demonstrates a good effectiveness for integrating short exercise bouts into organizational routines among constructions workers", "OBJECTIVE The aim of this trial was to investigate the effectiveness of a worksite intervention using kettlebell training to improve musculoskeletal and cardiovascular health . METHODS This single-blind r and omized controlled trial involved 40 adults from occupations with a high prevalence of reported musculoskeletal pain symptoms ( mean age 44 years , body mass index 23 kg/m² , 85 % women , with pain intensity of the neck/shoulders 3.5 and of the low back 2.8 on a scale of 0 - 10 ) . A blinded assessor took measures at baseline and follow-up . Participants were r and omly assigned to training -- consisting of ballistic full-body kettlebell exercise 3 times per week for 8 weeks -- or a control group . The main outcome measures were pain intensity of the neck/shoulders and low back , isometric muscle strength , and aerobic fitness . RESULTS Compared with the control group , pain intensity of the neck/shoulders decreased 2.1 points [ 95 % confidence interval ( 95 % CI ) -3.7- -0.4 ] and pain intensity of the low back decreased 1.4 points ( 95 % CI -2.7- -0.02 ) in the training group . Compared with the control group , the training group increased muscle strength of the trunk extensors ( P trunk flexors and shoulders . Aerobic fitness remained unchanged . CONCLUSIONS Worksite intervention using kettlebell training reduces pain in the neck/shoulders and low back and improves muscle strength of the low back among adults from occupations with a high prevalence of reported musculoskeletal pain symptoms . This type of training does not appear to improve aerobic fitness", "BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from \" fair \" to \" substantial , \" and the reliability of the total PEDro score was \" fair \" to \" good .", "Despite its obvious advantages , few studies have examined health outcomes of regular stariclimbing . In this study , we investigated the training effects of eight weeks of stairclimbing on recognised measures of health-related fitness in an occupational setting . Forty-five public sector employees ( 22 male , 23 female ) aged 42.3 ± 9.0 years were r and omly assigned to control ( n = 16 ) or stairclimbing ( n = 29 ) groups . Stairclimbing training began with 1 bout 5d·wk(-1 ) in week 1 , increasing by one climb per day every two weeks until week 5 , where a maintenance level of 3 climbs per day was reached . Participants climbed on staircases located within an 8 storey office block , consisting of 145 steps . The prescribed exercise intensity involved climbing the 8 flights of stairs at a rate of 75 steps·min(-1 ) . All participants agreed not to change their diet or lifestyle over the experimental period . Relative to controls , the stairclimbing group showed a significant increase of 9.4 % in predicted VO2max ( p changes in blood pressure , blood lipid concentrations or body composition were noted . These findings provide evidence that stairclimbing can enhance an important component of health-related fitness , namely cardiovascular fitness . Given that such improvement result ed from less than 30 minutes per week of moderate exercise , stairclimbing in the workplace should be promoted as a health-enhancing physical activity . Key pointsLow volumes of stairclimbing significantly increased a key component of cardiorespiratory fitness , namely VO2max . Stairclimbing can therefore be promoted within the typical urban workplace as a health enhancing activity . Indices of morphological or metabolic fitness may require larger volumes of stairclimbing than as prescribed in the current study", "OBJECTIVES The primary aim of this study was to examine the impact of physical activity ( PA ) in the natural environment ( eg , \" green exercise \" ) on resting autonomic function in the Walks4Work intervention . A secondary aim was to assess the feasibility of Walks4Work in terms of adherence , change in PA levels , and cardiovascular health parameters . METHODS In an 8-week r and omized control trial , 94 office workers in an international company were allocated to one of three groups : control , nature ( NW ) , or built ( BW ) lunchtime walking route . Both walking groups were required to undertake two lunchtime walks each week . The NW route centered around trees , maintained grass , and public footpaths . In contrast , the BW consisted of pavement routes through housing estates and industrial areas . Data were collected at baseline and following the intervention . To investigate the impact of the intervention , mixed- design analysis of variance ( ANOVA ) were performed . RESULTS A total of 73 participants completed the intervention ( drop-out rate of 22 % ) . No difference was observed in resting autonomic function between the groups . Self-reported mental health improved for the NW group only . PA levels increased at the intervention mid-point for all groups combined but adherence to the intervention was low with rates of 42 % and 43 % within the BW and NW groups , respectively . CONCLUSION Accompanying a guideline of two active lunchtimes per week with low facilitator input appears inadequate for increasing the number of active lunchtimes and modifying cardiovascular health parameters in an office population . However , this population fell within normal ranges for cardiovascular measures and future research should consider investigating at-risk population s , particularly hypertensive individuals", "Learning points R and omised controlled trials ( RCTs ) are the reference st and ard for study ing causal relationships between interventions and outcomes as r and omisation eliminates much of the bias inherent with other study design s. To provide a true , reliable assessment of effectiveness , RCTs need to be conducted robustly , i.e. with concealment of allocation , blinding , intention-to-treat analysis and sufficiently large sample size", "Objective : The aim of this study was to assess the effectiveness of a workplace leg-strengthening program on self-reported function , physical capacity , and work-related outcomes among desk-based workers . Methods : Forty-three desk-based workers were r and omized to a 12-week exercise program or no exercise control . The primary outcome was change in self-reported physical function on the Lower Extremity Functional Scale ( LEFS ) from baseline to follow-up . Secondary outcomes were physical capacity ( mobility , strength ) , self-reported outcomes ( pain , depressive symptoms ) , and work-related outcomes ( resilience , work ability ) . Results : The exercise group showed greater improvements in LEFS and mobility . No significant between-group differences existed in knee strength or remaining self-reported and work-related outcomes . Conclusion : Workplace implemented leg-strengthening exercises are effective at improving self-reported and physical health outcomes of desk-based workers . Moving forward , occupational exercise interventions may be essential to enhance worker longevity among the aging , sedentary workforce" ]	41189a0a-06ff-11f0-808a-c43d1ab1c353
BACKGROUND The evidence on whether vitamin D supplementation is effective in decreasing cancers is contradictory . OBJECTIVES To assess the beneficial and harmful effects of vitamin D supplementation for prevention of cancer in adults . SEARCH METHODS We search ed the Cochrane Central Register of Controlled Trials ( CENTRAL ) , MEDLINE , EMBASE , LILACS , Science Citation Index Exp and ed , and the Conference Proceedings Citation Index-Science to February 2014 . We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials . SELECTION CRITERIA We included r and omised trials that compared vitamin D at any dose , duration , and route of administration versus placebo or no intervention in adults who were healthy or were recruited among the general population , or diagnosed with a specific disease . Vitamin D could have been administered as supplemental vitamin D ( vitamin D₃ ( cholecalciferol ) or vitamin D₂ ( ergocalciferol ) ) , or an active form of vitamin D ( 1α-hydroxyvitamin D ( alfacalcidol ) , or 1,25-dihydroxyvitamin D ( calcitriol ) ) . DATA COLLECTION AND ANALYSIS Two review authors extracted data independently . We conducted r and om-effects and fixed-effect model meta-analyses . For dichotomous outcomes , we calculated the risk ratios ( RRs ) . We considered risk of bias in order to assess the risk of systematic errors . We conducted trial sequential analyses to assess the risk of r and om errors . MAIN RESULTS Eighteen r and omised trials with 50,623 participants provided data for the analyses . All trials came from high-income countries . Most of the trials had a high risk of bias , mainly for-profit bias . Most trials included elderly community-dwelling women ( aged 47 to 97 years ) . Vitamin D was administered for a weighted mean of six years . Fourteen trials tested vitamin D₃ , one trial tested vitamin D₂ , and three trials tested calcitriol supplementation . Cancer occurrence was observed in 1927/25,275 ( 7.6 % ) recipients of vitamin D versus 1943/25,348 ( 7.7 % ) recipients of control interventions ( RR 1.00 ( 95 % confidence interval ( CI ) 0.94 to 1.06 ) ; P = 0.88 ; I² = 0 % ; 18 trials ; 50,623 participants ; moderate quality evidence according to the GRADE instrument ) . Trial sequential analysis ( TSA ) of the 18 vitamin D trials shows that the futility area is reached after the 10th trial , allowing us to conclude that a possible intervention effect , if any , is lower than a 5 % relative risk reduction . We did not observe substantial differences in the effect of vitamin D on cancer in subgroup analyses of trials at low risk of bias compared to trials at high risk of bias ; of trials with no risk of for-profit bias compared to trials with risk of for-profit bias ; of trials assessing primary prevention compared to trials assessing secondary prevention ; of trials including participants with vitamin D levels below 20 ng/mL at entry compared to trials including participants with vitamin D levels of 20 ng/mL or more at entry ; or of trials using concomitant calcium supplementation compared to trials without calcium . Vitamin D decreased all-cause mortality ( 1854/24,846 ( 7.5 % ) versus 2007/25,020 ( 8.0 % ) ; RR 0.93 ( 95 % CI 0.88 to 0.98 ) ; P = 0.009 ; I² = 0 % ; 15 trials ; 49,866 participants ; moderate quality evidence ) , but TSA indicates that this finding could be due to r and om errors . Cancer occurrence was observed in 1918/24,908 ( 7.7 % ) recipients of vitamin D₃ versus 1933/24,983 ( 7.7 % ) in recipients of control interventions ( RR 1.00 ( 95 % CI 0.94 to 1.06 ) ; P = 0.88 ; I² = 0 % ; 14 trials ; 49,891 participants ; moderate quality evidence ) . TSA of the vitamin D₃ trials shows that the futility area is reached after the 10th trial , allowing us to conclude that a possible intervention effect , if any , is lower than a 5 % relative risk reduction . Vitamin D₃ decreased cancer mortality ( 558/22,286 ( 2.5 % ) versus 634/22,206 ( 2.8 % ) ; RR 0.88 ( 95 % CI 0.78 to 0.98 ) ; P = 0.02 ; I² = 0 % ; 4 trials ; 44,492 participants ; low quality evidence ) , but TSA indicates that this finding could be due to r and om errors . Vitamin D₃ combined with calcium increased nephrolithiasis ( RR 1.17 ( 95 % CI 1.03 to 1.34 ) ; P = 0.02 ; I² = 0 % ; 3 trials ; 42,753 participants ; moderate quality evidence ) . TSA , however , indicates that this finding could be due to r and om errors . We did not find any data on health-related quality of life or health economics in the r and omised trials included in this review . AUTHORS ' CONCLUSIONS There is currently no firm evidence that vitamin D supplementation decreases or increases cancer occurrence in predominantly elderly community-dwelling women . Vitamin D₃ supplementation decreased cancer mortality and vitamin D supplementation decreased all-cause mortality , but these estimates are at risk of type I errors due to the fact that too few participants were examined , and to risks of attrition bias originating from substantial dropout of participants . Combined vitamin D₃ and calcium supplements increased nephrolithiasis , whereas it remains unclear from the included trials whether vitamin D₃ , calcium , or both were responsible for this effect . We need more trials on vitamin D supplementation , assessing the benefits and harms among younger participants , men , and people with low vitamin D status , and assessing longer duration of treatments as well as higher dosages of vitamin D. Follow-up of all participants is necessary to reduce attrition bias	[ "An unexplained loss of muscle strength occurs with aging . Vitamin D deficiency can cause myopathy and administration of 1,25-dihydroxyvitamin D3 [ 1,25-(OH2)D3 ] to persons with low serum concentrations can improve strength . To test the hypothesis that the weakness associated with aging is in part due to inadequate serum concentrations of [ 1,25-(OH2)D3 ] , we conducted a r and omized , controlled , double blinded trial in 98 men and women volunteers over 69 yr old . Treatment consisted of 0.25 micrograms 1,25-(OH)2D3 , orally , twice per day or identical placebo for 6 months . Leg muscle strength of the quadriceps was measured with an isokinetic dynamometer . There was no difference between the two groups at 1 week , 1 month , or 6 months of treatment in any of the measures of muscle strength . We conclude that oral administration of 0.5 micrograms 1,25-(OH)2D3/day does not improve muscle strength in older persons . Further research is needed to determine the etiology of the decline in muscle strength associated with aging", " The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers ( VDPP ) brought together 10 cohorts to conduct a prospect i ve study of the association between vitamin D status , measured as serum concentrations of 25-hydroxyvitamin D ( 25(OH)D ) , and the development of 7 rarer cancer sites : endometrial , esophageal , gastric , kidney , non-Hodgkin lymphoma , ovarian , and pancreatic cancers . The cohorts come from 3 continents , with participants from a wide range of latitude who are racially diverse . Across each cancer site , there was no evidence of a protective association between higher concentrations of 25-hydroxyvitamin D ( > 75 nmol/L ) and cancer outcome . An increased risk at very high levels ( ≥100 nmol/L ) was noted for pancreatic cancer , confirming previous reports . The articles included in this issue detail the overall design and governance of the project , correlates of vitamin D status , and results from the cancer site-specific investigations . The Vitamin D Pooling Project realizes a major goal of consortium efforts , namely , to rigorously test hypotheses for rarer cancer outcomes that may not be adequately addressed in any one prospect i ve cohort study . The results of this study have application for the planning and conduct of intervention trials , especially in determining potential risks", "Estrogen deficiency and declining calcium absorption due to reduced calcitriol levels or intestinal resistance to calcitriol , are important factors in the pathogenesis of age-related bone loss . The main objective of this study was to examine the effect of estrogen and 1,25-dihydroxyvitamin D therapy given individually or in combination on bone loss in elderly women . Four hundred eighty-nine elderly women with normal bone density for their age , aged 65 - 77 yr , were entered into a r and omized double blind , placebo-controlled trial . Women were r and omized to one of four groups : conjugated estrogens ( 0.625 mg , daily ) to women without a uterus ( estrogen replacement therapy ) plus medroxyprogesterone acetate ( 2.5 mg , daily ) to women with a uterus ( hormone replacement therapy ) , calcitriol ( 0.25 microg twice daily ) , a combination of hormone replacement therapy/estrogen replacement therapy plus calcitriol , or placebos for 3 yr . The primary outcome was the change in bone mineral density of the femoral neck and spine . In the intent to treat analysis , hormone therapy ( hormone replacement therapy/estrogen replacement therapy ) produced a mean ( + /-1 SD ) increase in bone mineral density of 2.98 % ( + /-5.45 % ) at the femoral neck ( P total hip and trochanter bone mineral density . Calcitriol increased bone mineral density 0.10 % ( + /- 4.27 % ) at the femoral neck ( P = 0.57 ) and 1.65 % ( + /- 4.83 % ) at the spine ( P of hormone replacement therapy/estrogen replacement therapy + calcitriol increased bone mineral density 3.80 % ( + /-4.95 % ) at the femoral neck ( P hip and trochanter . All three treatment groups differed significantly from placebo at the spine and for the hormone replacement therapy/estrogen replacement therapy groups at the femoral neck , spine , total hip and trochanter . There were no significant differences between combination therapy and hormone replacement therapy/estrogen replacement therapy alone on bone mineral density at any site in the intent to treat analysis . In a secondary analysis of the effect in women who were adherent to treatment , calcitriol had a more significant effect on spine ( P = 0.003 ) and total hip ( P = 0.004 ) . The increase in bone mineral density in the adherent groups of women was always higher compared with the intent to treat groups . Combination therapy compared with hormone replacement therapy/estrogen replacement therapy alone produced a significantly greater response in trochanter ( P = 0.007 ) and total hip bone mineral density ( P = 0.0017 ) . In summary , hormone replacement therapy/estrogen replacement therapy alone and in combination with calcitriol therapy was highly effective in reducing bone resorption and increasing bone mineral density at the hip and other clinical ly relevant sites in a group of elderly women , with normal bone density for their age . Calcitriol was effective in increasing spine bone mineral density . In the adherent women , combination therapy with hormone replacement therapy/estrogen replacement therapy and calcitriol increased bone mineral density significantly more in the total hip and trochanter than did hormone replacement therapy/estrogen replacement therapy alone", "CONTEXT Observational studies show an association between low vitamin D status assessed by circulating 25-hydroxyvitamin D and cardiovascular events and mortality . Data from r and omized controlled trials are limited . OBJECTIVE The aim of this study was to test whether daily doses of vitamin D(3 ) at 400 or 1000 IU/d for 1 yr affected conventional markers of cardiovascular disease ( CVD ) risk . DESIGN We conducted a parallel-group , double-blind , placebo-controlled r and omized controlled trial . R and omization was computer generated . Participants and study investigators were blinded to intervention groupings throughout the trial . SETTING The study was conducted at the Clinical Research Facility , University of Aberdeen , United Kingdom . PARTICIPANTS A total of 305 healthy postmenopausal women aged 60 - 70 yr were recruited for the study . INTERVENTION Each woman received a daily capsule of 400 or 1000 IU vitamin D(3 ) or placebo r and omly allocated . MAIN OUTCOME MEASURES Primary outcomes were serum lipid profile [ total , high-density lipoprotein , and low-density lipoprotein cholesterol ; triglycerides ; and apolipoproteins A-1 and B100 ] , insulin resistance ( homeostatic model assessment ) , inflammatory biomarkers ( high-sensitivity C-reactive protein , IL-6 , soluble intracellular adhesion molecule-1 ) , and blood pressure . RESULTS A total of 265 ( 87 % ) participants completed all study visits . Small differences between groups for serum apolipoprotein B100 change [ repeated measures ANOVA , P=0.04 ; mean ( sd ) , -1.0 ( 10.0 ) mg/dl ( 400 IU ) ; -1.0 ( 10.0 ) mg/dl ( 1000 IU ) ; and + 0.02 ( 10.0 ) mg/dl ( placebo ) ] were not considered clinical ly significant . Other systemic markers for CVD risk remained unchanged . There was significant seasonal variation in systolic and diastolic blood pressure independent of vitamin D dose ( P ( sd ) reduction in systolic blood pressure from winter to summer was -6.6 ( 10.8 ) mm Hg . CONCLUSIONS Improving vitamin D status through dietary supplementation is unlikely to reduce CVD risk factors . Confounding of seasonality should be recognized and addressed in future studies of vitamin", "BACKGROUND There is a paucity of research evaluating the relation between vitamin D and recurrence of breast cancer after treatment . OBJECTIVE This study was design ed to evaluate the associations between circulating concentrations of 25-hydroxyvitamin D [ 25(OH)D ] and dietary , supplemental , and total intake of vitamin D and recurrent or new breast cancer events within the Women 's Healthy Eating and Living ( WHEL ) Study . DESIGN A prospect i ve cohort study design ( n = 3085 ) was used to evaluate the relation between dietary , supplemental , and total vitamin D intake and recurrent breast cancer , and a nested case-control study with 512 matched pairs was used for analysis of the association between 25(OH)D and breast cancer recurrence . RESULTS No relation between 25(OH)D and breast cancer recurrence was observed . Compared with women with serum concentrations of 25(OH)D ≥ 30 ng/mL , adjusted odds ratios ( 95 % CI ) for breast cancer recurrence were 1.14 ( 0.57 , 2.31 ) for those with concentrations . Vitamin D intake was not related to breast cancer recurrence overall , although for premenopausal women there was a significant inverse association between dietary vitamin D intake and recurrence ( P for trend = 0.02 ) . CONCLUSION These results do not provide support for a relation between concentrations of 25(OH)D after treatment and the recurrence of breast cancer . This trial is registered at clinical trials.gov for the WHEL Study as NCT00003787", "To evaluate the effects of alfacalcidol on bone turnover in elderly women with osteoporosis , an open-label , prospect i ve , calcium-controlled study was conducted . A total of 80 patients with osteoporosis were divided into two groups : the control group , group C ( mean age , 78.0 years ) , in which patients were given calcium , and group D ( mean age , 77.4 years ) , in which the patients were given alfacalcidol 1 µg/day together with calcium for 6 months . Calcium regulation , lumbar bone mineral density ( LBMD ) , and markers for bone turnover were assessed . A significant increase in urinary calcium/creatinine ratio ( 90 % increase from baseline at 3 months ; P = 0.0083 , and 60 % at 6 months ; P = 0.0091 ) and a significant decrease in serum parathyroid hormone ( 30 % decrease from baseline at 6 months ; P of bone resorption markers ( deoxypyridinoline and N-telopeptide ) at 6 months ( about 15 % decrease from the baseline values ) were observed in group D compared with the corresponding changes in group C. The changes in bone formation markers ( bone-derived alkaline phosphatase and osteocalcin ) in group D were significantly different at 6 months ( −21.5 % ; P = 0.0047 and −13.4 % ; P = 0.0032 , respectively ) from the values in group C. The magnitudes of the decrease in bone turnover markers were highly correlated with the corresponding baseline values , suggesting that alfacalcidol treatment effectively reduces bone turnover in patients with high bone turnover rates . The LBMD in group D increased by 1.7 % and that in group C decreased by 1.6 % ( P = 0.0384 ) . The changes in calcium metabolism and LBMD were in good agreement with those in previous reports . Although the changes in bone turnover markers in group D were slight , significant reduction in bone turnover with alfacalcidol treatment , together with the change in calcium metabolism , may account for the effects of alfacalcidol on BMD and on fracture prevention reported previously . In conclusion , alfacalcidol reduces bone turnover in elderly women with high-bone-turnover osteoporosis , and it may have beneficial effects on bone", "Experimental and epidemiological studies suggest that calcium and vitamin D supplements may lower blood pressure . We examined the effect of calcium plus vitamin D supplementation on blood pressure and the incidence of hypertension in postmenopausal women . The Women 's Health Initiative Calcium/Vitamin D Trial r and omly assigned 36 282 postmenopausal women to receive 1000 mg of elemental calcium plus 400 IU of vitamin D3 daily or placebo in a double-blind fashion . Change in blood pressure and the incidence of hypertension were ascertained . Over a median follow-up time of 7 years , there was no significant difference in the mean change over time in systolic blood pressure ( 0.22 mm Hg ; 95 % CI : −0.05 to 0.49 mm Hg ) and diastolic blood pressure ( 0.11 mm Hg ; 95 % CI : −0.04 to 0.27 mm Hg ) between the active and placebo treatment groups . This None result was robust in analyses accounting for nonadherence to study pills and in baseline subgroups of interest , including black subjects and women with hypertension or high levels of blood pressure , with low intakes of calcium and vitamin D or low serum levels of vitamin D. In 17 122 nonhypertensive participants at baseline , the hazard ratio for incident hypertension associated with calcium/vitamin D treatment was 1.01 ( 95 % CI : 0.96 to 1.06 . ) In postmenopausal women , calcium plus vitamin D3 supplementation did not reduce either blood pressure or the risk of developing hypertension over 7 years of follow-up", "Objective : Coronary artery calcified plaque is a marker for atheromatous plaque burden and predicts future risk of cardiovascular events . The relationship between calcium plus vitamin D ( calcium/D ) supplementation and coronary artery calcium ( CAC ) has not been previously assessed in a r and omized trial setting . We compared CAC scores after trial completion between women r and omized to calcium/vitamin D supplementation and women r and omized to placebo . Methods : In an ancillary sub study of women r and omized to calcium carbonate ( 1,000 mg of elemental calcium daily ) plus vitamin D3 ( 400 IU daily ) or placebo , nested within the Women 's Health Initiative trial of estrogen among women who underwent hysterectomy , we measured CAC with cardiac CT in 754 women aged 50 to 59 years at r and omization . Imaging for CAC was performed at 28 of 40 centers after a mean of 7 years of treatment , and scans were read central ly . CAC scores were measured by a central reading center with masking to r and omization assignments . Results : Posttrial CAC measurements were similar in women r and omized to calcium/D supplementation and those receiving placebo . The mean CAC score was 91.6 for women receiving calcium/D and 100.5 for women receiving placebo ( rank test P value = 0.74 ) . After adjustment for coronary risk factors , multivariate odds ratios for increasing CAC score cutpoints ( CAC > 0 , ≥10 , and ≥100 ) for calcium/D versus placebo were 0.92 ( 95 % CI , 0.64 - 1.34 ) , 1.29 ( 0.88 - 1.87 ) , and 0.90 ( 0.56 - 1.44 ) , respectively . Corresponding odds ratios among women with a 50 % or higher adherence to study pills and for higher levels of CAC ( > 300 ) were similar . Conclusions : Treatment with moderate doses of calcium plus vitamin D3 did not seem to alter coronary artery calcified plaque burden among postmenopausal women . Whether higher or lower doses would affect this outcome remains uncertain", "BACKGROUND Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers . However , interventional studies to test this effect are lacking . OBJECTIVE The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk of all types . DESIGN This was a 4-y , population -based , double-blind , r and omized placebo-controlled trial . The primary outcome was fracture incidence , and the principal secondary outcome was cancer incidence . The subjects were 1179 community-dwelling women r and omly selected from the population of healthy postmenopausal women aged > 55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were r and omly assigned to receive 1400 - 1500 mg supplemental calcium/d alone ( Ca-only ) , supplemental calcium plus 1100 IU vitamin D3/d ( Ca + D ) , or placebo . RESULTS When analyzed by intention to treat , cancer incidence was lower in the Ca + D women than in the placebo control subjects ( P unadjusted relative risks ( RR ) of incident cancer in the Ca + D and Ca-only groups were 0.402 ( P = 0.01 ) and 0.532 ( P = 0.06 ) , respectively . When analysis was confined to cancers diagnosed after the first 12 mo , RR for the Ca + D group fell to 0.232 ( CI : 0.09 , 0.60 ; P treatment and serum 25-hydroxyvitamin D concentrations were significant , independent predictors of cancer risk . CONCLUSIONS Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women . This trial was registered at clinical trials.gov as NCT00352170", "BACKGROUND In a previous 2-y r and omized controlled trial , we showed that calcium- and vitamin D3-fortified milk stopped or slowed bone loss at several clinical ly relevant skeletal sites in older men . OBJECTIVE The present study aim ed to determine whether the skeletal benefits of the fortified milk were sustained after withdrawal of the supplementation . DESIGN One hundred nine men > 50 y old who had completed a 2-y fortified milk trial were followed for an additional 18 mo , during which no fortified milk was provided . Bone mineral density ( BMD ) of the total hip , femoral neck , lumbar spine , and forearm was measured by using dual-energy X-ray absorptiometry . RESULTS Comparison of the mean changes from baseline between the groups ( adjusted for baseline age , BMD , total calcium intake , and change in weight ) showed that the net beneficial effects of fortified milk on femoral neck and ultradistal radius BMD at the end of the intervention ( 1.8 % and 1.5 % , respectively ; P total hip ( 0.8 % ; P = 0.17 ) also persisted at follow-up ( 0.7 % ; P = 0.10 ) , but there were no lasting benefits at the lumbar spine . The average total dietary calcium intake in the milk supplementation group at follow-up approximated recommended amounts for Australian men > 50 y old ( 1000 mg/d ) but did not differ significantly from that in the control subjects ( 1021 versus 890 mg/d ) . CONCLUSION Supplementation with calcium- and vitamin D3-fortified milk for 2 y may provide some sustained benefits for BMD in older men after withdrawal of supplementation", "In all species tested , except humans , biological differences between vitamins D2 and D3 are accepted as fact . To test the presumption of equivalence in humans , we compared the ability of equal molar quantities of vitamin D2 or D3 to increase serum 25-hydroxyvitamin D [ 25(OH)D ] , the measure of vitamin D nutrition . Subjects took 260 nmol ( approximately 4000 IU ) vitamin D2 ( n=17 ) or vitamin D3 ( n=55 ) daily for 14 d. 25(OH)D was assayed with a method that detects both the vitamin D2 and D3 forms . With vitamin D3 , mean ( + /-SD ) serum 25(OH)D increased from 41.3+/-17.7 nmol/L before to 64.6+/-17.2 nmol/L after treatment . With vitamin D2 , the 25(OH)D concentration went from 43.7+/-17.7 nmol/L before to 57.4+/-13.0 nmol/L after . The increase in 25(OH)D with vitamin D3 was 23.3+/-15.7 nmol/L , or 1.7 times the increase obtained with vitamin D2 ( 13.7+/-11.4 nmol/L ; P=0.03 ) . There was an inverse relation between the increase in 25(OH)D and the initial 25(OH)D concentration . The lowest 2 tertiles for basal 25(OH)D showed larger increases in 25(OH)D : 30.6 and 25.5 nmol/L , respectively , for the first and second tertiles . In the highest tertile [ 25(OH)D > 49 nmol/L ] the mean increase in 25(OH)D was 13.3 nmol/L ( P vitamin D3 shown here may seem small , it is more than what others have shown for 25(OH)D increases when comparing 2-fold differences in vitamin D3 dose . The assumption that vitamins D2 and D3 have equal nutritional value is probably wrong and should be reconsidered", "BACKGROUND Epidemiological evidence supports a relationship between vitamin D and mental well-being , although evidence from large-scale placebo-controlled intervention trials is lacking . AIMS To examine if vitamin D supplementation has a beneficial effect on mood in community-dwelling older women ; if a single annual large dose of vitamin D has a role in the prevention of depressive symptoms ; and if there is an association between serum 25-hydroxyvitamin D levels and mental health . METHOD A double-blind , r and omised , placebo-controlled trial of women aged 70 or older ( the Vital D Study : IS RCT N83409867 and ACTR12605000658617 ) . Participants were r and omly assigned to receive 500 000 IU vitamin D(3 ) ( cholecalciferol ) orally or placebo every autumn/winter for 3 - 5 consecutive years . The tools utilised at various time points were the General Health Question naire , the 12-item Short Form Health Survey , the Patient Global Impression-Improvement scale and the WHO Well-Being Index . Serum 25-hydroxyvitamin D levels were measured in a subset of 102 participants . RESULTS In this non- clinical population , no significant differences between the vitamin D and placebo groups were detected in any of the measured outcomes of mental health . Serum 25-hydroxyvitamin D levels in the vitamin D group were 41 % higher than the placebo group 12 months following their annual dose . Despite this difference , scores from the question naires did not differ . Furthermore , there was no interaction between those on antidepressant/anxiety medication at baseline and the treatment groups . CONCLUSIONS The lack of improvement in indices of mental well-being in the vitamin D group does not support the hypothesis that an annual high dose of vitamin D(3 ) is a practical intervention to prevent depressive symptoms in older community-dwelling women", "The Women 's Health Initiative ( WHI ) is a large and complex clinical investigation of strategies for the prevention and control of some of the most common causes of morbidity and mortality among postmenopausal women , including cancer , cardiovascular disease , and osteoporotic fractures . The WHI was initiated in 1992 , with a planned completion date of 2007 . Postmenopausal women ranging in age from 50 to 79 are enrolled at one of 40 WHI clinical centers nationwide into either a clinical trial ( CT ) that will include about 64,500 women or an observational study ( OS ) that will include about 100,000 women . The CT is design ed to allow r and omized controlled evaluation of three distinct interventions : a low-fat eating pattern , hypothesized to prevent breast cancer and colorectal cancer and , secondarily , coronary heart disease ; hormone replacement therapy , hypothesized to reduce the risk of coronary heart disease and other cardiovascular diseases and , secondarily , to reduce the risk of hip and other fractures , with increased breast cancer risk as a possible adverse outcome ; and calcium and vitamin D supplementation , hypothesized to prevent hip fractures and , secondarily , other fractures and colorectal cancer . Overall benefit-versus-risk assessment is a central focus in each of the three CT components . Women are screened for participation in one or both of the components -- dietary modification ( DM ) or hormone replacement therapy (HRT)--of the CT , which will r and omize 48,000 and 27,500 women , respectively . Women who prove to be ineligible for , or who are unwilling to enroll in , these CT components are invited to enroll in the OS . At their 1-year anniversary of r and omization , CT women are invited to be further r and omized into the calcium and vitamin D ( CaD ) trial component , which is projected to include 45,000 women . The average follow-up for women in either CT or OS is approximately 9 years . Concerted efforts are made to enroll women of racial and ethnic minority groups , with a target of 20 % of overall enrollment in both the CT and OS . This article gives a brief description of the rationale for the interventions being studied in each of the CT components and for the inclusion of the OS component . Some detail is provided on specific study design choices , including eligibility criteria , recruitment strategy , and sample size , with attention to the partial factorial design of the CT . Some aspects of the CT monitoring approach are also outlined . The scientific and logistic complexity of the WHI implies particular leadership and management challenges . The WHI organization and committee structure employed to respond to these challenges is also briefly described", "BACKGROUND Low 25-hydroxy-vitamin D ( 25(OH)D ) levels are inversely related to blood pressure ( BP ) and have been associated with incident hypertension . In people living at northern latitudes diminished cholecalciferol synthesis in the winter increases the risk of vitamin D deficiency . We wanted to test the hypothesis that daily cholecalciferol supplementation in the winter lowers BP in patients with hypertension . METHODS We investigated the effect of 75 µg ( 3,000 IU ) cholecalciferol per day in a r and omized , placebo-controlled , double-blind study in 130 hypertensive patients residing in Denmark ( 56º N ) . Ambulatory BP ( 24-h BP ) and arterial stiffness were measured before and after 20 weeks of treatment , that took place between October and March . RESULTS A total of 112 patients ( mean age 61 ± 10 ) with a baseline p-25(OH)D of 23 ± 10 ng/ml completed the study . Compared with placebo , a nonsignificant 3/1 mm Hg ( P = 0.26/0.18 ) reduction was found in 24-h BP . In patients with vitamin D insufficiency ( 92 ) , 24-h BP decreased by 4/3 mm Hg ( P = 0.05/0.01 ) . Central BP ( CBP ) estimated by applanation tonometry and calibrated with a st and ardized office BP was reduced by 7/2 mm Hg ( P = 0.007/0.15 ) vs. placebo . No differences in carotid-femoral pulse wave velocity ( PWV ) or central augmentation index ( AIx ) were found between treatment arms . CONCLUSIONS Cholecalciferol supplementation , by a dose that effectively increased vitamin D levels , did not reduce 24-h BP , although central systolic BP decreased significantly . In a post-hoc subgroup analysis of 92 subjects with baseline p-25(OH)D levels decreases in 24-h systolic and diastolic BP occurred during cholecalciferol supplementation ", "In women , the influence of and rogens on bone health is not clear . It has been suggested that the and rogen receptor ( AR ) genotype is associated with bone mineral density and serum and rogen levels in pre- and perimenopausal women , but the association between AR genotype , bone mineral density , and fracture risk has not been studied in postmenopausal women . Therefore , we studied whether AR polymorphism affects bone mineral density , bone mineral density change , or fracture risk in a 5-year r and omized hormone replacement therapy ( HRT ) trial on 331 early postmenopausal women ( mean baseline age , 52.7 + /- 2.3 years ) . The participants consisted of two treatment groups : the HRT group ( n = 151 ) received a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate with or without vitamin D3 , 100 - 300 IU + 93 mg calcium as lactate/day , and the non-HRT group ( n = 180 ) received 93 mg calcium alone or in combination with vitamin D3 , 100 - 300 IU/day for 5 years . Bone mineral density was measured from lumbar spine and proximal femur ( DXA ) before and after the 5-year trial . All new symptomatic , radiographically defined fractures were recorded during the follow-up . The length of CAG repeat in exon 1 of AR gene was evaluated after polymerase chain reaction ( PCR ) amplification . The subjects were divided into three repeat groups according to AR alleles . None of the baseline characteristics were associated with AR gene polymorphism and HRT treatment . The polymorphism did not influence the calculated annual changes of lumbar or femoral neck bone mineral density during the 5-year follow-up in the HRT ( p = 0.926 and 0.146 , respectively ) or non-HRT ( p = 0.818 and 0.917 , respectively ) groups . In all , 28 women sustained 33 fractures during the follow-up . Thus , the numbers of fractures were limited . The AR repeat length variation was not significantly associated with fracture risk in the HRT or non-HRT groups ( p = 0.632 and 0.459 , respectively ; Cox proportional hazards model ) . In conclusion , AR gene polymorphism was not associated with baseline bone mineral density , 5-year bone mineral density change , or fracture risk in early postmenopausal Finnish women", "The exact antineoplastic effects of calcium and vitamin D3 in the human colon are unclear . Animal and in vitro studies show that these two agents reduce oxidative stress ; however , these findings have never been investigated in humans . To address this , we conducted a pilot , r and omized , double-blind , placebo-controlled , 2 × 2 factorial clinical trial to test the effects of calcium and vitamin D3 on a marker of oxidative DNA damage , 8-hydroxy-2′-deoxyguanosine ( 8-OH-dG ) , in the normal colorectal mucosa . Patients ( N = 92 ) with at least one pathology-confirmed colorectal adenoma were treated with 2 g/d calcium and /or 800 IU/d vitamin D3 versus placebo over 6 months . Overall labeling and colorectal crypt distribution of 8-OH-dG in biopsies of normal-appearing rectal mucosa were detected by st and ardized automated immunohistochemistry and quantified by image analysis . After 6 months of treatment , 8-OH-dG labeling along the full lengths of colorectal crypts decreased by 22 % ( P = 0.15 ) and 25 % ( P = 0.10 ) in the calcium and vitamin D3 groups , respectively , but not in the calcium plus vitamin D3 group . The estimated treatment effects were strongest among participants with higher baseline colon crypt vitamin D receptor expression ( P = 0.05 ) . Overall , these preliminary results indicate that calcium and vitamin D3 may decrease oxidative DNA damage in the normal human colorectal mucosa , support the hypothesis that 8-OH-dG labeling in colorectal crypts is a treatable oxidative DNA damage biomarker of risk for colorectal neoplasms , and provide support for further investigation of calcium and vitamin D3 as chemopreventive agents against colorectal neoplasms . Cancer Epidemiol Biomarkers Prev ; 19(1 ) ;", "Summary Treatment of vitamin D deficiency for 3 months with oral cholecalciferol 5,000 IU daily was more effective than 2,000 IU daily in achieving optimal serum 25-hydroxyvitamin D ( 25OHD ) concentrations . Optimal 25OHD serum level calculated to be 63.8 nmol/L. All parameters of muscle strength improved following administration of cholecalciferol for 3 months . Introduction The aim of this study was to determine the optimal dose of cholecalciferol required to achieve target serum 25OHD level ≥75 nmol/L and its relationship to both bone turnover and muscle strength . Methods Thirty deficient patients ( serum 25OHD ≤50 nmol/L ) were r and omly assigned into two groups — i.e . 2,000 and 5,000 IU/day . Data were collected at baseline , at 2 and 3 months post-therapy : ( a ) clinical demographics , ( b ) dietary calcium recall , ( c ) physical tests of muscle function and ( d ) biochemistry . Statistical analysis used paired student t test and analysis of variance . Regression analysis was used to determine relationship between serum 25OHD and parathyroid hormone ( PTH ) . Results Twenty-six ( 87 % ) patients completed 3 months of therapy . The percent increase in serum 25OHD ( compared to baseline ) was 82.7 % in 2,000-IU group and 219.5 % in 5,000-IU group . All participants ( 100 % ) achieved a serum 25OHD concentration > 50 nmol/L ; only 5 subjects ( 45.4 % ) in 2,000-IU group compared to 14 subjects ( 93.3 % ) in 5,000-IU group achieved final 25OHD concentration ≥75 nmol/L ( p the PTH level increased above the normal range was calculated to be 63.8 nmol/L 25OHD . All parameters of muscle strength showed trends in improvements following the administration of both the 2,000 and 5,000 IU doses . No patient reported untoward side effects and no patient developed hypercalcaemia . Conclusion Treatment for 3 months with oral cholecalciferol 5,000 IU daily may be more effective than 2,000 IU daily in achieving optimal serum 25OHD concentrations in vitamin D-deficient patients", "BACKGROUND Ergocalciferol ( vitamin D(2 ) ) supplementation plays a role in fall prevention , but the effect in patients living in the community in sunny climates remains uncertain . We evaluated the effect of ergocalciferol and calcium citrate supplementation compared with calcium alone on the risk of falls in older women at high risk of falling . METHODS A 1-year population -based , double-blind , r and omized controlled trial of 302 community-dwelling ambulant older women aged 70 to 90 years living in Perth , Australia ( latitude , 32 degrees S ) , with a serum 25-hydroxyvitamin D concentration of less than 24.0 ng/mL and a history of falling in the previous year . Participants were r and omized to receive ergocalciferol , 1000 IU/d , or identical placebo ( hereinafter , ergocalciferol and control groups , respectively ) . Both groups received calcium citrate , 1000 mg/d . Fall data were collected every 6 weeks . RESULTS Ergocalciferol therapy reduced the risk of having at least 1 fall over 1 year after adjustment for baseline height , which was significantly different between the 2 groups ( ergocalciferol group , 53.0 % ; control group , 62.9 % ; odds ratio [ OR ] , 0.61 ; 95 % confidence interval [ CI ] , 0.37 - 0.99 ) . When those who fell were grouped by the season of first fall or the number of falls they had , ergocalciferol treatment reduced the risk of having the first fall in winter and spring ( ergocalciferol group , 25.2 % ; control group , 35.8 % ; OR , 0.55 ; 95 % CI , 0.32 - 0.96 ) but not in summer and autumn , and reduced the risk of having 1 fall ( ergocalciferol group , 21.2 % ; control group , 33.8 % ; OR , 0.50 ; 95 % CI , 0.28 - 0.88 ) but not multiple falls . CONCLUSION Patients with a history of falling and vitamin D insufficiency living in sunny climates benefit from ergocalciferol supplementation in addition to calcium , which is associated with a 19 % reduction in the relative risk of falling , mostly in winter", "Public health recommendations do not distinguish between vitamin D2 and vitamin D3 , yet disagreement exists on whether these two forms should be considered equivalent . The objective of the present study was to evaluate the effect of a daily physiological dose of vitamin D2 or vitamin D3 on 25-hydroxyvitamin D ( 25(OH)D ) status over the winter months in healthy adults living in Dunedin , New Zeal and ( latitude 46 ° S ) . Participants aged 18 - 50 years were r and omly assigned to 25 μg ( 1000 IU ) vitamin D3 ( n 32 ) , 25 μg ( 1000 IU ) vitamin D2 ( n 31 ) or placebo ( n 32 ) daily for 25 weeks beginning at the end of summer . A per- protocol approach , which included ≥ 90 % supplement compliance , was used for all analyses . Serum 25-hydroxyvitamin D3 ( 25(OH)D3 ) , 25-hydroxyvitamin D2 ( 25(OH)D2 ) and parathyroid hormone ( PTH ) were measured at baseline and at 4 , 8 , 13 and 25 weeks . Geometric mean total serum 25(OH)D concentrations ( sum of 25(OH)D2 and 25(OH)D3 ) at baseline was 80 nmol/l . After 25 weeks , participants r and omised to D2 and placebo had a significant reduction in serum 25(OH)D3 concentrations over the winter months compared with vitamin D3-supplemented participants ( both P Supplementation with vitamin D2 increased serum 25(OH)D2 but produced a 9 ( 95 % CI 1 , 17 ) nmol/l greater decline in the 25(OH)D3 metabolite compared with placebo ( P 0.036 ) . Overall , total serum 25(OH)D concentrations were 21 ( 95 % CI 14 , 30 ) nmol/l lower in participants receiving vitamin D2 compared with those receiving D3 ( P whom total serum 25(OH)D concentrations remained unchanged . No intervention-related changes in PTH were observed . Daily supplementation of vitamin D3 was more effective than D2 ; however , the functional consequence of the differing metabolic response warrants further investigation", "BACKGROUND Although some observational studies have associated higher calcium intake and especially higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk , no r and omized trial has evaluated these relationships . METHODS Postmenopausal women ( N = 36 282 ) who were enrolled in a Women 's Health Initiative clinical trial were r and omly assigned to 1000 mg of elemental calcium with 400 IU of vitamin D(3 ) daily or placebo for a mean of 7.0 years to determine the effects of supplement use on incidence of hip fracture . Mammograms and breast exams were serially conducted . Invasive breast cancer was a secondary outcome . Baseline serum 25-hydroxyvitamin D levels were assessed in a nested case-control study of 1067 case patients and 1067 control subjects . A Cox proportional hazards model was used to estimate the risk of breast cancer associated with r and om assignment to calcium with vitamin D(3 ) . Associations between 25-hydroxyvitamin D serum levels and total vitamin D intake , body mass index ( BMI ) , recreational physical activity , and breast cancer risks were evaluated using logistic regression models . Statistical tests were two-sided . RESULTS Invasive breast cancer incidence was similar in the two groups ( 528 supplement vs 546 placebo ; hazard ratio = 0.96 ; 95 % confidence interval = 0.85 to 1.09 ) . In the nested case-control study , no effect of supplement group assignment on breast cancer risk was seen . Baseline 25-hydroxyvitamin D levels were modestly correlated with total vitamin D intake ( diet and supplements ) ( r = 0.19 , P Baseline 25-hydroxyvitamin D levels were not associated with breast cancer risk in analyses that were adjusted for BMI and physical activity ( P(trend ) = .20 ) . CONCLUSIONS Calcium and vitamin D supplementation did not reduce invasive breast cancer incidence in postmenopausal women . In addition , 25-hydroxyvitamin D levels were not associated with subsequent breast cancer risk . These findings do not support a relationship between total vitamin D intake and 25-hydroxyvitamin D levels with breast cancer risk", "Data Safety Monitoring Committees ( DSMB ) for large , long-term r and omized trials of agents in common use face challenging problems especially when the emerging data indicate unanticipated effects . The DSMB for the Women 's Health Initiative Clinical Trials , on observing early indication of a surprising adverse cardiovascular effect of post-menopausal hormones , spent several years deliberating what recommendations it should make . This paper describes the dilemmas faced by the DSMB and the considerations it made over the course of its existence . The paper concludes with some recommendations for other DSMBs", "BACKGROUND Some evidence suggests that vitamin D may reduce breast cancer risk . Despite the biological interaction between vitamin D and calcium , few studies have evaluated their joint effects on breast cancer risk . OBJECTIVE The objective was to evaluate the associations and potential interaction between vitamin D and calcium ( from food and supplements ) and breast cancer risk in a population -based case-control study . DESIGN Breast cancer cases aged 25 - 74 y ( diagnosed 2002 - 2003 ) were identified through the Ontario Cancer Registry . Controls were identified by using r and om digit dialing ; 3101 cases and 3471 controls completed epidemiologic and food-frequency question naires . Adjusted odds ratios ( ORs ) and 95 % CIs were estimated by using multivariate logistic regression . RESULTS Vitamin D and calcium intakes from food only and total combined intakes ( food and supplements ) were not associated with breast cancer risk , although the mean intake of vitamin D was low . Vitamin D supplement intake > 10 microg/d ( 400 IU/d ) compared with no intake was associated with a reduced risk of breast cancer ( adjusted OR : 0.76 ; 95 % CI : 0.59 , 0.98 ) . No categories of calcium supplement intake were significantly associated with reduced breast cancer risk , but a significant inverse trend was observed ( P = 0.04 ) . There were no significant interactions involving vitamin D , calcium , or menopausal status . CONCLUSIONS No associations were found between overall vitamin D or calcium intake and breast cancer risk . Vitamin D from supplements was independently associated with reduced breast cancer risk . Further research is needed to investigate the effects of higher doses of vitamin D and calcium supplements", "In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias", "Sun exposure is associated with lower death rates for pancreatic cancer in some ecological studies . Skin exposure to UVB light induces cutaneous production of precursors to 25-hydroxyvitamin D [ 25(OH)D ] . Pancreatic islet and duct cells express 25(OH)D(3)-1alpha-hydroxylase that generates the biologically active 1,25(OH)(2 ) vitamin D form . Thus , 25(OH)D concentrations could affect pancreatic function and possibly pancreatic cancer etiology . We conducted a prospect i ve nested case-control study in the Alpha-Tocopherol , Beta-Carotene Cancer Prevention cohort of male Finnish smokers , ages 50 to 69 years at baseline , to test whether more adequate vitamin D status , as determined by prediagnostic serum 25(OH)D concentrations , was associated with lower pancreatic cancer risk . Two hundred incident exocrine pancreatic cancer cases that occurred between 1985 and 2001 ( up to 16.7 years of follow-up ) were matched by age and date of blood draw to 400 controls who were alive and free of cancer at the time the case was diagnosed . Odds ratios ( OR ) and 95 % confidence intervals ( 95 % CI ) were calculated using conditional logistic regression . Higher vitamin D concentrations were associated with a 3-fold increased risk for pancreatic cancer ( highest versus lowest quintile , > 65.5 versus pancreatic cancer risk compared with those with lower status . Our findings need to be replicated in other population s and caution is warranted in their interpretation and implication . Our results are intriguing and may provide clues that further the underst and ing of the etiology of this highly fatal cancer", "Vitamin D deficiency in the patients treated for breast cancer is associated with numerous adverse effects ( bone loss , arthralgia , and falls ) . The first aim of this study was to assess vitamin D status , determined by 25-OH vitamin D levels , among women diagnosed with breast cancer according to demographic/ clinical variables and bone mineral density ( BMD ) . The second aim of this study was to evaluate the effect of daily low-dose and weekly high-dose vitamin D supplementation on 25-OH vitamin D levels . This retrospective study included 224 women diagnosed with stage 0–III breast cancer who received treatment at the James P. Wilmot Cancer Center at the University of Rochester Medical Center . Total 25-OH vitamin D levels ( D2 + D3 ) were determined at baseline for all participants . Vitamin D deficiency was defined as a 25-OH vitamin D level . BMD was assessed during the period between 3 months before and 6 months following the baseline vitamin D assessment . Based on the participants ’ baseline levels , they received either no supplementation , low-dose supplementation ( 1,000 IU/day ) , or high-dose supplementation ( ≥50,000 IU/week ) , and 25-OH vitamin D was reassessed in the following 8–16 weeks . Approximately 66.5 % had deficient/insufficient vitamin D levels at baseline . Deficiency/insufficiency was more common among non-Caucasians , women with later-stage disease , and those who had previously received radiation therapy ( P Breast cancer patients with deficient/insufficient 25-OH vitamin D levels had significantly lower lumbar BMD ( P = 0.03 ) . Compared to the no-supplementation group , weekly high-dose supplementation significantly increased 25-OH vitamin D levels , while daily low-dose supplementation did not significantly increase levels . Vitamin D deficiency and insufficiency were common among women with breast cancer and associated with reduced BMD in the spine . Clinicians should carefully consider vitamin D supplementation regimens when treating vitamin D deficiency/insufficiency in breast cancer patients", "Genetic factors regulate bone mineral density ( BMD ) and possibly development of osteoporosis . It has been suggested that estrogen receptor alpha ( ERalpha ) genotype is associated with BMD , but the association between ERalpha genotype , fracture risk , and postmenopausal hormone replacement therapy ( HRT ) has not been studied . Therefore , we evaluated whether ERalpha polymorphism is associated with fracture risk in a 5-year trial with HRT in a population -based , r and omized group of 331 early postmenopausal women . The participants consisted of two treatment groups : the HRT group ( n = 151 ) received a sequential combination of 2 mg of estradiol valerate ( E2Val ) and 1 mg of cyproterone acetate with or without vitamin D3 , 100 - 300 IU + 93 mg calcium as lactate per day ; and the non-HRT group ( n = 180 ) received 93 mg of calcium alone or in combination with vitamin D3 , 100 - 300 IU/day . All new symptomatic , radiographically defined fractures were recorded . Pvu II restriction fragment length polymorphism of the ERalpha was determined using polymerase chain reaction ( PCR ) . In all , 28 women sustained 33 fractures during the approximately 5.1-year follow-up . In the HRT group , the ERalpha genotype ( PP , Pp , and pp ) was not significantly associated with fracture risk ( p = 0.138 ; Cox proportional hazards model ) . When the genotype was dichotomized ( PP + Pp vs. pp ) , the incidence of new fractures in the HRT group was significantly reduced in women with the P allele ( p = 0.046 ) with the relative risk ( HR ) of 0.25 ( 95 % CI , 0.07 - 0.98 ) , in comparison with the non-P allele group . After adjustment for time since menopause and previous fracture , the association between the dichotomous genotype and fracture risk persisted with HR of 0.24 ( 95 % CI , 0.06 - 0.95;p = 0.042 ) . In the non-HRT group , the ERalpha genotype was not significantly associated with fracture risk . During HRT , women with the pp genotype have a greater fracture risk than those with the P allele . The results suggest that the pp genotype is a relatively hormone-insensitive genotype , and it appears that women with the P allele may benefit more from the protective effect of HRT on fracture risk than women with the pp genotype", "The study was design ed to examine the effect of hormone replacement therapy ( HRT ) and low-dose vitamin D ( Vit D ) supplementation on the prevention of bone loss in non-osteoporotic early postmenopausal women and to determine whether Vit D supplementation can give additional benefit to an already optimized estrogen regimen . The effects of HRT and Vit D on bone mineral density ( BMD ) were studied in postmenopausal women in a 2.5-year r and omized placebo-controlled study . The study population was a subgroup of the Kuopio Osteoporosis Risk Factor and Prevention Study ( OSTPRE ) ( n=13100 ) . A total of 464 early postmenopausal women were r and omized to four groups : ( 1 ) HRT ( a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate ( E2Val/CPA ) ; ( 2 ) vitamin D3 ( cholecalciferol , 300 IU/day ) ; ( 3 ) HRT+Vit D ; and ( 4 ) placebo ( calcium lactate ; 93 mg Ca2+/day ) . Lumbar ( L1–4 ) and femoral neck BMD were determined by dual-energy X-ray absorptiometry before and after 2.5 years of treatment . After 2.5 years , lumbar BMD had increased by 1.8 % in the HRT group ( p HRT+Vit D group ( p=0.002 ) , whereas lumbar BMD had decreased by 3.5 % ( p the Vit D group and by 3.7 % ( p placebo group . The loss of femoral neck BMD was lower in the HRT ( −0.3 % ) and the HRT+Vit D ( −0.9 % ) groups compared with the Vit D ( −2.4 % ) and the placebo groups ( −3.7 % ) . This study confirms the beneficial effect of HRT on BMD . It also shows that low-dose vitamin D supplementation has only a minor effect in the prevention of osteoporosis in non-osteoporotic early postmenopausal women and does not give any benefit additional to that of HRT alone", "CONTEXT Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures ; however , adherence to daily supplementation is typically poor . OBJECTIVE To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture . DESIGN , SETTING , AND PARTICIPANTS A double-blind , placebo-controlled trial of 2256 community-dwelling women , aged 70 years or older , considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were r and omly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years . The study concluded in 2008 . INTERVENTION 500,000 IU of cholecalciferol or placebo . MAIN OUTCOME MEASURES Falls and fractures were ascertained using monthly calendars ; details were confirmed by telephone interview . Fractures were radiologically confirmed . In a sub study , 137 r and omly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels . RESULTS Women in the cholecalciferol ( vitamin D ) group had 171 fractures vs 135 in the placebo group ; 837 women in the vitamin D group fell 2892 times ( rate , 83.4 per 100 person-years ) while 769 women in the placebo group fell 2512 times ( rate , 72.7 per 100 person-years ; incidence rate ratio [ RR ] , 1.15 ; 95 % confidence interval [ CI ] , 1.02 - 1.30 ; P = .03 ) . The incidence RR for fracture in the vitamin D group was 1.26 ( 95 % CI , 1.00 - 1.59 ; P = .047 ) vs the placebo group ( rates per 100 person-years , 4.9 vitamin D vs 3.9 placebo ) . A temporal pattern was observed in a post hoc analysis of falls . The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months ( test for homogeneity ; P = .02 ) . In the sub study , the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3 % of the sub study participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group , 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L , were approximately 90 nmol/L at 3 months , and remained higher than the placebo group 12 months after dosing . CONCLUSION Among older community-dwelling women , annual oral administration of high-dose cholecalciferol result ed in an increased risk of falls and fractures . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000658617 ; is rct n.org Identifier : IS RCT N83409867", "OBJECTIVES Oxidative modification of low-density lipoprotein ( oxLDL ) has been suggested to play an important role in the pathogenesis of atherosclerosis , and autoantibodies against oxLDL have recently found to reflect this process . The antioxidant effect and inhibition of LDL oxidation may be one of the cardioprotective mechanisms of postmenopausal estrogen therapy . METHODS The effects of postmenopausal hormone replacement therapy ( HRT ) on the concentrations of serum lipids and oxLDL autoantibodies were studied in a population -based prospect i ve 1-year study with 64 early postmenopausal women ( mean age 52.2 + /- 0.4 ( S.E.M. ) years ) . The participants were r and omized into two treatment groups : HRT-group : Sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate alone or in combination with vitamin D3 , 300 IU/day + calcium lactate , 500 mg/day ( n = 31 ) and the non-HRT-group : Calcium lactate , 500 mg/day alone or in combination with vitamin D3 , 300 IU/day ( n = 33 ) . The groups were well matched regarding age , body mass index and baseline serum lipid concentrations . RESULTS The serum concentrations of total cholesterol and LDL-cholesterol decreased in the HRT-group ( 4.1 % , P = 0.05 and 6.4 % , P = 0.03 , respectively , paired t-test ) but did not change in the non-HRT-group . No changes in the serum concentrations of HDL-cholesterol or triglycerides were observed . Additionally , no changes in oxLDL autoantibody concentrations were observed in either group . CONCLUSIONS Although 1-year HRT lowered serum total- and LDL-cholesterol levels , it did not influence oxLDL antibody titers . On the basis of the present results we can not question the possibility of there being beneficial effects of HRT on the oxidative modification of LDL . However , this effect is not reflected in the levels of oxLDL autoantibodies", "Calcium plus vitamin D ( CaD ) supplementation has a modest but significant effect on slowing loss of femoral bone mass and reducing risk of hip fractures in adherent postmenopausal women . The goal of this study was to determine if CaD supplementation influences hip structural parameters that are associated with fracture risk . We studied 1,970 postmenopausal women enrolled in the Women ’s Health Initiative r and omized controlled trial of CaD at one of three bone mineral density ( BMD ) clinical centers . Hip structural analysis software measured BMD and strength parameters on DXA scans at three regions : femoral narrow neck , intertrochanter , and shaft . R and om effects models were used to test the average differences in hip BMD and geometry between intervention and placebo . There was greater preservation of hip BMD at the narrow neck with CaD relative to placebo across 6 years of intervention . CaD also altered the underlying cross-sectional geometry at the narrow neck in the direction of greater strength , with small increases in cross-sectional area and section modulus and a decrease in buckling ratio with CaD relative to placebo . While trends at both the intertrochanter and shaft regions were similar to those noted at the narrow neck , no significant intervention effects were evident . There was no significant interaction of CaD and age or baseline calcium levels for hip structural properties . CaD supplementation is associated with modest beneficial effects on hip structural features at the narrow neck , which may explain some of the benefit of CaD in reducing hip fracture risk", "In a 5-yr r and omized prospect i ve study we examined the treatment effect of estrogen replacement therapy/hormone replacement therapy ( ERT/HRT ) , calcitriol , ERT/HRT and calcitriol , or placebo for 3 yr and the effect of discontinuation of therapy for 2 more yr on bone mineral density ( BMD ) , calciotropic hormones , markers of bone remodeling , and calcium absorption in 489 elderly women . The treatment phase of the study was double-blinded . After discontinuing therapy for 2 yr , there was rapid bone loss in all 3 treatment groups , and most of the decrease in BMD occurred in the first year . In the ERT/HRT group , spine BMD increased 5.5 % in yr 3 , decreased 3.2 % in yr 4 , and decreased 0.7 % in yr 5 ; femoral neck BMD increased 3.7 % in yr 3 , decreased 2.5 % in yr 4 , and decreased 0.4 % in yr 5 ; total body BMD increased 2.1 % in yr 3 , decreased 1.4 % in yr 4 , and decreased 0.6 % in yr 5 . In the combination group , spine BMD increased 7.1 % in yr 3 , decreased 4.3 % in yr 4 , and decreased 0.3 % in yr 5 ; femoral neck BMD increased 4.5 % in yr 3 , decreased 3.0 % in yr 4 , and decreased 0.01 % in yr 5 ; total body BMD increased 2.2 % in yr 3 , decreased 1.5 % in yr 4 , and decreased 0.6 % in yr 5 . In the calcitriol group , spine BMD increased 1.8 % in yr 3 , decreased 1.8 % in yr 4 , and showed no change in yr 5 ; femoral neck BMD increased 0.2 % in yr 3 , decreased 0.2 % in yr 4 , and decreased 0.6 % in yr 5 ; total body BMD decreased 0.4 % in yr 3 , decreased 0.6 % in yr 4 , and decreased 0.4 % in yr 5 . Compared with placebo , all treated groups at yr 5 had significantly higher total body BMD ; only the combination group had significantly higher spine BMD ( 3.4 % ; P total hip BMD ( 2.4 % ; P only spine BMD in the combination group was significantly higher ( 2.6 % ; P calcium absorption and the decrease in serum PTH levels in the calcitriol groups were reversed after discontinuation of treatment , and the decrease in bone markers was reversed in the hormone-treated groups . These results suggest that discontinuation of ERT/HRT and /or calcitriol therapy in elderly women leads to a decrease in much of the BMD gained on treatment ; however , in the combination group there was a statistically significant residual effect on spine BMD", "STUDY OBJECTIVE To determine if calcitriol is an effective treatment in postmenopausal osteoporosis . DESIGN Double-blind , r and omized clinical trial of 2 years ' duration . SETTING University medical center with patients recruited by media announcements . PATIENTS Eighty-six postmenopausal women with vertebral compression fractures . INTERVENTIONS Patients were treated with calcitriol or placebo . Mean dose was 0.43 micrograms/d . Dietary calcium was 1000 mg/d ( 24.9 mmol/d ) . The medication dose and dietary calcium were adjusted for hypercalciuria or hypercalcemia . MEASUREMENTS AND MAIN RESULTS No significant differences between placebo and control groups were seen in the percent change in total body calcium ( 0.4 % + /- 1.0 compared with 0.0 % + /- 0.9 ) , single photon absorptiometry ( -0.5 % + /- 1.2 compared with -3.1 % + /- 0.9 ) or dual photon absorptiometry ( 0.0 % + /- 1.7 compared with -1.0 % + /- 2.2 ) . New fractures were seen in 16 % of the placebo group and 26 % of the calcitriol groups , so the difference in percent fractures was 10 % ( 95 % CI , -5.7 % to 25.7 % ) . Bone biopsies did not show changes in either group . The calcitriol group had significantly higher serum and urine calcium values , but renal function was not worse than in the placebo group . CONCLUSIONS Calcitriol is not an effective treatment for established postmenopausal osteoporosis", "We prospect ively examined the relation between pretrial serum vitamin D status and risk of oesophageal and gastric cancers among subjects who developed cancer over 5.25 years of follow-up , including 545 oesophageal squamous cell carcinomas ( ESCC ) , 353 gastric cardia adenocarcinomas , 81 gastric noncardia adenocarcinomas , and an age- and sex-stratified r and om sample of 1105 subjects . The distribution of serum 25(OH)D was calculated using the known sampling weights . For the cohort as a whole , the 25th , 50th , and 75th percentile concentrations of 25(OH)-vitamin D were 19.6 , 31.9 , and 48.7 nmol l−1 , respectively , and we found that higher serum 25(OH)D concentrations were associated with monotonically increasing risk of ESCC in men , but not in women . Comparing men in the fourth quartile of serum 25(OH)D concentrations to those in the first , we found a hazard ratio ( HR ) ( 95 % confidence interval ( CI ) ) of 1.77 ( 1.16–2.70 ) , P trend=0.0033 . The same comparison in women had a HR ( 95 % CI ) of 1.06 ( 0.71–1.59 ) , P trend=0.70 . We found no associations for gastric cardia or noncardia adenocarcinoma . Among subjects with low vitamin D status , higher serum 25(OH)D concentrations were associated with significantly increased risk of ESCC in men , but not in women . Further refinements of the analysis did not suggest any factors , which could explain this unexpected result", "BACKGROUND Epidemiological studies have yielded inconsistent associations between vitamin D status and prostate cancer risk , and few studies have evaluated whether the associations vary by disease aggressiveness . We investigated the association between vitamin D status , as determined by serum 25-hydroxyvitamin D [ 25(OH)D ] level , and risk of prostate cancer in a case-control study nested within the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial . METHODS The study included 749 case patients with incident prostate cancer who were diagnosed 1 - 8 years after blood draw and 781 control subjects who were frequency matched by age at cohort entry , time since initial screening , and calendar year of cohort entry . All study participants were selected from the trial screening arm ( which includes annual st and ardized prostate cancer screening ) . Conditional logistic regression was used to estimate adjusted odds ratios ( ORs ) with 95 % confidence intervals ( CIs ) by quintile of season-st and ardized serum 25(OH)D concentration . Statistical tests were two-sided . RESULTS No statistically significant trend in overall prostate cancer risk was observed with increasing season-st and ardized serum 25(OH)D level . However , serum 25(OH)D concentrations greater than the lowest quintile ( Q1 ) were associated with increased risk of aggressive ( Gleason sum > or = 7 or clinical stage III or IV ) disease ( in a model adjusting for matching factors , study center , and history of diabetes , ORs for Q2 vs Q1 = 1.20 , 95 % CI = 0.80 to 1.81 , for Q3 vs Q1 = 1.96 , 95 % CI = 1.34 to 2.87 , for Q4 vs Q1 = 1.61 , 95 % CI = 1.09 to 2.38 , and for Q5 vs Q1 = 1.37 , 95 % CI = 0.92 to 2.05 ; P(trend ) = .05 ) . The rates of aggressive prostate cancer for increasing quintiles of serum 25(OH)D were 406 , 479 , 780 , 633 , and 544 per 100 000 person-years . In exploratory analyses , these associations with aggressive disease were consistent across subgroups defined by age , family history of prostate cancer , diabetes , body mass index , vigorous physical activity , calcium intake , study center , season of blood collection , and assay batch . CONCLUSION The findings of this large prospect i ve study do not support the hypothesis that vitamin D is associated with decreased risk of prostate cancer ; indeed , higher circulating 25(OH)D concentrations may be associated with increased risk of aggressive disease ", "Background — Individuals with vascular or valvular calcification are at increased risk for coronary events , but the relationship between calcium consumption and cardiovascular events is uncertain . We evaluated the risk of coronary and cerebrovascular events in the Women ’s Health Initiative r and omized trial of calcium plus vitamin D supplementation . Methods and Results — We r and omized 36 282 postmenopausal women 50 to 79 years of age at 40 clinical sites to calcium carbonate 500 mg with vitamin D 200 IU twice daily or to placebo . Cardiovascular disease was a prespecified secondary efficacy outcome . During 7 years of follow-up , myocardial infa rct ion or coronary heart disease death was confirmed for 499 women assigned to calcium/vitamin D and 475 women assigned to placebo ( hazard ratio , 1.04 ; 95 % confidence interval , 0.92 to 1.18 ) . Stroke was confirmed among 362 women assigned to calcium/vitamin D and 377 assigned to placebo ( hazard ratio , 0.95 ; 95 % confidence interval , 0.82 to 1.10 ) . In subgroup analyses , women with higher total calcium intake ( diet plus supplements ) at baseline were not at higher risk for coronary events ( P=0.91 for interaction ) or stroke ( P=0.14 for interaction ) if assigned to active calcium/vitamin D. Conclusions — Calcium/vitamin D supplementation neither increased nor decreased coronary or cerebrovascular risk in generally healthy postmenopausal women over a 7-year use period", "Abstract Objective : To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community . Design : R and omised double blind controlled trial of 100 000 IU oral vitamin D3 ( cholecalciferol ) supplementation or matching placebo every four months over five years . Setting and participants : 2686 people ( 2037 men and 649 women ) aged 65 - 85 years living in the general community , recruited from the British doctors register and a general practice register in Suffolk . Main outcome measures : Fracture incidence and total mortality by cause . Results : After five years 268 men and women had incident fractures , of whom 147 had fractures in common osteoporotic sites ( hip , wrist or forearm , or vertebrae ) . Relative risks in the vitamin D group compared with the placebo group were 0.78 ( 95 % confidence interval 0.61 to 0.99 , P=0.04 ) for any first fracture and 0.67 ( 0.48 to 0.93 , P=0.02 ) for first hip , wrist or forearm , or vertebral fracture . 471 participants died . The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 ( 0.74 to 1.06 , P=0.18 ) . Findings were consistent in men and women and in doctors and the general practice population . Conclusion : Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community . What is already known in this topic Vitamin D and calcium supplements are effective in preventing fractures in elderly women Whether isolated vitamin D supplementation prevents fractures is not clear What this paper adds Four monthly oral supplementation with 100 000 IU vitamin D reduces fractures in men and women aged over 65 living in the general community Total fracture incidence was reduced by 22 % and fractures in major osteoporotic sites by 33", "Background R and omised , placebo-controlled trials are needed to provide evidence demonstrating safe , effective interventions that reduce falls and fractures in the elderly . The quality of a clinical trial is dependent on successful recruitment of the target participant group . This paper documents the successes and failures of recruiting over 2,000 women aged at least 70 years and at higher risk of falls or fractures onto a placebo-controlled trial of six years duration . The characteristics of study participants at baseline are also described for this study . Methods The Vital D Study recruited older women identified at high risk of fracture through the use of an eligibility algorithm , adapted from identified risk factors for hip fracture . Participants were r and omised to orally receive either 500,000 IU vitamin D3 ( cholecalciferol ) or placebo every autumn for five consecutive years . A variety of recruitment strategies were employed to attract potential participants . Results Of the 2,317 participants r and omised onto the study , 74 % ( n = 1716/2317 ) were consented onto the study in the last five months of recruiting . This was largely due to the success of a targeted mail-out . Prior to this only 541 women were consented in the 18 months of recruiting . A total of 70 % of all participants were recruited as a result of targeted mail-out . The response rate from the letters increased from 2 to 7 % following revision of the material by a public relations company . Participant demographic or risk factor profile did not differ between those recruited by targeted mail-outs compared with other methods . Conclusion The most successful recruitment strategy was the targeted mail-out and the response rate was no higher in the local region where the study had extensive exposure through other recruiting strategies . The strategies that were labour-intensive and did not result in successful recruitment include the activities directed towards the GP medical centres . Comprehensive recruitment programs employ overlapping strategies simultaneously with ongoing assessment of recruitment rates . In our experience , and others direct mail-outs work best although rights to privacy must be respected . Trial registration IS RCT N83409867 and ACTR12605000658617", "OBJECTIVE The positive short-term effects of postmenopausal hormone replacement therapy ( HRT ) on serum lipids are well known , but it has been suggested that they vanish with time . Cholecalciferol ( vitamin D3 ) is widely used to prevent postmenopausal osteoporosis but the influence of vitamin D3 on serum lipids is poorly known . The long-term effects of HRT and vitamin D3 on the concentrations of serum lipids were studied in a population -based prospect i ve 3-year study . DESIGN AND METHODS 464 women were r and omized into four treatment groups : ( i ) HRT ( sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate ) , ( ii ) Vit D3 ( vitamin D3 300 IU/day ) , ( iii ) HRT+Vit D3 ( both as above ) , ( iv ) placebo ( calcium lactate 500 mg/day ) . RESULTS 320 women completed the study . After three years of treatment , serum concentrations of low density lipoprotein ( LDL ) cholesterol decreased in the HRT group ( 10.1 % , P HRT+Vit D3 group ( 5.9 % , P=0.005 ) , increased in the Vit D3 group ( 4.1 % , P=0.035 ) but remained unchanged in the placebo group . The concentrations of total cholesterol decreased by 5.8 % in the HRT group ( P HRT+Vit D3 group ( P=0.023 ) , but did not change in the other two groups . Serum concentrations of high density lipoprotein ( HDL ) cholesterol decreased in the Vit D3 group ( 5.2 % , P=0.001 ) , HRT+Vit D3 group ( 3.7 % , P=0.046 ) , and the placebo group ( 4.5 % , P=0.006 ) but did not change significantly in the HRT group . The HDL/LDL ratio increased in the HRT group ( 10.5 % , P=0.006 ) and decreased in the Vit D3 group ( 10.5 % , P serum triglycerides increased similarly in all groups ( 14.0 - 18.8 % , P HRT with sequential estradiol valerate and cyproterone acetate on serum lipid concentrations . In addition , the results suggest that vitamin D3 supplementation may have unfavorable effects on lipids in postmenopausal women . Pure vitamin D3 treatment was associated with increased serum LDL cholesterol . Furthermore , the beneficial effects of HRT on serum LDL cholesterol content were reduced when estradiol valerate was combined with vitamin D3 . However , the relevance of these associations to cardiovascular morbidity remains to be established", "Abstract : Hormone replacement therapy ( HRT ) prevents postmenopausal bone loss and fractures . However , the occurrence of women with no bone response to HRT has not been widely examined . We identified the densitometric nonresponders to long-term HRT and investigated some characteristics and biochemical variables as possible predictors of densitometric nonresponse in postmenopausal women . The study population was a sub sample of the Kuopio Osteoporosis Study ( n= 14.220 ) . A total of 464 early postmenopausal women were r and omized into four treatment groups : ( 1 ) HRT ( sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate ) ; ( 2 ) vitamin D3 ; ( 3 ) HRT + Vitamin D3 combined ; and ( 4 ) placebo . In this study , the data from HRT and placebo groups were analyzed . Lumbar ( L2–4 ) and femoral neck bone mineral density ( BMD ) were determined by dual-energy X-ray absorptiometry ( DXA ) at baseline and after 5 years of treatment . A densitometric nonresponder was defined as a woman whose 5-year BMD change was similar to the mean BMD change ( + 95 % CI ) of the placebo group or worse . Altogether , 74 women in the HRT group and 104 women in the placebo group complied with the treatment . According to spinal BMD analysis , 11 % of the women were classified as densitometric nonresponders ; the corresponding proportion for femoral BMD analysis was 26 % . Both smoking ( p= 0.003 ) and low body weight ( p= 0.028 ) were significant risk factors for densitometric nonresponse to HRT . After 6 months of treatment the densitometric nonresponders ( hip ) had a significantly higher mean serum follicle stimulating hormone ( FSH ) level ( p= 0.038 ) and lower increases in serum estradiol levels ( p= 0.006 ) than the densitometric responders . The mean changes in serum FSH and alkaline phosphatase levels were significantly lower among the densitometric nonresponders ( spine ) than responders ( p= 0.043 and 0.017 , respectively ) . In conclusion , this prospect i ve study shows that especially current smokers and women with low body weight are at increased risk of poor bone response to HRT . Repeated serum FSH , estradiol and alkaline phosphatase measurements during the first months of long-term HRT may be helpful in identifying the women with no bone response to HRT", "UNLABELLED Dietary supplementation with vitamin K(1 ) , with vitamin D(3 ) and calcium or their combination , was examined in healthy older women during a 2-year , double-blind , placebo-controlled trial . Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius . INTRODUCTION The putative beneficial role of high dietary vitamin K(1 ) ( phylloquinone ) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind , placebo-controlled trial in healthy Scottish women > or = 60 years of age . MATERIAL S AND METHODS Healthy , nonosteoporotic women ( n = 244 ) were r and omized to receive either ( 1 ) placebo , ( 2 ) 200 microg/day vitamin K(1 ) , ( 3 ) 10 microg ( 400 IU ) vitamin D(3 ) plus 1000 mg calcium/day , or ( 4 ) combined vitamins K(1 ) and D(3 ) plus calcium . Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist , markers of bone turnover , and vitamin status . Supplementation effects were tested using multivariate general linear modeling , with full adjustment for baseline and potential confounding variables . RESULTS Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups . However , women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius . Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years , serum vitamin K(1 ) increased by 157 % ( p percentage of undercarboxylated osteocalcin ( % GluOC ) decreased by 51 % ( p serum 25-hydroxyvitamin D [ 25(OH)D ] increased by 17 % ( p PTH decreased by 11 % ( p = 0.049 ) . CONCLUSIONS These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K(1 ) together with supplements of calcium plus moderate vitamin D(3 ) to enhance BMC at the ultradistal radius , a site consisting of principally trabecular bone . The substantial increase in gamma-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation", "UNLABELLED In this 2-year r and omized controlled study of 167 men > 50 years of age , supplementation with calcium-vitamin D3-fortified milk providing an additional 1000 mg of calcium and 800 IU of vitamin D3 per day was effective for suppressing PTH and stopping or slowing bone loss at several clinical ly important skeletal sites at risk for fracture . INTRODUCTION Low dietary calcium and inadequate vitamin D stores have long been implicated in age-related bone loss and osteoporosis . The aim of this study was to assess the effects of calcium and vitamin D3 fortified milk on BMD in community living men > 50 years of age . MATERIAL S AND METHODS This was a 2-year r and omized controlled study in which 167 men ( mean age + /- SD , 61.9 + /- 7.7 years ) were assigned to receive either 400 ml/day of reduced fat ( approximately 1 % ) ultra-high temperature ( UHT ) milk containing 1000 mg of calcium plus 800 IU of vitamin D3 or to a control group receiving no additional milk . Primary endpoints were changes in BMD , serum 25(OH)D , and PTH . RESULTS One hundred forty-nine men completed the study . Baseline characteristics between the groups were not different ; mean dietary calcium and serum 25(OH)D levels were 941 + /- 387 mg/day and 77 + /- 23 nM , respectively . After 2 years , the mean percent change in BMD was 0.9 - 1.6 % less in the milk supplementation compared with control group at the femoral neck , total hip , and ultradistal radius ( range , p lumbar spine BMD in the milk supplementation group after 12 and 18 months ( 0.8 - 1.0 % , p Serum 25(OH)D increased and PTH decreased in the milk supplementation relative to control group after the first year ( 31 % and -18 % , respectively ; both p Body weight remained unchanged in both groups at the completion of the study . CONCLUSIONS Supplementing the diet of men > 50 years of age with reduced-fat calcium- and vitamin D3-enriched milk may represent a simple , nutritionally sound and cost-effective strategy to reduce age-related bone loss at several skeletal sites at risk for fracture in the elderly", "BACKGROUND Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials . However , r and omized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking . METHODS We conducted a r and omized , double-blind , placebo-controlled trial involving 36,282 postmenopausal women from 40 Women 's Health Initiative centers : 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [ corrected ] twice daily ( 1000 mg of elemental calcium and 400 IU of vitamin D3 ) and 18,106 received a matching placebo for an average of 7.0 years . The incidence of pathologically confirmed colorectal cancer was the design ated secondary outcome . Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study . RESULTS The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo ( 168 and 154 cases ; hazard ratio , 1.08 ; 95 percent confidence interval , 0.86 to 1.34 ; P=0.51 ) , and the tumor characteristics were similar in the two groups . The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups . There were no significant treatment interactions with baseline characteristics . CONCLUSIONS Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women . The long latency associated with the development of colorectal cancer , along with the seven-year duration of the trial , may have contributed to this None finding . Ongoing follow-up will assess the longer-term effect of this intervention . ( Clinical Trials.gov number , NCT00000611 . )", "Background and aims : Insufficient vitamin D status , commonly found in older people , has been associated with muscle weakness which , in old age , impairs mobility and is a risk factor for falling . In a r and omized , double-blind placebo-controlled trial , we tested the hypothesis that vitamin D + calcium supplementation improves muscle strength and mobility , compared with calcium mono-therapy in vitamin D-insufficient female geriatric patients . Methods : Seventy female geriatric patients > 65 years of age with serum 25-hydroxyvitamin D3 ( 25OHD ) concentrations between 20 and 50 nmol/L , visiting an outpatient geriatric department , were included . Participants received either cholecalciferol 400 IU/day + calcium 500 mg/day ( D/Cal group ) or a placebo + calcium 500 mg/day ( Plac/Cal group ) for 6 months . At baseline and 6 months , muscle strength , power and functional mobility were tested . Results : At baseline , 25OHD was significantly ( p with knee extension strength ( r=0.42 ) , h and grip strength ( r=0.28 ) , leg extension power ( r=0.34 ) , Timed Get Up and Go ( r=−0.31 ) and Modified Cooper test ( r=0.44 ) . At 6 months , a significant difference in 25OHD ( 77.2 vs 41.6 nmol/L , p and 1,25OHD was found between the two groups . Significantly improving vitamin D status in the D/Cal group compared with the Plac/Cal group did not result in a significant difference in strength or functional mobility between the two groups . Conclusions : Daily 400IU vitamin D + 500 mg calcium supplementation is not enough to significantly improve strength or mobility in vitamin D-insufficient female geriatric patients", "Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful .", "Pre clinical data indicate that there is substantial antitumor activity and synergy between calcitriol and dexamethasone . On the basis of these data , the authors conducted a phase 2 trial of intravenous ( iv ) calcitriol at a dose of 74 μg weekly ( based on a recent phase 1 trial ) and dexamethasone in patients with castration‐resistant prostate cancer ( CRPC )", "The effects of postmenopausal hormone replacement therapy ( HRT ) and vitamin D on the serum concentrations of three bone biochemical markers and their associations with bone mineral density ( BMD ) were studied in a population -based 1-yr follow-up study . A total of 72 healthy postmenopausal women were r and omized into 4 treatment groups : HRT group ( sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate ) , D group ( vitamin D3 , 300 IU/day ) , HRT+D group ( both of the above ) , and placebo group ( calcium lactate , 500 mg/day ) . Serum concentrations of osteocalcin ( OC ) and bone-specific alkaline phosphatase ( BAP ) were measured as biochemical markers of bone formation , and serum type I collagen carboxy-terminal telopeptide was measured as a marker of bone resorption at baseline and after 6 and 12 months of treatment . To investigate the associations of these markers with BMD , lumbar ( L2-L4 ) and femoral neck BMDs were determined by dual x-ray absorptiometry at baseline and after 2.5 yr of treatment . In both hormone groups , the serum concentrations of the three bone metabolic markers had decreased after 12 months . Those of OC decreased by 29.2 % ( P = 0.017 ) in the HRT group and by 37.3 % ( P = 0.004 ) in the HRT+D group , and BAP concentrations decreased by 34.4 % ( P HRT group and by 36.2 % ( P HRT+D group . Serum type I collagen carboxy-terminal telopeptide concentrations had decreased by 21.6 % ( P = 0.012 ) in HRT group and by 14.1 % ( P = 0.011 ) in the HRT+D group . In the D group , the serum concentrations of BAP had decreased by 11.7 % ( P = 0.040 ) after 12 months , but the other two markers showed no change . The only change seen in the placebo group was a 19.2 % increase in OC concentrations ( P = 0.041 ) after 6 months , but at 12 months , the mean OC level was similar to that at baseline . After 2.5 yr , both lumbar and femoral BMD had decreased in the D group [ 2.1 % ( P = 0.022 ) and 3.6 % ( P = 0.019 ) , respectively ] and in the placebo group [ 3.3 % ( P = 0.009 ) and 2.7 % ( P = 0.010 ) , respectively ] , whereas no significant changes occurred in the hormone groups . There were significant inverse correlations between the changes in lumbar and femoral BMDs and changes in all three biochemical markers ( r = -0.240 through -0.336 ; P = 0.005 - 0.064 ) . Our results suggest that HRT counteracts the biochemical changes caused by increased bone turnover associated with menopause . Importantly , the changes in bone markers correlate with long term changes in BMDs of lumbar spine and femoral neck . Low dose vitamin D treatment , however , seems to have only marginal effects on bone metabolism in early postmenopausal healthy women", "Objective : The aim of this study was to examine the effect of conjugated equine estrogens alone ( ET ) , conjugated equine estrogens + medroxyprogesterone ( EPT ) , calcitriol alone , calcitriol + EPT/ET , or placebo on serum lipid profile and analyze the interaction with estrogen receptor-&agr ; gene single nucleotide polymorphisms ( ESR-&agr ; SNPs ) on the response to therapy . Methods : A total of 489 postmenopausal women older than 65 years were enrolled into a 3-year double-blind , placebo-controlled clinical trial . Results : In both intent-to-treat and complier ( > 80 % adherent ) analysis , there was a significant increase in serum high-density lipoproteins and a significant decrease in serum low-density lipoproteins ( LDLs ) and the LDL/high-density lipoprotein ratio in all hormone treatment groups compared with placebo ( P serum triglycerides and very low-density lipoproteins increased in the EPT and ET + calcitriol groups versus placebo ( P treatment . Genotypes containing the p allele showed a significantly greater decrease in serum cholesterol and very low-density lipoprotein than those having the P allele in the ET + calcitriol group ( P serum cholesterol in the hormone therapy + calcitriol group at the end of 3 years versus the X allele , and a greater decrease in serum LDL in alleles x versus the X in the ET + calcitriol group ( P ET with or without progesterone had a favorable effect on lipid profile in postmenopausal older women , and this was dependent on estrogen receptor SNPs-PvuII and XbaI. However , this interaction with ESR-&agr ; SNPs needs to be confirmed in larger studies", "BACKGROUND The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal . METHODS We recruited 36,282 postmenopausal women , 50 to 79 years of age , who were already enrolled in a Women 's Health Initiative ( WHI ) clinical trial . We r and omly assigned participants to receive 1000 mg of elemental [ corrected ] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo . Fractures were ascertained for an average follow-up period of 7.0 years . Bone density was measured at three WHI centers . RESULTS Hip bone density was 1.06 percent higher in the calcium plus vitamin D group than in the placebo group ( P calcium plus vitamin D supplementation had a hazard ratio of 0.88 for hip fracture ( 95 percent confidence interval , 0.72 to 1.08 ) , 0.90 for clinical spine fracture ( 0.74 to 1.10 ) , and 0.96 for total fractures ( 0.91 to 1.02 ) . The risk of renal calculi increased with calcium plus vitamin D ( hazard ratio , 1.17 ; 95 percent confidence interval , 1.02 to 1.34 ) . Censoring data from women when they ceased to adhere to the study medication reduced the hazard ratio for hip fracture to 0.71 ( 95 percent confidence interval , 0.52 to 0.97 ) . Effects did not vary significantly according to prer and omization serum vitamin D levels . CONCLUSIONS Among healthy postmenopausal women , calcium with vitamin D supplementation result ed in a small but significant improvement in hip bone density , did not significantly reduce hip fracture , and increased the risk of kidney stones . ( Clinical Trials.gov number , NCT00000611 . )", "IMPORTANCE Observational data link low 25-hydroxyvitamin D levels to both prevalent blood pressure and incident hypertension . No clinical trial has yet examined the effect of vitamin D supplementation in isolated systolic hypertension , the most common pattern of hypertension in older people . OBJECTIVE To test whether high-dose , intermittent cholecalciferol supplementation lowers blood pressure in older patients with isolated systolic hypertension . DESIGN Parallel group , double-blind , placebo-controlled r and omized trial . SETTING Primary care clinics and hospital clinics . PARTICIPANTS Patients 70 years and older with isolated systolic hypertension ( supine systolic blood pressure > 140 mm Hg and supine diastolic blood pressure INTERVENTIONS A total of 100,000 U of oral cholecalciferol or matching placebo every 3 months for 1 year . MAIN OUTCOMES AND MEASURES Difference in office blood pressure , 24-hour blood pressure , arterial stiffness , endothelial function , cholesterol level , insulin resistance , and b-type natriuretic peptide level during 12 months . RESULTS A total of 159 participants were r and omized ( mean age , 77 years ) . Mean baseline office systolic blood pressure was 163/78 mm Hg . Mean baseline 25-hydroxyvitamin D level was 18 ng/mL. 25-Hydroxyvitamin D levels increased in the treatment group compared with the placebo group ( + 8 ng/mL at 1 year , P ) office blood pressure ( −1 [ −6 to 4]/−2 [ −4 to 1 ] mm Hg at 3 months and 1 [ −2 to 4]/0 [ −2 to 2 ] mm Hg overall treatment effect ) . No significant treatment effect was evident for any of the secondary outcomes ( 24-hour blood pressure , arterial stiffness , endothelial function , cholesterol level , glucose level , and walking distance ) . There was no excess of adverse events in the treatment group , and the total number of falls was nonsignificantly lower in the group receiving vitamin D ( 36 vs 46 , P = .24 ) . CONCLUSIONS AND RELEVANCE Vitamin D supplementation did not improve blood pressure or markers of vascular health in older patients with isolated systolic hypertension . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N92186858", "Daily vitamin D in addition to calcium supplementation reduces falls and fractures in older women . However , poor adherence to therapy is a common clinical problem . To examine the effects of supervised oral 3-monthly vitamin D therapy on falls , muscle strength , and mobility , we conducted a 9-month r and omized , double-blind , placebo-controlled trial in 686 community-dwelling ambulant women aged over 70 years . Participants received either oral cholecalciferol 150,000 IU every 3 months ( n = 353 ) or an identical placebo ( n = 333 ) . All participants were advised to increase dietary calcium intake . Falls data were collected 3-monthly . At baseline , 3 , 6 , and 9 months , muscle strength was measured by a h and held dynamometer and mobility by the Timed Up and Go ( TUG ) test . Serum 25 hydroxyvitamin D ( 25OHD ) was measured in a subgroup of 40 subjects . Mean age at baseline was 76.7 ± 4.1 years . The average serum 25OHD value at baseline was 65.8 ± 22.7 nmol/L. By 3 , 6 , and 9 months after supplementation , 25OHD levels of the vitamin D group were approximately 15 nmol/L higher than the placebo group . Calcium intake did not change significantly between baseline ( 864 ± 412 mg/day ) and 9 months ( 855 ± 357 mg/day ) . Faller rates in the two groups did not differ : vitamin D group , 102 of 353 ( 29 % ) ; placebo group , 89 of 333 ( 27 % ) . At 9 months , compared to placebo or baseline , muscle strength , and TUG were not altered by vitamin D. In conclusion , oral cholecalciferol 150,000 IU therapy administered 3-monthly had neither beneficial nor adverse effects on falls or physical function . These data together with previous findings confirm that intermittent large doses of vitamin D are ineffective or have a deleterious effect on falls . Thus despite adherence issues with daily vitamin D replacement , an intermittent , high-dose vitamin D regimen can not be supported as a strategy to reduce falls and fractures", "CONTEXT Observational studies have reported an inverse association between serum 25-hydroxyvitamin D ( 25-OHD ) levels and incidence of upper respiratory tract infections ( URTIs ) . However , results of clinical trials of vitamin D supplementation have been inconclusive . OBJECTIVE To determine the effect of vitamin D supplementation on incidence and severity of URTIs in healthy adults . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial conducted among 322 healthy adults between February 2010 and November 2011 in Christchurch , New Zeal and . INTERVENTION Participants were r and omly assigned to receive an initial dose of 200,000 IU oral vitamin D3 , then 200,000 IU 1 month later , then 100,000 IU monthly ( n = 161 ) , or placebo administered in an identical dosing regimen ( n = 161 ) , for a total of 18 months . MAIN OUTCOME MEASURES The primary end point was number of URTI episodes . Secondary end points were duration of URTI episodes , severity of URTI episodes , and number of days of missed work due to URTI episodes . RESULTS The mean baseline 25-OHD level of participants was 29 ( SD , 9 ) ng/mL. Vitamin D supplementation result ed in an increase in serum 25-OHD levels that was maintained at greater than 48 ng/mL throughout the study . There were 593 URTI episodes in the vitamin D group and 611 in the placebo group , with no statistically significant differences in the number of URTIs per participant ( mean , 3.7 per person in the vitamin D group and 3.8 per person in the placebo group ; risk ratio , 0.97 ; 95 % CI , 0.85 - 1.11 ) , number of days of missed work as a result of URTIs ( mean , 0.76 days in each group ; risk ratio , 1.03 ; 95 % CI , 0.81 - 1.30 ) , duration of symptoms per episode ( mean , 12 days in each group ; risk ratio , 0.96 ; 95 % CI , 0.73 - 1.25 ) , or severity of URTI episodes . These findings remained unchanged when the analysis was repeated by season and by baseline 25-OHD levels . CONCLUSION In this trial , monthly administration of 100,000 IU of vitamin D did not reduce the incidence or severity of URTIs in healthy adults . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12609000486224", "OBJECTIVES We investigated the incidence of new non-vertebral fractures during HRT or low-dose vitamin ( Vit ) D3 supplementation in a 5-year prospect i ve trial . METHODS A total of 464 early postmenopausal women , ( a subgroup of the Kuopio Osteoporosis Study , n = 13100 ) were r and omized to four groups : ( 1 ) HRT , a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate ; ( 2 ) Vit D ( 300 IU/day and 100 IU/day during the fifth year ) ; ( 3 ) HRT + Vit D ; and ( 4 ) placebo . Lumbar ( L2 - 4 ) and femoral neck bone mineral densities ( BMD ) were determined by dual X-ray absorptiometry ( DXA ) at baseline , after 2.5 and 5 years of treatment . All new symptomatic non-vertebral , radiographically defined fractures were recorded . RESULTS Altogether , 368 women ( 79 % ) completed the 5 year treatment . In all , 32 women had 39 non-vertebral fractures during a mean of 4.3 year follow-up ( HRT 4 , Vit D 10 , HRT + Vit D 8 and placebo 17 ) . The reduction in the incidence of new non-verterbral fractures was significant in women with HRT alone ( P = 0.032 ) when adjusted by baseline BMD and previous fractures ; observed also with the intention-to-treat principle ( P = 0.048 ) . When the HRT groups were pooled , HRT showed a significantly lower incidence of new non-vertebral fractures ( P = 0.042 ) than women receiving placebo and also after adjusting as above ( P = 0.016 ) ; both in valid-case and in the intention-to-treat analysis . In the Vit D group , the fracture incidence was non-significantly decreased ( P = 0.229 ) in comparison with the placebo group . The estimated risk of new non-vertebral fractures among women treated with HRT alone was 0.29 ( 95 % CI , 0.10 - 0.90 ) and with Vit D 0.47 ( 95 % CI , 0.20 - 1.14 ) and with HRT + Vit D 0.44 ( 95 % CI , 0.17 - 1.15 ) , in comparison with the placebo group ( adjusted by femoral BMD and previous fractures ) . CONCLUSIONS This study is the first prospect i ve trial confirming the beneficial effect of HRT on prevention of peripheral fractures in non-osteoporotic postmenopausal women . The effect of low-dose Vit D remains to be proved", "Objective : Vitamin D supplementation may be required for certain subgroups in the United States in whom status and intake are inadequate , but the impact of various doses , and whether calcium administration jointly or independently influences vitamin D metabolite levels , is unclear . Methods : In a pilot chemoprevention trial of biomarkers of risk for colorectal adenoma , we measured the impact of vitamin D supplementation and /or calcium supplementation on plasma vitamin D metabolite concentrations . Ninety-two adult men and women living in the southeastern United States were r and omized to 800 IU vitamin D3 , 2000 mg elemental calcium , both , or placebo daily for 6 months . We examined vitamin D status at baseline and postintervention and compared the change in plasma 25-hydroxyvitamin D ( 25(OH)D ) and 1,25(OH)2D levels by intervention group using general linear models . Results : Eighty-two percent of the study population had insufficient plasma 25(OH)D concentrations ( African American participants . Vitamin D supplements , with or without calcium supplementation , raised plasma 25(OH)D concentrations , on average , by 25 to 26 nmol/L. Half of the study participants were classified as having sufficient 25(OH)D status after 6 months of 800 IU of vitamin D3 daily . Calcium alone did not influence 25(OH)D concentrations . Conclusion : In this southeastern U.S. population , half of the study participants receiving 800 IU vitamin D3 daily had blood 25(OH)D concentrations of ≤75 nmol/L after a 6-month intervention period , supporting higher vitamin D dose requirements estimated by some groups . More research is needed to identify the optimal vitamin D dose to improve 25(OH)D status in various at-risk population", "Although calcium and vitamin-D intake were consistently shown to be inversely associated with colorectal cancer risk in several large prospect i ve studies and protective against adenoma and cancer in multiple r and omized trials , the Women 's Health Initiative ( WHI ) of calcium and low-dose vitamin-D supplementation trial found no overall effects on colorectal cancer . However , the previous report did not recognize an important biologic interaction with estrogen therapy . We investigated the treatment interaction of estrogen with calcium and vitamin-D on risk of colorectal cancer via a re analysis of primary data results from the WHI calcium and vitamin-D supplementation trial ( 1,000 mg elemental calcium , 400 IU of vitamin-D3 , or placebo ) , reanalyzing results from women concurrently r and omized to estrogen interventions and placebo . Results indicate that concurrent estrogen therapy was a strong effect modifier of calcium and vitamin-D supplementation on colorectal cancer risk . While calcium plus vitamin-D supplementation among women concurrently assigned to estrogen therapies suggested increased risk ( Hazard Ratio = 1.50 , 95 % CI : 0.96 - 2.33 ) , among women concurrently assigned to placebos arms of the estrogen trials , calcium plus vitamin-D indicated suggestive benefits ( HR = 0.71 , 95 % CI : 0.46 - 1.09 ) ( p-for-estrogen-interaction = 0.018 ) . Consistent interaction was also found by reported estrogen use ( p interaction = 0.037 ) . Results indicate contrasting effects of calcium and vitamin-D by concurrent estrogen therapy on colorectal cancer risk . Although further clinical and mechanistic studies are warranted , the potential clinical implication s of the apparent interaction of estrogen therapy with calcium and vitamin-D supplementation should be recognized . Important biological mechanisms related to the key membrane receptor megalin and estrogen-dependent protein calbindin are discussed", "Abstract . The long-term effects on bone of estrogen therapy ( HRT ) combined with vitamin D3 supplementation were evaluated and compared with the effects of HRT without vitamin D3 supplementation in a 4-year prospect i ve , partly r and omized study among 60 osteoporotic women ( mean age 55.4 years ; range 49.7–59.4 years ) . The women studied were a subgroup of the population -based Kuopio Osteoporosis Risk Factor and Prevention Study ( OSTPRE ) ( n = 13100 ) . The bone mineral densities ( BMD ) of the lumbar spine and femoral neck were determined by dual-energy X-ray absorptiometry ( DXA ) in 3236 perimenopausal women . Those 106 women with baseline BMD more than 2 SDs less than the mean value in this population , either at the lumbar spine ( BMD , were offered treatment for osteoporosis . After exclusions , 60 women were included in the analyses . Group allocation was : HRT ( estradiol valerate ( 2 mg ) plus cyproterone acetate , 1 mg , sequentially : ClimenR ) ( n = 21 ) ; HRT + Vit D : Climen + vitamin D3 ( cholecalciferol , 300 IU/day , no intake during June – August ) ( n = 23 ) ; controls : 16 women who refused all treatment served as a non-r and omized control group . In the HRT group , the highly significant increase in lumbar BMD was 5.4 % , 5.3 % , 4.7 % and 4.0 % after 1 , 2 , 3 and 4 years of treatment , respectively , all compared with the baseline values and with the control group . The increase in femoral neck BMD was statistically insignificant ( 1.4 % , 2.2 % , 1.9 % and 2.1 % , respectively ; p > 0.05 ) . In the HRT + Vit D group , the lumbar BMD increased by 3.7 % , 4.9 % , 4.9 % and 4.9 % ( p 5.8 % increase in femoral neck BMD reached significance at 4 years ( p no statistically significant differences in lumbar or femoral BMD changes between the two HRT groups . In conclusion , estrogen can substantially increase lumbar bone mass in patients with postmenopausal osteoporosis . In addition , the combination of HRT and vitamin D3 may increase femoral neck BMD in osteoporotic women more than estrogen alone", "BACKGROUND . Several factors may increase fracture risk , among them reduced bone mineral density ( BMD ) , increased bone resorption , microarchitectural deterioration of bone , increased fall risk , and decreased muscle strength . We have previously reported that PvuII polymorphism of the estrogen receptor-α ( ER α ) gene is associated with bone loss rate , fracture risk , and response to hormone replacement therapy ( HRT ) in early postmenopausal Finnish women . METHOD . We studied the influence of the ERα genotype on fall risk and muscle strength in a 5-year r and omized HRT trial of 331 early postmenopausal women ( subgroup of the population -based OSTPRE study , Kuopio , Finl and ) . A 5-year postal inquiry in May 1994 included questions on falls during the previous 12 months . Grip strength was measured with dynamometer . The ERα gene polymorphism was analysed using PCR and PvuII restriction enzyme digestion . RESULTS . In all , 97 out of the 331 women reported falls . Half of those ( 56 % ) were slip falls , mostly during the winter season . In the HRT group , the ERα genotype was associated with fall risk ( P = 0.002 , logistic regression ) . The risk of falls ( RR ) was higher in women with the PP genotype than in those with the Pp ( RR = 5.26 , 95 % CI 1.98 - 13.94 , P = 0.001 ) or the pp ( RR = 3.84 , 95 % CI 1.46 - 10.12 , P = 0.007 ) genotype . When the falls were divided into slip ( environment-related ) and non-slip ( endogenous ) falls , the non-slip falls were associated with the genotype ( P = 0.004 ) , but the slip falls were not so clearly ( P = 0.061 ) . When all falls and non-slip falls were adjusted to the number of chronic health disorders and the variable time-since-menopause , the difference between the genotypes persisted ( P = 0.003 and P = 0.010 , respectively ) . In the non-HRT group , the ERα genotype was not associated with fall risk . The baseline or the 5-year grip strength values were not influenced by the ERα genotype . In conclusion , ER α polymorphism is associated with fall risk , especially with non-slip falls , in early postmenopausal Finnish women during the HRT . We have previously reported that , during HRT , women with the P allele have decreased fracture risk and that they may preferentially derive benefit from the positive effect of HRT on BMD . This suggests that the influence of ERα polymorphism may depend on the target tissue ( bone versus the nervous system ) . CONCLUSIONS . In these early postmenopausal , non-osteoporotic and relatively healthy women , the increased fall risk associated with the PP genotype was not associated with increased fracture risk , possibly due to improved bone strength during the HRT although falls generally predispose to fractures", "Genetic factors regulate bone mineral density ( BMD ) and possibly the development of osteoporosis . An association between estrogen receptor ( ER ) polymorphism , BMD , and postmenopausal hormone replacement therapy ( HRT ) has not been established . Therefore , we studied the influence of the ER genotype on BMD before and after a 5-year HRT in a placebo-controlled , population -based , r and omized group of 322 early postmenopausal women . The participants were r and omized into two treatment groups : the HRT group ( n = 145 ) received a sequential combination of 2 mg estradiol valerate and 1 mg CPA with or without vitamin D3 , 100 - 300 IU + 500 mg calcium lactate/day ( equal to 93 mg Ca2 + ) , and the non-HRT group ( n = 177 ) received calcium lactate , 500 mg alone or in combination with vitamin D3 , 100 - 300 IU/day . PvuII restriction fragment length polymorphism ( RFLP ) of the ERalpha was determined using polymerase chain reaction ( PCR ) . BMDs of the lumbar spine ( L2 - 4 ) and proximal femur were measured by using dual-energy X-ray absorptiometry ( DXA ) . At the baseline , there were no significant differences in the lumbar or femoral neck BMDs between the three ER PvuII genotype groups ( PP , Pp , pp ) . After 5 years , the BMD of the femoral neck remained unaltered and that of the lumbar spine increased by 1.7 % in the HRT group , whereas both BMDs were decreased by 4 - 5 % in the non-HRT group . The ER genotype did not modulate the femoral neck BMD change during the follow-up . In contrast , in the non-HRT-group the lumbar spine BMD decreased more in subjects with the ER genotypes PP ( 6.4 % ) and Pp ( 5.2 % ) than in subjects with the pp genotype ( 2.9 % ) ( p = 0.002 ) . In the HRT group , the relative changes of the lumbar spine BMD were similar in all three ER genotype groups . Thus without HRT , the pp genotype was associated with a smaller decrease in the lumbar spine BMD than the Pp and PP genotypes . Long-term HRT seemed to eliminate the ER genotype-related differences in the BMD . We conclude that subjects with the ER PvuII genotypes PP and Pp may have a greater risk of relatively fast bone loss after menopause than those with the pp genotype and that they may preferentially derive benefit from HRT", "PURPOSE Vitamin D has been linked to breast cancer risk , but prognostic effects are unknown . Such effects are biologically plausible given the presence of vitamin D receptors in breast cancer cells , which act as nuclear transcription factors to regulate gene activity . PATIENTS AND METHODS The study was conducted in a prospect i ve inception cohort of 512 women with early breast cancer diagnosed 1989 to 1996 . Vitamin D levels were measured in stored blood . Clinical , pathologic , and dietary data were accessed to examine prognostic effects of vitamin D. RESULTS Mean age was 50.4 years , mean vitamin D was 58.1 + /- 23.4 nmol/L. Vitamin D levels were deficient ( 72 nmol/L ) in 24.0 % of patients . There was little variation in mean vitamin D levels between summer and winter months . Mean follow-up was 11.6 years ; 116 women had distant recurrences , and 106 women died . Women with deficient vitamin D levels had an increased risk of distant recurrence ( hazard ratio [ HR ] = 1.94 ; 95 % CI , 1.16 to 3.25 ) and death ( HR = 1.73 ; 95 % CI , 1.05 to 2.86 ) compared with those with sufficient levels . The association remained after individual adjustment for key tumor and treatment related factors but was attenuated in multivariate analyses ( HR = 1.71 ; 95 % CI , 1.02 to 2.86 for distant recurrence ; HR = 1.60 ; 95 % CI , 0.96 to 2.64 for death ) . CONCLUSION Vitamin D deficiency may be associated with poor outcomes in breast cancer", "The long term effects of hormone replacement therapy ( HRT ) and vitamin D3 ( Vit D ) on bone mineral density ( BMD ) were studied . A total of 464 nonosteoporotic early postmenopausal women from the Kuopio Osteoporosis Study ( n = 13100 ) were r and omized to four groups : 1 ) HRT ( sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate , 2 ) Vit D3 ( 300 and 100 IU/day during the fifth year ) , 3 ) HRT and Vit D combined , and 4 ) placebo . Lumbar ( L2-L4 ) and femoral neck BMD were determined by dual x-ray absorptiometry ( DXA ) at baseline and after 2.5 and 5 yr of treatment . Intention to treat analysis ( n = 464 ) showed that after 5 yr , lumbar BMD remained unchanged in the HRT and HRT plus Vit D groups [ + 0.2 % ( P = 0.658 ) and + 0.9 % ( P = 0.117 ) , respectively ] , whereas lumbar BMD decreased by 4.6 % in the Vit D group and by 4.5 % in the placebo group ( P loss of femoral neck BMD was less in the HRT ( -1.4 % ; P = 0.005 ) and HRT plus Vit D ( -1.3 % ; P = 0.003 ) groups than in the Vit D and placebo groups ( -4.3 % ; P 370 women who complied with the 5-yr treatment , the effect was more pronounced : lumbar BMD had increased by 1.5 % in the HRT ( P = 0.009 ) and by 1.8 % in the HRT plus Vit D group ( P = 0.005 ) , with a plateau after 2.5 yr , whereas lumbar BMD had decreased in both the Vit D and placebo groups ( 4.6 % and 4.7 % ; P Femoral neck BMD decreased again less in the HRT ( -0.4 % ) and HRT plus Vit D ( -0.6 % ) groups than in the Vit D and placebo groups ( -4.4 % in both ) . This study confirms the positive long term effect of HRT on BMD also seen in intention to treat analysis . The data suggest that low dose vitamin D3 supplementation does not prevent bone loss in healthy , nonosteoporotic , early postmenopausal women , and it confers no benefit additional to that of HRT alone ", "The long-term effects of calcium and vitamin D supplementation on bone material and structural properties in older men are not known . The aim of this study was to examine the effects of high calcium ( 1000 mg/day)- and vitamin-D(3 ) ( 800 IU/day)-fortified milk on cortical and trabecular volumetric BMD ( vBMD ) and bone geometry at the axial and appendicular skeleton in men aged over 50 years . One hundred and eleven men who were part of a larger 2-year r and omized controlled trial had QCT scans of the mid-femur and lumbar spine ( L(1)-L(3 ) ) to assess vBMD , bone geometry and indices of bone strength [ polar moment of inertia ( I(polar ) ) ] . After 2 years , there were no significant differences between the milk supplementation and control group for the change in any mid-femur or L(1)-L(3 ) bone parameters for all men aged over 50 years . However , the mid-femur skeletal responses to the fortified milk varied according to age , with a split of 62 years being the most significant for discriminating the changes between the two groups . Subsequent analysis revealed that , in the older men ( > 62 years ) , the expansion in mid-femur medullary area was 2.8 % ( P milk supplementation compared to control group , which helped to preserve cortical area in the milk supplementation group ( between group difference 1.1 % , P mid-femur cortical vBMD and I(polar ) , the net loss was 2.3 and 2.8 % less in the milk supplementation compared to control group ( P calcium-vitamin-D(3)-fortified milk may represent an effective strategy to maintain bone strength by preventing endocortical bone loss and slowing the loss in cortical vBMD in elderly men", "OBJECTIVE The adequate dose of vitamin D supplementation for community-dwelling elderly people has not been thoroughly investigated . This study aims to determine the efficacy of a low-dose and a higher dose of vitamin D3 in maintaining 25-hydroxyvitamin D [ 25(OH)D ] levels at or above 30 ng/mL. METHODS This was a single site , double-blind , r and omized exploratory clinical trial that enrolled adults 65 years of age and older . Within strata of baseline 25(OH)D levels ( subjects were r and omized in a 1:2 ratio to receive either 400 or 2,000 IU vitamin D3 daily for 6 months . The main outcome measures were changes in serum 25(OH)D levels according to baseline 25(OH)D levels and dose of vitamin D3 . RESULTS At baseline , 41 of 105 participants ( 39 % ) had low 25(OH)D levels ( months of vitamin D3 supplementation , 21 of 32 participants ( 66 % ) receiving 400 IU and 14 of 59 participants ( 24 % ) receiving 2,000 IU of vitamin D3 still had low 25(OH)D levels . The largest increases in serum 25(OH)D levels were observed in subjects with baseline levels persons 65 years of age and older , 6-month vitamin D3 supplementation with 400 IU daily result ed in low 25(OH)D in most individuals , while 2,000 IU daily maintained 25(OH)D levels within an acceptable range in most people on this regimen", "BACKGROUND Current unitage for the calciferols suggests that equimolar quantities of vitamins D(2 ) ( D2 ) and D(3 ) ( D3 ) are biologically equivalent . Published studies yield mixed results . OBJECTIVE The aim of the study was to compare the potencies of D2 and D3 . DESIGN The trial used a single-blind , r and omized design in 33 healthy adults . Calciferols were dosed at 50,000 IU/wk for 12 wk . Principal outcome variables were area under the curve for incremental total 25-hydroxyvitamin D [ 25(OH)D ] and change in calciferol content of sc fat . RESULTS Incremental mean ( sd ) 25(OH)D area under the curve at 12 wk was 1366 ng · d/ml ( 516 ) for the D2-treated group and 2136 ( 606 ) for the D3 ( P 0.001 ) . Mean ( sd ) steady-state 25(OH)D increments showed similar differences : 24 ng/ml for D2 ( 10.3 ) and 45 ng/ml ( 16.2 ) for D3 ( P 0.001 ) . Subcutaneous fat content of D2 rose by 50 μg/kg in the D2-treated group , and D3 content rose by 104 μg/kg in the D3-treated group . Total calciferol in fat rose by only 33 ng/kg in the D2-treated , whereas it rose by 104 μg/kg in the D3-treated group . Extrapolating to total body fat D3 , storage amounted to just 17 % of the administered dose . CONCLUSION D3 is approximately 87 % more potent in raising and maintaining serum 25(OH)D concentrations and produces 2- to 3-fold greater storage of vitamin D than does equimolar D2 . For neither was there evidence of sequestration in fat , as had been postulated for doses in this range . Given its greater potency and lower cost , D3 should be the preferred treatment option when correcting vitamin D deficiency", "Data from laboratory studies , observational research , and /or secondary prevention trials suggest that vitamin D and marine omega-3 fatty acids may reduce risk for cancer or cardiovascular disease ( CVD ) , but primary prevention trials with adequate dosing in general population s ( i.e. , unselected for disease risk ) are lacking . The ongoing VITamin D and OmegA-3 TriaL ( VITAL ) is a large r and omized , double-blind , placebo-controlled , 2 x 2 factorial trial of vitamin D ( in the form of vitamin D(3 ) [ cholecalciferol ] , 2000 IU/day ) and marine omega-3 fatty acid ( Omacor fish oil , eicosapentaenoic acid [EPA]+docosahexaenoic acid [ DHA ] , 1g/day ) supplements in the primary prevention of cancer and CVD among a multi-ethnic population of 20,000 U.S. men aged ≥ 50 and women aged ≥ 55 . The mean treatment period will be 5 years . Baseline blood sample s will be collected in at least 16,000 participants , with follow-up blood collection in about 6000 participants . Yearly follow-up question naires will assess treatment compliance ( plasma biomarker measures will also assess compliance in a r and om sample of participants ) , use of non- study drugs or supplements , occurrence of endpoints , and cancer and vascular risk factors . Self-reported endpoints will be confirmed by medical record review by physicians blinded to treatment assignment , and deaths will be ascertained through national registries and other sources . Ancillary studies will investigate whether these agents affect risk for diabetes and glucose intolerance ; hypertension ; cognitive decline ; depression ; osteoporosis and fracture ; physical disability and falls ; asthma and other respiratory diseases ; infections ; and rheumatoid arthritis , systemic lupus erythematosus , thyroid diseases , and other autoimmune disorders", "CONTEXT Public health authorities around the world recommend widely variable supplementation strategies for adults , whereas several professional organizations , including The Endocrine Society , recommend higher supplementation . METHODS We analyzed published r and omized controlled clinical trials to define the optimal intake or vitamin D status for bone and extraskeletal health . CONCLUSIONS The extraskeletal effects of vitamin D are plausible as based on pre clinical data and observational studies . However , apart from the beneficial effects of 800 IU/d of vitamin D3 for reduction of falls in the elderly , causality remains yet unproven in r and omized controlled trials ( RCTs ) . The greatest risk for cancer , infections , cardiovascular and metabolic diseases is associated with 25-hydroxyvitamin D ( 25OHD ) levels below 20 ng/mL. There is ample evidence from RCTs that calcium and bone homeostasis , estimated from serum 1,25-dihydroxyvitamin D and PTH , calcium absorption , or bone mass , can be normalized by 25OHD levels above 20 ng/mL. Moreover , vitamin D supplementation ( 800 IU/d ) in combination with calcium can reduce fracture incidence by about 20 % . Such a dose will bring serum levels of 25OHD above 20 ng/mL in nearly all postmenopausal women . Based on calculations of the metabolic clearance of 25OHD , a daily intake of 500 - 700 IU of vitamin D3 is sufficient to maintain serum 25OHD levels of 20 ng/mL. Therefore , the recommendations for a daily intake of 1500 - 2000 IU/d or serum 25OHD levels of 30 ng or higher for all adults or elderly subjects , as suggested by The Endocrine Society Task Force , are premature . Fortunately , ongoing RCTs will help to guide us to solve this important public health question", "BACKGROUND . After the menopause , estrogen synthesis from and rogens and and rogen precursors by aromatase is the main source of circulating estrogens . AIM . To evaluate whether aromatase gene (CYP19)polymorphism affects circulating estradiol ( E[Formula : See Text])levels , bone mineral density ( BMD ) , BMD change or fracture risk . METHODS . A 5-year r and omized hormone replacement therapy ( HRT ) trial on 331 early postmenopausal women ( mean baseline age 52.7 ± 2.3 years ) . The participants consisted of two treatment groups : the HRT group ( n = 151 ) received a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate with or without vitamin D[Formula : See Text ] , 100 - 300 IU + 93 mg calcium as lactate/day , and the non-HRT group ( n = 180 ) received 93 mg calcium alone or in combination with vitamin D[Formula : See Text ] , 100 - 300 IU/day for 5 years . BMD was measured from lumbar spine and proximal femur ( DXA ) before and after the 5-year trial . All new symptomatic , radiographically defined fractures were recorded during the follow-up . The polymorphism ( intron 4 TTTA repeat ) of CYP19 was evaluated after PCR amplification of the polymorphic site . CYP19 polymorphism was divided into three repeat groups : short ( length of 7 or 8 in both alleles ; n = 135 ) , long ( length of 11 or higher in both alleles ; n = 47 ) , and medium ( rest of the values ; n = 149 ) . RESULTS . Of the baseline characteristics , only physical activity was associated with CYP19 polymorphism ( P = 0.04 ) and a borderline significance was observed with previous fractures ( P = 0.05 ) . In the HRT or non-HRT groups , the 5-year serum E[Formula : See Text ] change was not associated with CYP19 polymorphism ( P = 0.87 and 0.74 , respectively ) . Further , the polymorphism did not influence the calculated annual changes of lumbar or femoral neck BMD during the 5-year follow-up in the HRT ( P = 0.60 and 0.17 , respectively ) or non-HRT ( P = 0.92 and 0.80 , respectively ) groups . In all , 28 women sustained 33 fractures during the follow-up . The CYP19 polymorphism was not significantly associated with fracture risk ( P = 0.89 and 0.23 respectively ; Cox proportional hazards model ) in the HRT or non-HRT groups . CONCLUSIONS .CYP19 polymorphism was not associated with circulating E[Formula : See Text ] levels , BMD values , or fracture risk in these early postmenopausal Finnish women . If such an association exists in women , it may become apparent in older age groups", "Summary Vitamin D may affect skeletal muscle function . In a double-blind , r and omised , placebo-controlled trial , we found that vitamin D3 supplementation ( 400 or 1,000 I.U. vs. placebo daily for 1 year with bimonthly study visits ) does not improve grip strength or reduce falls . Introduction This study aim ed to test the supplementation effects of vitamin D3 on physical function and examine associations between overweight/obesity and the biochemical response to treatment . Methods In a parallel group double-blind RCT , healthy postmenopausal women from North East Scotl and ( latitude—57 ° N ) aged 60–70 years ( body mass index ( BMI ) , 18–45 kg/m2 ) were assigned ( computer r and omisation ) to daily vitamin D3 ( 400 I.U. ( n = 102)/1,000 I.U. ( n = 101 ) ) or matching placebo ( n = 102 ) ( 97 , 96 and 100 participants analysed for outcomes , respectively ) from identical coded containers for 1 year . Grip strength ( primary outcome ) , falls , diet , physical activity and ultraviolet B radiation exposure were measured bimonthly , as were serum 25(OH)D , adjusted calcium ( ACa ) and phosphate . Fat/lean mass ( dual energy X-ray absorptiometry ) , anthropometry , 1,25-dihydroxyvitamin D and parathyroid hormone were measured at baseline and 12 months . Participants and research ers were blinded throughout intervention and analysis . Results Treatment had no effect on grip strength ( mean change (SD)/year = −0.5 ( 2.5 ) , −0.9 ( 2.7 ) and −0.4 ( 3.3 ) kg force for 400/1,000 I.U. vitamin D3 and placebo groups , respectively ( P = .10 , ANOVA ) ) or falls ( P = .65 , chi-squared test ) . Biochemical responses were similar across BMI categories ( in serum ACa in overweight compared to non-overweight participants ( P = .01 , ANOVA ; 1,000 I.U. group ) . In the placebo group , 25(OH)D peak concentration change ( winter to summer ) was negatively associated with weight ( r = −.268 ) , BMI ( r = −.198 ) , total ( r = −.278 ) and trunk fat mass ( r = −.251 ) , with total and trunk fat mass predictive of winter to summer 25(OH)D change ( P = .01/.004 respectively , linear regression ) . Conclusion We found no evidence of an improvement in physical function following vitamin D3 supplementation for 1 year", "There is an increase in the incidence of falls with aging and about 10 % of falls lead to fractures . Nearly all hip fractures are due to falls and hip fractures are the most severe of the osteoporotic fractures because they lead to a 20 % mortality rate and a loss of independent living in 50 % of cases . Although there are multiple factors associated with falls , our interest is the role that vitamin D metabolism plays in the pathogenesis of falls . Recent clinical trials show that both vitamin D and the metabolite calcitriol reduce the number of falls by 30 - 40 % in elderly subjects . This should also reduce the number of fractures . In European studies , the decrease in falls could be attributed to an improvement in the muscle weakness that often accompanies vitamin D deficiency . However , in the studies using calcitriol there was no vitamin D deficiency , so the mechanism of its efficacy is less clear . It could be due to increased muscle strength , an improvement in the neurological control of balance or both . Underst and ing these mechanisms would allow us to search for analogs of vitamin D that act more selectively on muscle and on the central nervous system", "Experimental evidence provides strong support for anti-carcinogenic effects of calcium and vitamin D with respect to breast cancer . Observational epidemiologic data also provide some support for inverse associations with risk . We tested the effect of calcium plus vitamin D supplementation on risk of benign proliferative breast disease , a condition which is associated with increased risk of breast cancer . We used the Women ’s Health Initiative r and omized controlled trial . The 36,282 participants were r and omized either to 500 mg of elemental calcium as calcium carbonate plus 200 IU of vitamin D3 ( GlaxoSmithKline ) twice daily ( n = 18,176 ) or to placebo ( n = 18,106 ) . Regular mammograms and clinical breast exams were performed . We identified women who had had a biopsy for benign breast disease and subjected histologic sections from the biopsies to st and ardized review . After an average follow-up period of 6.8 years , 915 incident cases of benign proliferative breast disease had been ascertained , with 450 in the intervention group and 465 in the placebo group . Calcium plus vitamin D supplementation was not associated with altered risk of benign proliferative breast disease overall ( hazard ratio = 0.99 , 95 % confidence interval = 0.86–1.13 ) , or by histologic subtype . Risk varied significantly by levels of age at baseline , but not by levels of other variables . Daily use of 1,000 mg of elemental calcium as calcium carbonate plus 400 IU of vitamin D3 for almost 7 years by postmenopausal women did not alter the overall risk of benign proliferative breast disease", "OBJECTIVE In contrast to age-matched men , endurance exercise training is not consistently associated with enhanced endothelial function in estrogen-deficient postmenopausal women . We determined whether endurance exercise training improves endothelial function in postmenopausal women treated with estrogen . In a sub study , we determined if oxidative stress is mechanistically linked to endothelial function adaptations to endurance exercise training . PARTICIPANTS AND DESIGN Brachial artery flow-mediated dilation ( FMD ) was measured in 36 sedentary , estrogen-deficient postmenopausal women ( 45 - 65 y ) at study entry ( baseline ) , after 12 weeks of either placebo , oral ( 1 mg/d ) estradiol , or transdermal estradiol ( 0.05 mg/d ) ( r and omized ) , and after an additional 12 weeks of continued estradiol or placebo treatment with concurrent endurance exercise training . In subgroups of women , FMD also was measured during the infusion of ascorbic acid at baseline and following estradiol/placebo plus endurance exercise training , and in seven habitually endurance-trained estrogen-deficient controls . RESULTS FMD increased in the estrogen-treated groups ( both P placebo . FMD further increased following 12 weeks of endurance exercise training in estrogen-treated ( both P placebo-treated women ( P = .55 ) . In the sub study , baseline FMD was similar between sedentary and endurance-trained controls . Ascorbic acid increased FMD at baseline in sedentary women and endurance-trained controls , and following endurance exercise training in placebo-treated , but not in estrogen-treated women . CONCLUSIONS Estrogen status appears to play an important modulatory role in improvements in endothelial function with endurance exercise training in postmenopausal women . The restored endurance exercise training adaptation in estrogen-treated postmenopausal women may be related to mitigation of oxidative stress", "CONTEXT Vitamin D or calcium supplementation may have effects on vascular disease and cancer . OBJECTIVE Our objective was to investigate whether vitamin D or calcium supplementation affects mortality , vascular disease , and cancer in older people . DESIGN AND SETTING The study included long-term follow-up of participants in a two by two factorial , r and omized controlled trial from 21 orthopedic centers in the United Kingdom . PARTICIPANTS Participants were 5292 people ( 85 % women ) aged at least 70 yr with previous low-trauma fracture . INTERVENTIONS Participants were r and omly allocated to daily vitamin D(3 ) ( 800 IU ) , calcium ( 1000 mg ) , both , or placebo for 24 - 62 months , with a follow-up of 3 yr after intervention . MAIN OUTCOME MEASURES All-cause mortality , vascular disease mortality , cancer mortality , and cancer incidence were evaluated . RESULTS In intention-to-treat analyses , mortality [ hazard ratio ( HR ) = 0.93 ; 95 % confidence interval ( CI ) = 0.85 - 1.02 ] , vascular disease mortality ( HR = 0.91 ; 95 % CI = 0.79 - 1.05 ) , cancer mortality ( HR = 0.85 ; 95 % CI = 0.68 - 1.06 ) , and cancer incidence ( HR = 1.07 ; 95 % CI = 0.92 - 1.25 ) did not differ significantly between participants allocated vitamin D and those not . All-cause mortality ( HR = 1.03 ; 95 % CI = 0.94 - 1.13 ) , vascular disease mortality ( HR = 1.07 ; 95 % CI = 0.92 - 1.24 ) , cancer mortality ( HR = 1.13 ; 95 % CI = 0.91 - 1.40 ) , and cancer incidence ( HR = 1.06 ; 95 % CI = 0.91 - 1.23 ) also did not differ significantly between participants allocated calcium and those not . In a post hoc statistical analysis adjusting for compliance , thus with fewer participants , trends for reduced mortality with vitamin D and increased mortality with calcium were accentuated , although all results remain nonsignificant . CONCLUSIONS Daily vitamin D or calcium supplementation did not affect mortality , vascular disease , cancer mortality , or cancer incidence", "OBJECTIVES To evaluate and compare the effects and safety of high dose intramuscular ( IM ) or oral cholecalciferol on 25-hydroxyvitamin D [ 25(OH)D ] levels , muscle strength and physical performance in vitamin D deficient/insufficient elderly . STUDY DESIGN R and omized prospect i ve study . MAIN OUTCOME MEASURES 116 ambulatory individuals aged 65 years or older living in a nursing home were evaluated . Eligible patients with 25(OH)D levels were r and omized to IM or Oral groups according to the administration route of 600,000 IU cholecalciferol . Demographic and descriptive data were collected . Biochemical response was measured at baseline , 6th and 12th weeks . Muscle strength was measured from quadriceps by using a h and -held dynamometer and physical performance was evaluated by short physical performance battery ( SPPB ) at the beginning and 12th week . RESULTS Among the screened ambulatory elderly only 5.2 % ( n=6 ) had adequate vitamin D levels . 37.1 % ( n=43 ) were vitamin D deficient and 57.7 % ( n=67 ) were insufficient . After administration of one megadose of vitamin D , mean serum 25(OH)D levels increased significantly at 6th week ( 32.72±9.0 ng/ml ) and at 12th week ( 52.34±14.2 ng/ml ) compared with baseline ( 11.76±7.6 ng/ml ) in IM group ( p period , serum 25(OH)D levels were ≥30 ng/ml in all patients in IM group and in 83.3 % of the patients in the Oral group . Quadriceps muscle strength and SPPB total score increased significantly in both groups and SPPB balance subscale score increased only in IM group . Six patients ( 9.6 % ) developed hypercalciuria , no significant adverse events were observed . CONCLUSION In vitamin D deficient/insufficient elderly , a single megadose of cholecalciferol increased vitamin D levels significantly and the majority of the patients reached optimal levels . Although both administration routes are effective and appear to be safe , IM application is more effective in increasing 25(OH)D levels and balance performance", "In the GRADE approach , r and omized trials are classified as high quality evidence and observational studies as low quality evidence but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted", "The effects of four different treatment schedules on serum lipid concentrations were studied for 1 year in 402 postmenopausal women in the Kuopio Osteoporosis Study . The women were r and omized to four treatment groups : A , Sequential combination of estradiol valerate and cyproterone acetate ( Climen ) ; B , Vitamin D3 , 300 IU/day ; C , Climen+Vitamin D3 , D , placebo . In group A , serum concentrations of total cholesterol ( Chol ) decreased by 4.8 % in 6 months and by 6.2 % in 12 months ( P total-Chol in group A was accounted for by the 6.8 % to 7.5 % decrease in LDL-Chol levels ( P LDL-Chol in group C was statistically non-significant . Use of vitamin D3 ( group B ) , increased serum Chol by 2.7 % ( 6 months ) , P LDL-Chol levels in 6 and 12 months , respectively ( P Serum concentrations of HDL-Chol and TG remained relatively stable in all groups . No correlations were found between LDL-Chol , 25-OH-D3 and 1,25(OH)2-D3 levels in group B. Our results confirm the beneficial effect of estradiol valerate and cyproterone acetate on the lipid profile . In contrast , vitamin D3 had a negative influence on this profile by increasing serum concentrations of LDL-Chol . ( ABSTRACT TRUNCATED AT 250 WORDS", "PURPOSE In light of inverse relationships reported in observational studies of vitamin D intake and serum 25-hydroxyvitamin D levels with risk of nonmelanoma skin cancer ( NMSC ) and melanoma , we evaluated the effects of vitamin D combined with calcium supplementation on skin cancer in a r and omized placebo-controlled trial . METHODS Postmenopausal women age 50 to 79 years ( N = 36,282 ) enrolled onto the Women 's Health Initiative ( WHI ) calcium/vitamin D clinical trial were r and omly assigned to receive 1,000 mg of elemental calcium plus 400 IU of vitamin D3 ( CaD ) daily or placebo for a mean follow-up period of 7.0 years . NMSC and melanoma skin cancers were ascertained by annual self-report ; melanoma skin cancers underwent physician adjudication . RESULTS Neither incident NMSC nor melanoma rates differed between treatment ( hazard ratio [ HR ] , 1.02 ; 95 % CI , 0.95 to 1.07 ) and placebo groups ( HR , 0.86 ; 95 % CI , 0.64 to 1.16 ) . In subgroup analyses , women with history of NMSC assigned to CaD had a reduced risk of melanoma versus those receiving placebo ( HR , 0.43 ; 95 % CI , 0.21 to 0.90 ; P(interaction ) = .038 ) , which was not observed in women without history of NMSC . CONCLUSION Vitamin D supplementation at a relatively low dose plus calcium did not reduce the overall incidence of NMSC or melanoma . However , in women with history of NMSC , CaD supplementation reduced melanoma risk , suggesting a potential role for calcium and vitamin D supplements in this high-risk group . Results from this post hoc subgroup analysis should be interpreted with caution but warrant additional investigation", "OBJECTIVE We evaluated the inter-rater reliability ( IRR ) of assessing the quality of evidence ( QoE ) using the Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) approach . STUDY DESIGN AND SETTING On completing two training exercises , participants worked independently as individual raters to assess the QoE of 16 outcomes . After recording their initial impression using a global rating , raters grade d the QoE following the GRADE approach . Subsequently , r and omly paired raters su bmi tted a consensus rating . RESULTS The IRR without using the GRADE approach for two individual raters was 0.31 ( 95 % confidence interval [ 95 % CI ] = 0.21 - 0.42 ) among Health Research Methodology students ( n = 10 ) and 0.27 ( 95 % CI = 0.19 - 0.37 ) among the GRADE working group members ( n = 15 ) . The corresponding IRR of the GRADE approach in assessing the QoE was significantly higher , that is , 0.66 ( 95 % CI = 0.56 - 0.75 ) and 0.72 ( 95 % CI = 0.61 - 0.79 ) , respectively . The IRR further increased for three ( 0.80 [ 95 % CI = 0.73 - 0.86 ] and 0.74 [ 95 % CI = 0.65 - 0.81 ] ) or four raters ( 0.84 [ 95 % CI = 0.78 - 0.89 ] and 0.79 [ 95 % CI = 0.71 - 0.85 ] ) . The IRR did not improve when QoE was assessed through a consensus rating . CONCLUSION Our findings suggest that trained individuals using the GRADE approach improves reliability in comparison to intuitive judgments about the QoE and that two individual raters can reliably assess the QoE using the GRADE system", "Osteoporosis is a major public health issue leading to significant morbidity , loss of independence and excess loss of life . It has been estimated that 13 to 17 million postmenopausal women have low bone mass or osteoporosis ( 1 , 2 ) . This is associated with almost 1.5 million fractures annually , including 300,000 hip fractures ( 2 , 3 ) . A review of the evidence by Cumming in 1990 ( 4 ) and subsequently published r and omized clinical trials have shown that calcium and /or vitamin D supplements may play a role in the prevention and treatment of osteoporosis by slowing the rates of bone loss in postmenopausal and elderly women ( 5–9 ) . However , there are a limited number of calcium and /or vitamin D trials ( 10–13 ) and observational studies [ review of evidence by Cumming and Nevitt ( 14 ) and Kanis ( 15 ) ] , to support a role for calcium and vitamin D supplementation in the reduction of hip and other fractures . It has also been suggested that calcium and vitamin D supplementation may play a role in the reduction of colorectal cancer incidence ( 16–21 ) . To address these major health concerns of postmenopausal women , the Calcium-Vitamin D ( CaD ) trial of the Women ’s Health Initiative ( WHI ) was design ed to test the primary hypothesis that women who are r and omized to receive calcium and vitamin D supplementation will have a lower risk of hip fracture and secondarily , a lower risk of all fractures and colorectal cancer than women receiving corresponding placebo . The objective of this paper is", "BACKGROUND Obesity in the United States has increased significantly during the past several decades . The role of calcium in the maintenance of a healthy body weight remains controversial . METHODS A r and omized , double-blinded , placebo-controlled trial was performed with 36 282 postmenopausal women , aged 50 to 79 years , who were already enrolled in the dietary modification and /or hormone therapy arms of the Women 's Health Initiative clinical trial . Women were r and omized at their first or second annual visit to receive a dose of 1000 mg of elemental calcium plus 400 IU of cholecalciferol ( vitamin D ) or placebo daily . Change in body weight was ascertained annually for an average of 7 years . RESULTS Women receiving calcium plus cholecalciferol supplements vs women receiving placebo had a minimal but consistent favorable difference in weight change ( mean difference , -0.13 kg ; 95 % confidence interval , -0.21 to -0.05 ; P = .001 ) . After 3 years of follow-up , women with daily calcium intakes less than 1200 mg at baseline who were r and omized to supplements were 11 % less likely to experience small weight gains ( 1 - 3 kg ) and 11 % less likely to gain more moderate amounts of weight ( > 3 kg ) ( P for interaction for baseline calcium intake = .008 ) . CONCLUSION Calcium plus cholecalciferol supplementation has a small effect on the prevention of weight gain , which was observed primarily in women who reported inadequate calcium intakes . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000611", "BACKGROUND The bioequivalence of the different forms of vitamin D , ergocalciferol ( vitamin D2 ) and cholecalciferol ( vitamin D3 ) , has been question ed . Earlier studies have suggested that vitamin D2 is less biologically active than vitamin D3 . OBJECTIVE AND DESIGN In a parallel study , we tested the effects of supplementation with 50-μg/d doses of vitamin D2 or D3 or a placebo over a period of 8 weeks on 25(OH)D2 , 25(OH)D3 , their sum 25(OH)D ( primary outcome variables ) , and PTH in healthy volunteers applying a double-blind , r and omized study design . The study was conducted during the winter of 2012 in Halle ( Saale ) , Germany , at latitude 51 ° 47N , when UVB irradiation is virtually absent . Blood sample s for the determinations of vitamin D status and PTH were collected at baseline and after 4 and 8 weeks of supplementation . RESULTS In the placebo group ( n = 19 ) , 25(OH)D3 decreased from 39.4 ± 14.2 to 31.1 ± 12.4 nmol/L after 8 weeks ( P the concentrations of 25(OH)D3 increased from 41.5 ± 22.8 nmol/L at baseline to 88.0 ± 22.1 nmol/L after 8 weeks ( P receiving vitamin D2 ( n = 46 ) , the 25(OH)D2 concentrations increased significantly , whereas the 25(OH)D3 concentration fell from 36.4 ± 13.3 nmol/L at baseline to 16.6 ± 6.3 nmol/L after 8 weeks ( P The total 25(OH)D was not different between the groups at baseline but differed significantly between the groups after 4 and 8 weeks ( P CONCLUSIONS Vitamin D3 increases the total 25(OH)D concentration more than vitamin D2 . Vitamin D2 supplementation was associated with a decrease in 25(OH)D3 , which can explain the different effect on total", "CONTEXT In humans , few studies have compared the potencies of ergocalciferol and cholecalciferol in improving and maintaining vitamin D status . OBJECTIVE Our objective was to evaluate the effects of a single very large dose of both calciferols on serum changes of 25-hydroxyvitamin D [ 25(OH)D ] , 1,25-dihydroxyvitamin D [ 1,25(OH)(2)D ] , ionized calcium , and parathyroid hormone ( PTH ) at baseline , and at 3 , 7 , 30 , and 60 d. DESIGN This was a prospect i ve r and omized intervention study . SETTING The study was performed in a nursing home residence . PARTICIPANTS A total of 32 elderly female patients ( age range 66 - 97 yr ) , with vitamin D deficiency was included in the study . INTERVENTION Participants were r and omized into four groups of eight to receive a single dose of 300,000 IU ergocalciferol or cholecalciferol by oral ( os ) or i m route . RESULTS 25(OH)D levels sharply increased at d 3 only when vitamins were given os . The 30-d basal difference in serum 25(OH)D was significantly greater after cholecalciferol os administration ( 47.8 + /- 7.3 ng/ml ) compared with other forms ( D(3 ) i m : 15.9 + /- 11.3 ; D(2 ) os : 17.3 + /- 4.7 ; D(2 ) i m : 5 + /- 4.4 ; all P area under the curve ( AUC ) of the serum 25(OH)D against time ( AUC(60 ) ) was : D(3 ) os , 3193 + /- 759 ng x d/ml vs. D(2 ) os , 1820 + /- 512 , P PTH levels at 3 ( P ( cholecalciferol ) significantly lowers PTH levels ( P = 0.037 ) . CONCLUSIONS Cholecalciferol is almost twice as potent as ergocalciferol in increasing serum 25(OH)D , when administered either by mouth or i m . 25(OH)D plays a role in modulating serum PTH", "BACKGROUND Elderly people who have a fracture are at high risk of another . Vitamin D and calcium supplements are often recommended for fracture prevention . We aim ed to assess whether vitamin D3 and calcium , either alone or in combination , were effective in prevention of secondary fractures . METHODS In a factorial- design trial , 5292 people aged 70 years or older ( 4481 [ 85 % ] of whom were women ) who were mobile before developing a low-trauma fracture were r and omly assigned 800 IU daily oral vitamin D3 , 1000 mg calcium , oral vitamin D3 ( 800 IU per day ) combined with calcium ( 1000 mg per day ) , or placebo . Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months . Analysis was by intention-to-treat and the primary outcome was new low-energy fractures . FINDINGS 698 ( 13 % ) of 5292 participants had a new low-trauma fracture , 183 ( 26 % ) of which were of the hip . The incidence of new , low-trauma fractures did not differ significantly between participants allocated calcium and those who were not ( 331 [ 12.6 % ] of 2617 vs 367 [ 13.7 % ] of 2675 ; hazard ratio ( HR ) 0.94 [ 95 % CI 0.81 - 1.09 ] ) ; between participants allocated vitamin D3 and those who were not ( 353 [ 13.3 % ] of 2649 vs 345 [ 13.1 % ] of 2643 ; 1.02 [ 0.88 - 1.19 ] ) ; or between those allocated combination treatment and those assigned placebo ( 165 [ 12.6 % ] of 1306 vs 179 [ 13.4 % ] of 1332 ; HR for interaction term 1.01 [ 0.75 - 1.36 ] ) . The groups did not differ in the incidence of all-new fractures , fractures confirmed by radiography , hip fractures , death , number of falls , or quality of life . By 24 months , 2886 ( 54.5 % ) of 5292 were still taking tablets , 451 ( 8.5 % ) had died , 58 ( 1.1 % ) had withdrawn , and 1897 ( 35.8 % ) had stopped taking tablets but were still providing data for at least the main outcomes . Compliance with tablets containing calcium was significantly lower ( difference : 9.4 % [ 95 % CI 6.6 - 12.2 ] ) , partly because of gastrointestinal symptoms . However , potentially serious adverse events were rare and did not differ between groups . INTERPRETATION The findings do not support routine oral supplementation with calcium and vitamin D3 , either alone or in combination , for the prevention of further fractures in previously mobile elderly people", "In the Women 's Health Initiative ( WHI ) trial of calcium plus vitamin D ( CaD ) , we examined the treatment effect on incidence and mortality for all invasive cancers . Postmenopausal women ( N = 36,282 ) were r and omized to 1,000 mg of elemental calcium with 400 IU vitamin D3 or placebo . Cox models estimated risk of cancer incidence and mortality . After 7.0 yr , 1,306 invasive cancers were diagnosed in the supplement and 1,333 in the placebo group [ hazard ratio ( HR ) = 0.98 ; CI = 0.90 , 1.05 , unweighted P = 0.54 ] . Mortality did not differ between supplement ( 315 , annualized% = .26 ) and placebo [ ( 347 , 0.28 % ; P = 0.17 ; HR = 0.90 ( 0.77 , 1.05 ) ] . Significant treatment interactions on incident cancer were found for family history of cancer , personal total intake of vitamin D , smoking , and WHI dietary trial r and omized group . Calcium/vitamin D supplementation did not reduce invasive cancer incidence or mortality . Supplementation lowered cancer risk in the WHI healthy diet trial arm and in women without a first-degree relative with cancer . The interactions are only suggestive given multiple testing considerations . The low vitamin D dose provided , limited adherence , and lack of serum 25(OH)D values should be considered when interpreting these findings", "OBJECTIVES The Women 's Health Initiative ( WHI ) r and omized trial of calcium/vitamin D supplementation found reduced bone loss with active treatment compared to placebo . Now we examine whether the treatment affected self-reported physical functioning and objective measures of physical functioning . DESIGN A r and omized , double-blind , placebo-controlled trial of 1,000 mg calcium carbonate plus 400 IU vitamin D(3 ) per day or matching placebo pills . SUBJECTS/ SETTING The study included 33,067 women ( 50 to 79 years old ) at 40 US study centers . MAIN OUTCOME MEASURES Physical functioning was assessed by question naire at enrollment in WHI , 1 year prior to calcium/vitamin D trial r and omization and at study close-out ( average follow-up 7.1 years ) . Objective physical performance and self-reported exercise measures were collected at WHI baseline ( 1 year prior to calcium/vitamin D enrollment ) and 2 years and 4 years after calcium/vitamin D trial enrollment in a sub sample ( n=3,137 ) . STATISTICAL ANALYSES PERFORMED Calcium/vitamin D effects were tested in unadjusted and interaction linear models for each of the physical function measures . Covariates were baseline total calcium intake , fracture risk score , treatment arm in the hormone therapy and dietary modification trials ( ie , active drug or placebo , low-fat diet intervention or usual diet , respectively ) and age . RESULTS Neither intention to treat nor high adherence analyses produced substantial effects of calcium/vitamin D compared to placebo on physical functioning or performance . The interaction analyses also did not result in differences because of calcium/vitamin D. CONCLUSIONS As the first long-term r and omized trial to examine the effectiveness of calcium and vitamin D in protecting against decline of physical functioning in older women , the results did not support benefit", "BACKGROUND R and omized controlled trials testing the association between vitamin D status and upper respiratory tract infection ( URTI ) have given mixed results . During a multicenter , r and omized controlled trial of colorectal adenoma chemoprevention , we tested whether 1000 IU/day vitamin D(3 ) supplementation reduced winter episodes and duration of URTI and its composite syndromes , influenza-like illness ( ILI ; fever and ≥2 of sore throat , cough , muscle ache , or headache ) and colds ( no fever , and ≥2 of runny nose , nasal congestion , sneezing , sore throat , cough , swollen or tender neck gl and s ) . METHODS The 2259 trial participants were aged 45 - 75 , in good health , had a history of colorectal adenoma , and had a serum 25-hydroxyvitamin D level ≥12 ng/mL. They were r and omized to vitamin D(3 ) ( 1000 IU/day ) , calcium ( 1200 mg/day ) , both , or placebo . Of these , 759 participants completed daily symptom diaries . Secondary data included semiannual surveys of all participants . RESULTS Among those who completed symptom diaries , supplementation did not significantly reduce winter episodes of URTI ( rate ratio [ RR ] , 0.93 ; 95 % confidence interval [ CI ] , .79 - 1.09 ) including colds ( RR , 0.93 ; 95 % CI , .78 - 1.10 ) or ILI ( RR , 0.95 ; 95 % CI , .62 - 1.46 ) , nor did it reduce winter days of illness ( RR , 1.13 ; 95 % CI , .90 - 1.43 ) . There was no significant benefit according to adherence , influenza vaccination , body mass index , or baseline vitamin D status . Semiannual surveys of all participants ( N = 2228 ) identified no benefit of supplementation on ILI ( odds ratio [ OR ] , 1.14 ; 95 % CI , .84 - 1.54 ) or colds ( OR , 1.03 ; 95 % CI , .87 - 1.23 ) . CONCLUSIONS Supplementation with 1000 IU/day vitamin D(3 ) did not significantly reduce the incidence or duration of URTI in adults with a baseline serum 25-hydroxyvitamin D level ≥12", "Objectives : To investigate the practicality and tolerability of high‐dose intramuscular ( i.m . ) vitamin D2 or oral vitamin D3 replacement in vitamin D‐insufficient patients , and to evaluate the biochemical efficacy of each formulation . Methods : Sixty‐nine patients with vitamin D insufficiency [ 25‐hydroxyvitamin D ( 25(OH)D ) In study 1 , 50 patients received 300 000 IU i.m . vitamin D2 ( ergocalciferol ) . In study 2 , 19 patients received 300 000 IU oral vitamin D3 ( cholecalciferol ) under observation . Biochemical response was measured at baseline , and at 12 and 24 weeks . Results : Bolus i.m . vitamin D2 or oral vitamin D3 was well tolerated . The change from baseline in serum 25(OH)D was significantly greater at 6 and 12 weeks in study 2 ( p increase in mean serum 25(OH)D at 6 , 12 , and 24 weeks was observed but no patients achieved a serum 25(OH)D concentration ⩾50 nmol/L. PTH remained elevated in 42 % of patients with secondary hyperparathyroidism at 12 weeks . In study 2 , 100 % and 89 % of patients had serum 25(OH)D>50 nmol/L at 6 and 12 weeks , respectively . All patients with elevated baseline PTH were fully suppressed at 12 weeks . No cases of hypercalcaemia were observed in either group . Conclusion : The 300 000‐IU bolus of vitamin D2 or D3 was practical , well tolerated , and safe . Vitamin D3 had greater potency than equimolar vitamin D2 , with a higher , sustained serum 25(OH)D response and efficacious PTH suppression . To adequately treat vitamin D insufficiency we would recommend administering 300 000 IU oral vitamin D3 approximately three times per year", "Few year-long vitamin D supplementation trials exist that match seasonal changes . The aim of this study was to determine whether daily oral vitamin D3 at 400 IU or 1000 IU compared with placebo affects annual bone mineral density ( BMD ) change in postmenopausal women in a 1-year double-blind placebo controlled trial in Scotl and . White women aged 60 to 70 years ( n = 305 ) were r and omized to one of two doses of vitamin D or placebo . All participants started simultaneously in January/February 2009 , attending visits at bimonthly intervals with 265 ( 87 % ) women attending the final visit and an additional visit 1 month after treatment cessation . BMD ( Lunar iDXA ) and 1,25-dihydroxyvitamin D[1,25(OH)2 D ] , N-terminal propeptide of type 1 collagen [ P1NP ] , C-terminal telopeptide of type I collagen [ CTX ] , and fibroblast growth factor-23 [ FGF23 ] were measured by immunoassay at the start and end of treatment . Circulating PTH , serum Ca , and total 25-hydroxyvitamin D [ 25(OH)D ] ( latter by t and em mass spectrometry ) were measured at each visit . Mean BMD loss at the hip was significantly less for the 1000 IU vitamin D group ( 0.05 % ± 1.46 % ) compared with the 400 IU vitamin D or placebo groups ( 0.57 % ± 1.33 % and 0.60 % ± 1.67 % , respectively ) ( p 0.05 ) . Mean ( ± SD ) baseline 25(OH)D was 33.8 ± 14.6 nmol/L ; comparative 25(OH)D change for the placebo , 400 IU , and 1000 IU vitamin D groups was -4.1 ± 11.5 nmol/L , + 31.6 ± 19.8 nmol/L , and + 42.6 ± 18.9 nmol/L , respectively . Treatment did not change markers of bone metabolism , except for a small reduction in PTH and an increase in serum calcium ( latter with 1000 IU dose only ) . The discordance between the incremental increase in 25(OH)D between the 400 IU and 1000 IU vitamin D and effect on BMD suggests that 25(OH)D may not accurately reflect clinical outcome , nor how much vitamin D is being stored", "There are few data on the relative effects of calcium supplementation with or without extra vitamin D on BMD in patients selected for low vitamin D status . The aim of this study is to evaluate the relative importance of vitamin D and calcium treatment on BMD and bone-related chemistry in elderly women with vitamin D insufficiency . Three hundred two elderly women ( age , 77.2 + /- 4.6 yr ) with serum 25(OH)D concentrations in a 1-yr r and omized , double-blind , placebo-controlled trial . All subjects received 1000 mg calcium citrate per day with either 1000 IU ergocalciferol ( vitamin D(2 ) ) or identical placebo ( control ) . The effects of time and time treatment interactions were evaluated by repeated- measures ANOVA . At baseline , calcium intake was 1100 mg/d , and 25(OH)D was 44.3 + /- 12.9 nM ; this increased in the vitamin D group by 34 % but not the control group after 1 year ( 59.8 + /- 13.8 versus 45.0 + /- 13.3 nM , p Total hip and total body BMD increased significantly , and procollagen type I intact N-terminal propeptide ( PINP ) decreased during the study with no difference between the treatment groups ( hip BMD change : vitamin D , + 0.5 % ; control , + 0.2 % ; total body BMD change : vitamin D , + 0.4 % ; control , + 0.4 % ; PINP change : vitamin D , -3.9 % ; placebo , -2.8 % ) . Although the fasting plasma and urine calcium increased in both groups equally , there was no detectable change in serum PTH . The increase in 25(OH)D achieved with vitamin D supplementation had no extra effect on active fractional intestinal calcium absorption , which fell equally in both groups ( vitamin D , -17.4 % ; control , -14.8 % ) . In patients with a baseline calcium intake of 1100 mg/d and vitamin D insufficiency , vitamin D(2 ) 1000 IU for 1 year has no extra beneficial effect on bone structure , bone formation markers , or intestinal calcium absorption over an additional 1000 mg of calcium . Vitamin D supplementation adds no extra short-term skeletal benefit to calcium citrate supplementation even in women with vitamin D insufficiency", "Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as \" mortality , \" \" other objective , \" \" or subjective , \" and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes", "BACKGROUND The Women 's Health Initiative ( WHI ) r and omized clinical trial ( RCT ) of calcium plus vitamin D ( CaD ) supplements found a 17 % excess in urinary tract stone incidence in the supplemented group . This study evaluated whether this risk is modified by participant characteristics . OBJECTIVE We examined the correlates of urinary tract stone occurrence in the CaD arm of the WHI trial . DESIGN We analyzed an RCT involving 36,282 postmenopausal women aged 50 - 79 y from 40 WHI centers : 18,176 women received 500 mg calcium carbonate plus 200 IU vitamin D(3 ) twice daily ( 1000 mg and 400 IU daily , respectively ) , and 18,106 women received a matching placebo for an average of 7.0 y. The incidence of urinary tract stones was determined . RESULTS The incidence of self-reported clinical ly diagnosed urinary tract stones was more common in the active CaD medication group than in the placebo group ( hazard ratio : 1.17 ; 95 % CI : 1.02 , 1.34 ) : 449 women in the CaD group and 381 women in the placebo group reported a stone during the trial . The rates of self-reported stones did not differ between various demographic , anthropomorphic , dietary , and other hypothesized risk factors according to r and omization assignment . Neither the total calcium intake nor the use of calcium supplements at baseline was associated with the risk of stones . In sensitivity analyses that censored participants who were below 80 % adherence , the findings were similar . CONCLUSIONS Daily supplementation with CaD for 7 y was associated with an increase in the number of self-reported urinary tract stones . These findings have implication s for CaD supplement use . This trial was registered with the WHI at clinical trials.gov as NCT00000611" ]	41189a46-06ff-11f0-808a-c43d1ab1c353
The aim was to evaluate the efficacy of various types of lasers used as an adjunct to chemo-mechanical disinfection of infected root canals with the outcome measures ' normal periapical condition ' or ' reduction of microbial load ' . PubMed , CENTRAL and ISI Web of Knowledge literature search es with specific indexing terms and a subsequent h and search were made with stated limits and criteria . Relevant publications were retrieved , followed by interpretation . The quality of each included publication was assessed as high , moderate or low . The initial search process yielded 234 publications . All abstract s of these publications were read , and the reference lists of relevant publications were h and - search ed . Ten articles were read in full text and interpreted according to a data extraction form . Five were included in the systematic review and were assessed . A meta- analysis was impossible to perform because the included studies were heterogeneous with regard to study design , treatment and outcome measures . Positive effects were reported ; however , no concluding evidence grade could be made because each included study was judged to have low quality , primarily due to lack of a power analysis , blinding and reproducibility . The evidence grade for whether lasers can be recommended as an adjunct to chemo-mechanical disinfection of infected root canals was insufficient . This does not necessarily imply that laser should not be used as an adjunct to root canal treatment but instead underscores the need for future high- quality studies	[ "INTRODUCTION This study reports the antimicrobial effect of photodynamic therapy ( PDT ) combined with endodontic treatment in patients with necrotic pulp infected with microflora resistant to a previous antibiotic therapy . METHODS Thirty anterior teeth from 21 patients with periapical lesions that had been treated with conventional endodontic treatment and antibiotic therapy were selected . Microbiological sample s were taken ( 1 ) after accessing the root canal , ( 2 ) after endodontic therapy , and ( 3 ) after PDT . RESULTS All the patients had at least 1 microorganism resistant to antibiotics . PDT used polyethylenimine chlorin(e6 ) as a photosensitizer and a diode laser as a light source ( P = 40 mW , t = 4 minutes , E = 9.6 J ) . Endodontic therapy alone produced a significant reduction in numbers of microbial species but only 3 teeth were free of bacteria , whereas the combination of endodontic therapy with PDT eliminated all drug-resistant species and all teeth were bacteria-free . CONCLUSIONS The use of PDT added to conventional endodontic treatment leads to a further major reduction of microbial load . PDT is an efficient treatment to kill multi-drug resistant microorganisms ", "Previous papers in this series on evidence -based dentistry have discussed the first 2 steps in seeking answers to clinical problems formulating a clear question and strategically search ing for evidence . The next step , critical appraisal of the evidence , is made easier if one underst and s the basic concepts of clinical research design . The strongest design , especially for questions related to therapeutic or preventive interventions , is the r and omized , controlled trial . Questions relating to diagnosis , prognosis and causation are often studied with observational , rather than experimental , research design s. The strongest study design should be used whenever possible . Rules have been established to grade research evidence . This paper , the fourth in the series , presents an overview of research methodology most commonly used in the dental literature", "Objective To determine the microbiological effect of photoactivated disinfection ( PAD ) as an adjunct to normal root canal disinfection in vivo . Design A r and omised trial carried out in general dental practice .Subjects and methods Patients presenting with symptoms of irreversible pulpitis or periradicular periodontitis requiring endodontic therapy were selected at r and om . A microbiological sample of the canal was taken on accessing the canal , after conventional endodontic therapy , and finally after the PAD process ( photosensitiser and light ) had been carried out on the prepared canal . All three sample s from each canal were plated within 30 minutes of sampling and cultured anaerobically for five days . Growth of viable bacteria was recorded for each sample to determine bacterial load . Results Thirty of the 32 canals were included in the results . Cultures from the remaining two did not reach the laboratory within the target time during which viability was sustained . Of the remaining 30 , 10 canals were negative to culture . These were either one of the canals in multi rooted teeth where the others were infected or where a pre-treatment with a poly-antibiotic paste had been applied to hyperaemic vital tissue . Sixteen of the remainder were negative to culture after conventional endodontic therapy . Three of the four which had remained infected cultured negative after the PAD process . In the one canal where culturable bacteria were still present , a review of the light delivery system showed a fracture in the fibre reducing the effective light output by 90 % . Conclusions The PAD system offers a means of destroying bacteria remaining after using conventional irrigants in endodontic therapy", " Forty-four teeth in 38 patients , diagnosed with chronic apical periodontitis , were endodontically treated . Root canals were shaped using a step-back technique with 5 % NaOCl and 3 % H2O2 as irrigants . In half of the teeth the canal terminus was irradiated with pulsed Nd : YAG laser ( 1 W , 15 pps , 1 s ) . All canals were then obturated with laterally condensed gutta-percha points and sealer , and final radiographs were obtained . Occurrence of spontaneous pain was recorded 1 day after treatment . Percussion pain was recorded after 1 week , and then at 3 and 6 months after treatment . Radiographic follow-up was performed at 3 and 6 months . Percussion pain was significantly less ( P pulsed Nd : YAG laser might be advantageous for the treatment of infected root canals" ]	41189a82-06ff-11f0-808a-c43d1ab1c353
Nutritional supplements can influence outcomes for individuals undergoing major surgery , particularly in older persons whose functional reserve is limited . Accelerating recovery from total hip replacement ( THR ) and total knee replacement ( TKR ) may offer significant benefits . Therefore , we explored the role of nutritional supplements in improving recovery following THR and TKR . A systematic review was conducted to source r and omized clinical trials that tested nutritional supplements in cohorts of THR or TKR patients . Our search yielded nine relevant trials . Intake of a carbohydrate-containing fluid is reported to improve insulin-like growth factor levels , reduce hunger , nausea , and length of stay , and attenuate the decrease in whole-body insulin sensitivity and endogenous glucose release . Amino acid supplementation is reported to reduce muscle atrophy and accelerate return of functional mobility . One paper reported a suppressive effect of beta-hydroxy beta-methylbutyrate , L-arginine , and L-glutamine supplementation on muscle strength loss following TKR . There is limited evidence for nutritional supplementation in THR and TKR pathways ; however , the low risk profile and potential benefits to adjunctive treatment methods , such as exercise programs , suggest nutritional supplements may have a role . Optimizing nutritional status pre-operatively may help manage the surgical stress response , with a particular benefit for undernourished , frail , or elderly individuals	[ "Context Perioperative oral carbohydrate intake is beneficial to general surgery patients . Total hip arthroplasty is a common surgical procedure , and even a moderate improvement in patient outcome could have a significant effect on the re sources needed for these patients . However , few studies have focused on the effects of carbohydrate intake on orthopaedic patients . Objective The purpose of this study was to investigate if perioperative oral carbohydrate intake alters the postoperative course for patients undergoing total hip arthroplasty . The primary hypothesis was that pain scores would be lower in patients treated with carbohydrate . Design A r and omised , double-blind , controlled trial . Setting This study was carried out between September 2009 and April 2011 at a district Swedish hospital that specialises in orthopaedic surgery . Patients Sixty ASA physical status I – III patients scheduled for elective total hip arthroplasty were included . Exclusion criteria were obesity , diabetes , prior hip surgery to the same hip , ongoing infection , immunological deficiency or age less than 50 or more than 80 years . Interventions Patients were given 400 ml of either an oral 12.5 % carbohydrate solution or a placebo beverage ( flavoured water ) 1.5 h before and 2 h after surgery . Main outcome measures Visual analogue scales were used to score six discomfort parameters . Results Immediately prior to surgery , the carbohydrate-treated patients were less hungry ( median score 9.5 vs. 22 mm ) and experienced less nausea ( 0 vs. 1.5 mm ) ( P less pain at 12 , 16 and 20 h ( median scores 20 , 30 and 34 vs. 7 , 5 and 0 mm ; P oral carbohydatre prior to total hip arthroplasty", "Postoperative insulin resistance is a well-characterized metabolic state that has been shown to correlate with the length of postoperative stay in hospital . Preoperative intravenous or oral carbohydrate treatment has been shown to attenuate the development of postoperative insulin resistance measured 1 day after surgery . To study the effects of preoperative oral carbohydrate treatment on postoperative changes in insulin resistance and substrate utilization , in the absence of postoperative confounding factors , 15 patients were double-blindly treated with either a carbohydrate-rich beverage ( 12.5 % ) ( n = 8) or placebo ( n = 7 ) before undergoing total hip replacement surgery . Insulin sensitivity , endogenous glucose release , and substrate oxidation rates were measured before and immediately after surgery . Whole body insulin sensitivity decreased by 18 % in the treatment group vs. 43 % in the placebo group ( P insulin-induced nonoxidative glucose disposal after surgery . The better preservation of insulin sensitivity in the treatment group was attributable to a less reduced glucose disposal in peripheral tissues and increased glucose oxidation rates", "Background Surgery induces insulin resistance that might be alleviated by a nutritional drink given preoperatively . The authors hypothesized that some of the beneficial effects of the drink could be attributed to the volume component ( approximately 1 L ) rather than to the nutrients . Methods Sixty patients scheduled for elective total hip replacement under spinal anesthesia were recruited to a clinical trial , and r and omly allocated to preoperative fasting , to oral ingestion of tap water , or to oral ingestion of a carbohydrate drink . An intravenous glucose tolerance test calculated glucose clearance and insulin sensitivity on the day before surgery , in the postoperative ward , and on the day after surgery . Other parameters were stress ( cortisol in plasma and urine ) , muscle catabolism ( urinary 3-methylhistidine ) , and wellbeing . Results Fifty-seven patients completed the study . In the postoperative ward , the glucose clearance and the insulin response had decreased from the previous day by 23 % and 36 % , respectively . Insulin sensitivity did not decrease until the next morning ( −48 % ) and was due to an increased insulin response ( + 51 % ) . Cortisol excretion was highest on the day of surgery , while 3-methylhistidine increased 1 day later . Follow-up on the third postoperative day showed an average of 1.5 complications per patient . Wellbeing was better 2 weeks after than before the surgery . None of the measured parameters differed significantly between the study groups . Conclusions Preoperative ingestion of tap water or a nutritional drink had no statistically significant effect on glucose clearance , insulin sensitivity , postoperative complications , or wellbeing in patients undergoing elective hip surgery . Trial registration Registration number : NCT 01211184 ( http://www . clinical trials.gov", "Background Multimodal protocol s of perioperative care may enhance postoperative recovery . However , limited information is available on preoperative immune and carbohydrate (CHO)-enriched drinks in patients undergoing hip arthroplasty . We aim ed to investigate the effect of a multimodal protocol ( ACERTO protocol ) plus preoperative immune nutrition on the length of stay ( LOS ) and the postoperative acute phase response of patients undergoing total hip arthroplasty . Methods Thirty-two patients ( mean age , 58 years ; range , 26–85 years ; 16 males ) were r and omized to receive either the ACERTO protocol ( n = 15 , ACERTO Group ) , which consisted of 6 h preoperative fasting for solids , an oral drink ( 200 mL of 12.5 % maltodextrin ) up to 2 h before induction of anesthesia , restricted intravenous fluids ( only 1000 mL of crystalloid fluid after surgery ) and preoperative immune nutrition ( 600 mL/day of Impact - Nestlé , Brazil ) for five days prior to surgery , or traditional care ( n = 17 ; control group ) , which consisted of 6–8 h preoperative fasting , intravenous hydration until the 1st postoperative day and no preoperative immune supplementation . The main endpoint was LOS . C-reactive protein ( CRP ) was the secondary endpoint and was assessed during induction of anesthesia and on postoperative day 2 . Results Neither deaths nor postoperative complications occurred . The median LOS was 3 ( 2–5 ) days in the ACERTO group and 6 ( 3–8 ) days in controls ( P . Postoperative CRP was higher in the control group ( P The ACERTO multimodal protocol of perioperative care plus preoperative immune nutrition may decrease LOS and postoperative CRP levels in total hip arthroplasty . Trial registration Clinical Trials :", "BACKGROUND By the year 2030 , 3.48 million older U.S. adults are projected to undergo total knee arthroplasty ( TKA ) . Following this surgery , considerable muscle atrophy occurs , result ing in decreased strength and impaired functional mobility . Essential amino acids ( EAAs ) have been shown to attenuate muscle loss during periods of reduced activity and may be beneficial for TKA patients . METHODS We used a double-blind , placebo-controlled , r and omized clinical trial with 28 older adults undergoing TKA . Patients were r and omized to ingest either 20 g of EAAs ( n = 16 ) or placebo ( n = 12 ) twice daily between meals for 1 week before and 2 weeks after TKA . At baseline , 2 weeks , and 6 weeks after TKA , an MRI was performed to determine mid-thigh muscle and adipose tissue volume . Muscle strength and functional mobility were also measured at these times . RESULTS TKA patients receiving placebo exhibited greater quadriceps muscle atrophy , with a -14.3 ± 3.6 % change from baseline to 2 weeks after surgery compared with -3.4 ± 3.1 % for the EAA group ( F = 5.16 , P = 0.036 ) and a -18.4 ± 2.3 % change from baseline to 6 weeks after surgery for placebo versus -6.2 ± 2.2 % for the EAA group ( F = 14.14 , P = 0.001 ) . EAAs also attenuated atrophy in the nonoperated quadriceps and in the hamstring and adductor muscles of both extremities . The EAA group performed better at 2 and 6 weeks after surgery on functional mobility tests ( all P 0.05 ) . Change in quadriceps muscle atrophy was significantly associated with change in functional mobility ( F = 5.78 , P = 0.021 ) . CONCLUSION EAA treatment attenuated muscle atrophy and accelerated the return of functional mobility in older adults following TKA . TRIAL REGISTRATION Clinical trials.gov NCT00760383", "OBJECTIVES Total knee arthroplasty ( TKA ) performed in knee osteoarthritis patients is reported to be immediately followed by a decrease in quadriceps muscle strength . We investigated the effects of supplementation with a combination β-hydroxy-β-methyl butyrate , L-arginine , and L-glutamine ( HMB/Arg/Gln ) on the postoperative recovery of quadriceps muscle strength in patients after TKA . METHODS Study subjects were 23 patients ( 12 women ; mean age : 70.5 ) who underwent TKA . The patients were r and omly allocated into the control group or the group that consumed HMB/Arg/Gln supplementation ( HMB/Arg/Gln group ) . HMB/Arg/Gln supplementation or control food were consumed for 5 days before the surgery and for 28 days after the surgery , and maximal quadriceps strength was measured at 7 days before the surgery , and at 14 , 28 and 42 days after the surgery . During the study , total energy expenditure was measured using a lifestyle recording device . The two groups followed the rehabilitation in the same way . RESULTS The maximal quadriceps strength was 1.1±0.62 Nm/Kg before surgery and 0.7±0.9 Nm/Kg after surgery 14 days in the control group ( p=0.02 ) , and 1.1±0.3 Nm/Kg before surgery and 0.9±0.4 Nm/Kg after surgery 14 days in the HMB/Arg/Gln group . Although the control group experienced a significant loss of muscle strength after the surgery , the HMB/Arg/Gln group did not . There was no significant difference in total energy expenditure between the two groups . CONCLUSIONS Consuming HMB/Arg/Gln supplementation may suppress the loss of muscle strength after TKA . Intervention with exercise and nutrition appears to enable patients to maintain their quadriceps strength", "UNLABELLED Infusions of carbohydrates before surgery have been shown to reduce postoperative insulin resistance . Presently , we investigated the effects of a carbohydrate drink , given shortly before surgery , on postoperative insulin sensitivity . METHODS Insulin sensitivity and glucose turnover ( [ 6 , 6,(2)H(2)]-D-glucose ) were measured using hyper-insulinemic , normoglycemic clamps before and after elective surgery . Sixteen patients undergoing total hip replacement were r and omly assigned to preoperative oral carbohydrate administration ( CHO-H , n = 8) or the same amount of a placebo drink ( placebo , n = 8) before surgery . Insulin sensitivity was measured before and immediately after surgery . Patients undergoing elective colorectal surgery were studied before surgery and 24 h postoperatively ( CHO-C ( n = 7 ) , and fasted ( n = 7 ) , groups ) . The fasted group underwent surgery after an overnight fast . In both studies , the CHO groups received 800 ml of an isoosmolar carbohydrate rich beverage the evening before the operation ( 100 g carbohydrates ) , as well as another 400 ml ( 50 g carbohydrates ) 2 h before the initiation of anesthesia . RESULTS Immediately after surgery , insulin sensitivity was reduced 37 % in the placebo group ( P CHO-H group ( -16 % , p = NS ) . During clamps performed 24h postoperatively , insulin sensitivity and whole-body glucose disposal was reduced in both groups , but the reduction was greater compared to that in the CHO-C group ( -49 + /- 6 % vs. -26 + /- 8 % , P > > 0.05 fasted vs. CHO-C ) . CONCLUSIONS Patients given a carbohydrate drink shortly before elective surgery displayed less reduced insulin sensitivity after surgery as compared to patients undergoing surgery after an overnight fast", "BACKGROUND & AIMS Postoperative metabolism is characterised by insulin resistance and a negative whole-body nitrogen balance . Preoperative carbohydrate treatment reduces insulin resistance in the first day after surgery . We hypothesised that preoperative oral carbohydrate treatment attenuates insulin resistance and improves whole-body nitrogen balance 3 days after surgery . METHODS Fourteen patients undergoing total hip replacement were double-blindly r and omised to preoperative oral carbohydrate treatment ( 12.5 % , 800 + 400 ml , n = 8) or placebo ( n = 6 ) . Glucose kinetics ( 6,6-D2-glucose ) , substrate utilisation ( indirect calorimetry ) and insulin sensitivity ( hyperinsulinaemic-euglycaemic clamp ) were measured preoperatively and on the third day after surgery . Nitrogen losses were monitored for 3 days after surgery . Values are mean ( SEM ) . Analysis of variance ( ANOVA ) statistics were used . RESULTS Endogenous glucose release during insulin infusion increased after surgery in the placebo group . Preoperative carbohydrate treatment , as compared to placebo , significantly attenuated postoperative endogenous glucose release ( 0.69 ( 0.07 ) vs. 1.21 (0.13)mg kg(-1 ) x min(-1 ) , P whole-body glucose disposal and nitrogen balance were similar between groups . CONCLUSIONS While insulin resistance in the first day after surgery has previously been characterised by reduced glucose disposal , enhanced endogenous glucose release was the main component of postoperative insulin resistance on the third postoperative day . Preoperative carbohydrate treatment attenuated endogenous glucose release on the third postoperative day", "Background and aims : In response to surgical stress , the body reacts with a change in metabolism to a catabolic state . This is further aggravated by the fasting state preoperatively . We aim ed to determine the effects on catabolism i.e. , body composition and IGF-I bioavailability as measured by the serum IGF-I/IGFBP-1 ratio , of a carbohydrate rich drink given shortly before surgery . Methods : Twenty-nine patients scheduled for a total hip replacement ( THR ) were r and omized in a double-blind placebo-controlled pilot study to a carbohydrate-rich drink or to placebo pre-operatively . The nutritional supplementation consisted of an iso-osmolar carbohydrate-rich drink ( 12.5 g carbohydrates/100 ml , pH 5.0 ) . Fasting blood sample s were collected before surgery and repeated after 5 days and after 2 months . IGF-I and IGFBP-1 were determined in serum by RIA . Body composition was determined by dual energy X-ray absorptiometry ( DXA ) . Results : Compared with placebo we found a relative increase in IGF-I bioavailability post-operatively after a carbohydrate-rich drink given shortly before surgery . There were no significant long-term differences in the changes in fat or lean body mass between groups , but , in a subgroup with late scheduled surgery , there was a tendency to a difference ( p=0.08 ) of fat loss after 2 months , with less fat loss in those who received another carbohydrate drink close to surgery . The pre-operative intake of a 200–200x2 ml carbohydrate drink was well tolerated and safe . There were no adverse events such as pulmonary aspiration before , during or after operation . Conclusions : A carbohydrate-rich drink given shortly before surgery increases IGF-I bioavailability post-operatively in patients undergoing a THR , but has no significant effects on body composition after 2 months in physically active people . We suggest that , if the operation is postponed for more than four hours on the same day , an additional carbohydrate drink should be given", "Protein and other compounds can exert anabolic effects on skeletal muscle , particularly in conjunction with exercise . The objective of this study was to evaluate the efficacy of twice daily consumption of a protein-based , multi-ingredient nutritional supplement to increase strength and lean mass independent of , and in combination with , exercise in healthy older men . Forty-nine healthy older men ( age : 73 ± 1 years [ mean ± SEM ] ; BMI : 28.5 ± 1.5 kg/m2 ) were r and omly allocated to 20 weeks of twice daily consumption of either a nutritional supplement ( SUPP ; n = 25 ; 30 g whey protein , 2.5 g creatine , 500 IU vitamin D , 400 mg calcium , and 1500 mg n-3 PUFA with 700 mg as eicosapentanoic acid and 445 mg as docosahexanoic acid ) ; or a control ( n = 24 ; CON ; 22 g of maltodextrin ) . The study had two phases . Phase 1 was 6 weeks of SUPP or CON alone . Phase 2 was a 12 week continuation of the SUPP/CON but in combination with exercise : SUPP + EX or CON + EX . Isotonic strength ( one repetition maximum [ 1RM ] ) and lean body mass ( LBM ) were the primary outcomes . In Phase 1 only the SUPP group gained strength ( Σ1RM , SUPP : + 14 ± 4 kg , CON : + 3 ± 2 kg , P ) and lean mass ( LBM , + 1.2 ± 0.3 kg , CON : -0.1 ± 0.2 kg , P gained strength during Phase 2 , upon completion of the study upper body strength was greater in the SUPP group compared to the CON group ( Σ upper body 1RM : 119 ± 4 vs. 109 ± 5 kg , P = 0.039 ) . We conclude that twice daily consumption of a multi-ingredient nutritional supplement increased muscle strength and lean mass in older men . Increases in strength were enhanced further with exercise training . Trial Registration : Clinical Trials.gov", "BACKGROUND Loss of muscle mass due to prolonged bed rest decreases functional capacity and increases hospital morbidity and mortality in older adults . OBJECTIVE To determine if HMB , a leucine metabolite , is capable of attenuating muscle decline in healthy older adults during complete bed rest . DESIGN A r and omized , controlled , double-blinded , parallel-group design study was carried out in 24 healthy ( SPPB ≥ 9 ) older adult subjects ( 20 women , 4 men ) , confined to complete bed rest for ten days , followed by resistance training rehabilitation for eight weeks . Subjects in the experimental group were treated with HMB ( calcium salt , 1.5 g twice daily - total 3 g/day ) . Control subjects were treated with an inactive placebo powder . Treatments were provided starting 5 days prior to bed rest till the end rehabilitation phase . DXA was used to measure body composition . RESULTS Nineteen eligible older adults ( BMI : 21 - 33 ; age : 60 - 76 year ) were evaluable at the end of the bed rest period ( Control n = 8 ; Ca-HMB n = 11 ) . Bed rest caused a significant decrease in total lean body mass ( LBM ) ( 2.05 ± 0.66 kg ; p = 0.02 , paired t-test ) in the Control group . With the exclusion of one subject , treatment with HMB prevented the decline in LBM over bed rest -0.17 ± 0.19 kg ; p = 0.23 , paired t-test ) . There was a statistically significant difference between treatment groups for change in LBM over bed rest ( p = 0.02 , ANOVA ) . Sub- analysis on female subjects ( Control = 7 , HMB = 8) also revealed a significant difference in change in LBM over bed rest between treatment groups ( p = 0.04 , ANOVA ) . However , differences in function parameters could not be observed , probably due to the sample size of the study . CONCLUSIONS In healthy older adults , HMB supplementation preserves muscle mass during 10 days of bed rest . These results need to be confirmed in a larger trial", " Preoperative oral carbohydrate ( CHO ) reduces postoperative insulin resistance . In this r and omized trial , the effect of CHO on postoperative whole‐body protein turnover was studied" ]	41189abe-06ff-11f0-808a-c43d1ab1c353
Background Roux-en-Y gastric bypass ( RYGB ) is considered effective for weight loss and for treatment of many obesity-related metabolic diseases . Ghrelin is an essential orexigenic peptide that plays an indispensable role in controlling body weight and energy homeostasis of post-operative patients . This systematic review and meta- analysis aim ed to investigate changes in the level of fasting total ghrelin following RYGB . Methods A systematic literature search of PubMed , EMBASE , and the Cochrane Library until April 2018 with keywords “ ghrelin ” and “ gastric bypass ” was performed in accordance with the MOOSE guidelines and PRISMA statement . Three review ers independently selected the studies and extracted data . Quality assessment of the included studies was undergone . A r and om effects model was employed to calculate overall effect sizes . Subgroup analyses and meta-regression were subsequently performed . Results Sixteen studies with 325 patients were included . We found ghrelin levels had an increasing tendency ( SMD = 0.30 ; 95 % CI = 0.04 to 0.57 ) despite moderate heterogeneity ( I2 = 58 % ) . Subsequent subgroup analysis indicated that ghrelin levels decreased ( SMD = − 0.49 ; 95 % CI = − 0.98 to 0.00 ) in the short term ( ≤ 3 months ) and increased ( SMD = 0.46 ; 95 % CI = 0.22 to 0.69 ) in the long term ( > 3 months ) after RYGB . Meta-regression showed that gastric pouch volume , alimentary limb length and biliopancreatic limb length were not associated with changes in ghrelin levels . Conclusion Fasting total ghrelin levels decreased in the short term ( ≤ 3 months ) and increased in the long term ( > 3 months ) after RYGB	[ "Objective : To examine the effect of an equivalent weight loss , by gastric bypass surgery ( GBP ) or by diet , on peptide YY3–36 ( PYY3–36 ) , ghrelin , and leptin levels and to determine the effect of diabetes status on PYY3–36 levels . Summary Background Data : The increased PYY3–36 levels after GBP may be involved in the magnitude and the sustainability of weight loss after surgery . Methods : Of the 30 morbidly obese women who participated in the study , 21 had type 2 diabetes mellitus , and were studied before and after equivalent weight loss of 10 kg by either GBP ( n = 11 ) or by diet ( n = 10 ) . Results : PYY3–36 levels were higher in obese diabetic as compared with nondiabetic individuals ( 64.1 ± 34.4 pg/mL vs. 39.9 ± 21.1 pg/mL ; P ) . PYY3–36 levels increased markedly in response to oral glucose after GBP ( peak : 72.3 ± 20.5 pg/mL–132.7 ± 49.7 pg/mL ; P P = NS ) . Fasting ghrelin levels increased after diet ( 425 ± 91 pg/mL–519 ± 105 pg/mL ; P GBP , but not diet-induced weight loss , result ed in markedly increased glucose-stimulated PYY3–36 levels . The increase in stimulated PYY3–36 levels after GBP is likely a result of the surgery rather than a secondary outcome of weight loss . Changes in PYY3–36 levels and ghrelin could contribute to the success of GBP in sustaining weight loss", "Objective : To present long-term results of a large series of patients su bmi tted to laparoscopic Roux-en-Y gastric bypass ( RYGBP ) for morbid obesity . Background : Reports on long-term results of RYGBP are scarce and focus primarily on weight loss . Our aim is to provide mid- to long-term data of RYGBP , with detailed results on weight loss , evolution of comorbidities and quality of life , also using the BAROS score . Methods : All patients who underwent a primary RYGBP for morbid obesity in our 2 hospitals between 1999 and August 2008 were included . Data were collected prospect ively in a computerized data base , and review ed for the purpose of this study . Results : A total of 379 patients were included in the analysis of long-term results , 282 women , and 97 men , with a mean BMI of 46.3 kg/m2 . After 5 years , 74.9 % of the patients achieved an excess weight loss of at least 50 % , with a mean of 62.7 % and 76.8 % achieved a BMI long-term weight regain . All comorbidities improved markedly in the vast majority of patients , with no significant difference between the 3- and 5-year terms . Quality of life also improved markedly , and more than 95 % of the patients had a good to excellent 5-year overall result according to the BAROS score . Conclusions : Laparoscopic RYGBP for morbid obesity results in good and maintained weight loss up to 7 years in the majority of patients , improves quality of life and markedly improves all the evaluated comorbidities , result ing in good to excellent overall 5-year results in 97 % of the patients according to the BAROS score", "Background : Bariatric surgery is currently the most effective treatment in morbidly obese patients , leading to durable weight loss . Objective : In this prospect i ve double blind study , we aim to evaluate and compare the effects of laparoscopic Roux-en-Y gastric bypass ( LRYGBP ) with laparoscopic sleeve gastrectomy ( LSG ) on body weight , appetite , fasting , and postpr and ial ghrelin and peptide-YY ( PYY ) levels . Methods : After r and omization , 16 patients were assigned to LRYGBP and 16 patients to LSG . Patients were reevaluated on the 1st , 3rd , 6th , and 12th postoperative month . Blood sample s were collected after an overnight fast and in 6 patients in each group after a st and ard 420 kcal mixed meal . Results : Body weight and body mass index ( BMI ) decreased markedly ( P Excess weight loss was greater after LSG at 6 months ( 55.5 % ± 7.6 % vs. 50.2 % ± 6.5 % , P = 0.04 ) and 12 months ( 69.7 % ± 14.6 % vs. 60.5 % ± 10.7 % , [ P = 0.05 ] ) . After LRYGBP fasting ghrelin levels did not change significantly compared with baseline ( P = 0.19 ) and did not decrease significantly after the test meal . On the other h and , LSG was followed by a marked reduction in fasting ghrelin levels ( P . Fasting PYY levels increased after either surgical procedure ( P ≤ 0.001 ) . Appetite decreased in both groups but to a greater extend after LSG . Conclusion : PYY levels increased similarly after either procedure . The markedly reduced ghrelin levels in addition to increased PYY levels after LSG , are associated with greater appetite suppression and excess weight loss compared with LRYGBP", "Objectives We sought to determine : 1 ) if early weight regain between one and two years after RYGB is associated with worsened hepatic and peripheral insulin sensitivity , and 2 ) if preoperative levels of ghrelin and leptin are associated with early weight regain after RYGB . Design and Methods Hepatic and peripheral insulin sensitivity and ghrelin and leptin plasma levels were assessed longitudinally in 45 subjects before RYGB and at one month , six months , one year , and two years post operatively . Weight regain was defined as ≥ 5 % increase in body weight between one and two years after RYGB . Results Weight regain occurred in 33 % of subjects , with an average increase in body weight of 10 ± 5 % ( 8.5 ± 3.3 kg ) . Weight regain was not associated with worsening of peripheral or hepatic insulin sensitivity . Subjects with weight regain after RYGB had higher preoperative and postoperative levels of ghrelin compared to those who maintained or lost weight during this time . Conversely , the trajectories of leptin levels corresponded with the trajectories of fat mass in both groups . Conclusions Early weight regain after RYGB is not associated with a reversal of improvements in insulin sensitivity . Higher preoperative ghrelin levels might identify patients that are more susceptible to weight regain after RYGB", "Bypass of the foregut following Roux-en-Y gastric bypass ( RYGB ) surgery results in altered nutrient absorption , which is proposed to underlie the improvement in glucose tolerance and insulin sensitivity . We conducted a prospect i ve crossover study in which a mixed meal was delivered orally before RYGB ( gastric ) and both orally ( jejunal ) and by gastrostomy tube ( gastric ) postoperatively ( 1 and 6 wk ) in nine subjects . Glucose , insulin , and incretin responses were measured , and whole-body insulin sensitivity was estimated with the insulin sensitivity index composite . RYGB result ed in an improved glucose , insulin , and glucagon-like peptide-1 ( GLP-1 ) area under the curve ( AUC ) in the first 6 wk postoperatively ( all P ≤ 0.018 ) ; there was no effect of delivery route ( all P ≥ 0.632 ) or route × time interaction ( all P ≥ 0.084 ) . The glucose-dependent insulinotropic polypeptide ( GIP ) AUC was unchanged after RYGB ( P = 0.819 ) ; however , GIP levels peaked earlier after RYGB with jejunal delivery . The ratio of insulin AUC to GLP-1 and GIP AUC decreased after surgery ( P = .001 and 0.061 , respectively ) without an effect of delivery route over time ( both P ≥ 0.646 ) . Insulin sensitivity improved post-RYGB ( P = 0.001 ) with no difference between the gastric and jejunal delivery of the mixed meal over time ( P = 0.819 ) . These data suggest that exclusion of nutrients from the foregut with RYGB does not improve glucose tolerance or insulin sensitivity . However , changes in the foregut response post-RYGB due to lack of nutrient exposure can not be excluded . Our findings suggest that foregut bypass may alter the incretin response by enhanced nutrient delivery to the hindgut", "Ghrelin is a novel endogenous natural lig and for the growth hormone ( GH ) secretagogue receptor that has recently been isolated from the rat stomach . Ghrelin administration stimulates GH secretion but also causes weight gain by increasing food intake and reducing fat utilization in rodents . To investigate the possible involvement of ghrelin in the pathogenesis of human obesity , we measured body composition ( by dual X-ray absorption ) as well as fasting plasma ghrelin concentrations ( radioimmunoassay ) in 15 Caucasians ( 8 men and 7 women , 31+/-9 years of age , 92+/-24 kg body wt , and 29+/-10 % body fat , mean + /- SD ) and 15 Pima Indians ( 8 men and 7 women , 33+/-5 years of age , 97+/-29 kg body wt , and 30+/-8 % body fat ) . Fasting plasma ghrelin was negatively correlated with percent body fat ( r = -0.45 ; P = 0.01 ) , fasting insulin ( r = -0.45 ; P = 0.01 ) and leptin ( r = -0.38 ; P = 0.03 ) concentrations . Plasma ghrelin concentration was decreased in obese Caucasians as compared with lean Caucasians ( P fasting plasma ghrelin was lower in Pima Indians , a population with a very high prevalence of obesity , compared with Caucasians ( 87+/-28 vs. 129+/-34 fmol/ml ; P fasting plasma insulin concentration . There was no correlation between fasting plasma ghrelin and height . Prospect i ve clinical studies are now needed to establish the role of ghrelin in the pathogenesis of human obesity", "The goal of this study was to underst and the mechanisms of greater weight loss by gastric bypass ( GBP ) compared to gastric b and ing ( GB ) surgery . Obese weight- and age-matched subjects were studied before ( T0 ) , after a 12 kg weight loss ( T1 ) by GBP ( n = 11 ) or GB ( n = 9 ) , and at 1 year after surgery ( T2 ) . peptide YY(3 - 36 ) ( PYY(3 - 36 ) ) , ghrelin , glucagon-like peptide-1 ( GLP-1 ) , leptin , and amylin were measured after an oral glucose challenge . At T1 , glucose-stimulated GLP-1 and PYY levels increased significantly after GBP but not GB . Ghrelin levels did not change significantly after either surgery . In spite of equivalent weight loss , leptin and amylin decreased after GBP , but not after GB . At T2 , weight loss was greater after GBP than GB ( P = 0.003 ) . GLP-1 , PYY , and amylin levels did not significantly change from T1 to T2 ; leptin levels continued to decrease after GBP , but not after GB at T2 . Surprisingly , ghrelin area under the curve ( AUC ) increased 1 year after GBP ( P = 0.03 ) . These data show that , at equivalent weight loss , favorable GLP-1 and PYY changes occur after GBP , but not GB , and could explain the difference in weight loss at 1 year . Mechanisms other than weight loss may explain changes of leptin and amylin after GBP", "BACKGROUND Sleeve gastrectomy ( SG ) and Roux-en-Y gastric bypass ( RYGB ) cause weight loss and metabolic improvement , but results of published studies are contradictory . OBJECTIVES The aim of this study was to compare the effects of SG and RYGB on ghrelin , leptin , and glucose homeostasis in a r and omized controlled trial . SETTING University hospital , Pol and . METHODS Seventy-two morbidly obese patients were r and omly selected to undergo either SG ( n = 36 ) or RYGB ( n = 36 ) . Fasting ghrelin , leptin , glucose , insulin , C-peptide , glucagon , glycated hemoglobin , and homeostasis model assessment of insulin resistance were assessed preoperatively and at 1 , 6 , and 12 months postoperatively . No differences were found in anthropometric and biochemical parameters between the study groups at baseline . RESULTS Sixty-nine ( 95.8 % ) patients completed the study . Percentage of excess weight loss at 12 months was 67.6±19.3 % after SG and 64.2±18.5 % after RYGB ( P>.05 ) . Fasting ghrelin levels decreased 1 month after SG ( from 76.8 pmol/L to 35.3 pmol/L ; P 130.2 pmol/L ( P decreased significantly in both groups during 12 months . CONCLUSIONS RYGB and SG induce comparable weight loss and improvement in metabolism of glucose . Ghrelin levels decrease after SG and increase after RYGB , but this difference does not affect similar outcomes of these procedures during 1-year follow-up . The contribution of ghrelin to weight loss or metabolic benefits after bariatric surgery is not straightforward , but rather influenced by multiple factors" ]	41189afa-06ff-11f0-808a-c43d1ab1c353
OBJECTIVE To assess evidence from r and omised clinical trials about the effectiveness of extracts of Boswellia serrata ( frankincense ) . DESIGN Systematic review . DATA SOURCES Electronic search es on Medline , Embase , Cinahl , Amed , and Cochrane Library . H and search es of conference proceedings , bibliographies , and departmental files . REVIEW METHODS All r and omised clinical trials of B serrata extract as a treatment for any human medical condition were included and studies of B serrata preparations combined with other ingredients were excluded . Titles and abstract s of all retrieved articles were read and hard copies of all relevant articles were obtained . Selection of studies , data extraction and validation were done by the author . The Jadad score was used to evaluate the method ological quality of all included trials . RESULTS Of 47 potentially relevant studies , seven met all inclusion criteria ( five placebo controlled , two with active controls ) . The included trials related to asthma , rheumatoid arthritis , Crohn 's disease , osteoarthritis , and collagenous colitis . Results of all trials indicated that B serrata extracts were clinical ly effective . Three studies were of good method ological quality . No serious safety issues were noted . CONCLUSIONS The evidence for the effectiveness of B serrata extracts is encouraging but not compelling	[ "BACKGROUND Flexible sigmoidoscopy ( FS ) has been recommended as a screening method to reduce mortality from colorectal cancer ( CRC ) . The present study evaluates the effect of adding FS to the fecal occult blood test Hemoccult-II ( H-II ) on diagnostic yield of colorectal neoplasia . METHODS A total of 10,978 normal persons aged 50 - 75 years were invited to participate , 5495 persons being allocated at r and om to H-II and FS and 5483 to H-II alone . RESULTS In spite of a lower compliance ( 40 % versus 56 % ) for the combined procedure , the diagnostic yield of colorectal neoplasia was higher than for H-II alone ( 12 CRC versus 4 CRC , and 72 large adenomas versus 14 ) . Within 24 - 62 months after screening there were fewer CRCs detected after H-II + FS than after H-II alone . The stage distribution was less favorable than in screen-detected cases . CONCLUSION One FS may not be an optimal way of screening , but FS deserves to be evaluated in r and omized population studies including repeated H-II tests in the control arm", "Osteoarthritis is a common , chronic , progressive , skeletal , degenerative disorder , which commonly affects the knee joint . Boswellia serrata tree is commonly found in India . The therapeutic value of its gum ( guggulu ) has been known . It posses good anti-inflammatory , anti-arthritic and analgesic activity . A r and omized double blind placebo controlled crossover study was conducted to assess the efficacy , safety and tolerability of Boswellia serrata Extract ( BSE ) in 30 patients of osteoarthritis of knee , 15 each receiving active drug or placebo for eight weeks . After the first intervention , washout was given and then the groups were crossed over to receive the opposite intervention for eight weeks . All patients receiving drug treatment reported decrease in knee pain , increased knee flexion and increased walking distance . The frequency of swelling in the knee joint was decreased . Radiologically there was no change . The observed differences between drug treated and placebo being statistically significant , are clinical ly relevant . BSE was well tolerated by the subjects except for minor gastrointestinal ADRs . BSE is recommended in the patients of osteoarthritis of the knee with possible therapeutic use in other arthritis", "BACKGROUND This r and omised controlled trial is examining the hypothesis that a single flexible sigmoidoscopy screening offered at around age 60 years can lower the incidence and mortality of colorectal cancer . We report here on acceptability , safety , feasibility , and yield . METHODS Men and women aged 55 - 64 years , in 14 UK centres , who responded to a mailed question naire that they would attend for flexible sigmoidoscopy screening if invited , were r and omly assigned screening or control ( ratio one to two ) . The control group was not contacted . Small polyps were removed during screening , and colonoscopy was undertaken if high-risk polyps ( three or more adenomas , size 1 cm or greater , villous , severely dysplastic , or malignant ) were found . FINDINGS Of 354,262 people asked about their interest in having flexible sigmoidoscopy screening , 194,726 ( 55 % ) responded positively , and 170,432 eligible individuals were r and omised . Attendance among those assigned screening was 71 % ( 40,674 of 57,254 ) . 2131 ( 5 % ) were classified as high-risk and referred for colonoscopy ; 38,525 with no polyps or only low-risk polyps detected were discharged . Distal adenomas were detected in 4931 ( 12.1 % ) and distal cancer in 131 ( 0.3 % ) . Proximal adenomas were detected in 386 ( 18.8 % of those undergoing colonoscopy ) and proximal cancer in nine cases ( 0.4 % ) . 62 % of cancers were Dukes ' stage A or locally excised . There was one perforation after flexible sigmoidoscopy and four after colonoscopy . An average of 48 people were screened , and two or three colonoscopy referrals generated , per centre each week . Interpretation Our flexible sigmoidoscopy screening regimen is acceptable , feasible , and safe . The prevalence of neoplasia is high , and colonoscopy referral rates of 5 % are acceptable", "Patients studied here suffered from chronic colitis characterized by vague lower abdominal pain , bleeding per rectum with diarrhoea and palpable tender descending and sigmoid colon . The inflammatory process in colitis is associated with increased formation of leukotrienes causing chemotaxis , chemokinesis , synthesis of superoxide radicals and release of lysosomal enzymes by phagocytes . The key enzyme for leukotriene bio synthesis is 5-lipoxygenase . Boswellic acids were found to be non-redox , non-competitive specific inhibitors of the enzyme 5-lipoxygenase . We studied the gum resin of Boswellia serrata for the treatment of this disease . Thirty patients , 17 males and 13 females in the age range of 18 to 48 years with chronic colitis were included in this study . Twenty patients were given a preparation of the gum resin of Boswellia serrata ( 900 mg daily divided in three doses for 6 weeks ) and ten patients were given sulfasalazine ( 3 gm daily divided in three doses for 6 weeks ) and served as controls . Out of 20 patients treated with Boswellia gum resin 18 patients showed an improvement in one or more of the parameters : including stool properties , histopathology as well as scanning electron microscopy , besides haemoglobin , serum iron , calcium , phosphorus , proteins , total leukocytes and eosinophils . In the control group 6 out of 10 patients showed similar results with the same parameters . Out of 20 patients treated with Boswellia gum resin 14 went into remission while in case of sulfasalazine remission rate was 4 out of 10 . In conclusion , this study shows that a gum resin preparation from Boswellia serrata could be effective in the treatment of chronic colitis with minimal side effects", "Introduction 5-Loxin ® is a novel Boswellia serrata extract enriched with 30 % 3-O-acetyl-11-keto-beta-boswellic acid ( AKBA ) , which exhibits potential anti-inflammatory properties by inhibiting the 5-lipoxygenase enzyme . A 90-day , double-blind , r and omized , placebo-controlled study was conducted to evaluate the efficacy and safety of 5-Loxin ® in the treatment of osteoarthritis ( OA ) of the knee . Methods Seventy-five OA patients were included in the study . The patients received either 100 mg ( n = 25 ) or 250 mg ( n = 25 ) of 5-Loxin ® daily or a placebo ( n = 25 ) for 90 days . Each patient was evaluated for pain and physical functions by using the st and ard tools ( visual analog scale , Lequesne 's Functional Index , and Western Ontario and McMaster Universities Osteoarthritis Index ) at the baseline ( day 0 ) , and at days 7 , 30 , 60 and 90 . Additionally , the cartilage degrading enzyme matrix metalloproteinase-3 was also evaluated in synovial fluid from OA patients . Measurement of a battery of biochemical parameters in serum and haematological parameters , and urine analysis were performed to evaluate the safety of 5-Loxin ® in OA patients . Results Seventy patients completed the study . At the end of the study , both doses of 5-Loxin ® conferred clinical ly and statistically significant improvements in pain scores and physical function scores in OA patients . Interestingly , significant improvements in pain score and functional ability were recorded in the treatment group supplemented with 250 mg 5-Loxin ® as early as 7 days after the start of treatment . Corroborating the improvements in pain scores in treatment groups , we also noted significant reduction in synovial fluid matrix metalloproteinase-3 . In comparison with placebo , the safety parameters were almost unchanged in the treatment groups . Conclusion 5-Loxin ® reduces pain and improves physical functioning significantly in OA patients ; and it is safe for human consumption . 5-Loxin ® may exert its beneficial effects by controlling inflammatory responses through reducing proinflammatory modulators , and it may improve joint health by reducing the enzymatic degradation of cartilage in OA patients .Trail Registration ( Clinical trial registration number : IS RCT N05212803 .", "Background : The ancient Indian ( Asian ) Ayurvedic medicinal system uses herbomineral drugs to treat arthritis . Despite centuries of use , very few have been tested by drug trials . RA-11 ( ARTREX , MENDAR ) , a st and ardized multiplant Ayurvedic drug ( Withania somnifera , Boswellia serrata , Zingiber officinale , and Curcuma longa ) is currently used to treat arthritis . Objective : The objective of this study was to evaluate the efficacy and safety of RA-11 in patients with symptomatic osteoarthritis ( OA ) of the knees . Methods : A total of 358 patients with chronic knee pain were screened free-of-cost in “ arthritis camps ” in an Indian metropolis . Ninety patients with primary OA of the knees ( ACR classification ; Arthritis Rheum 1986;29:1039–1049 ) were found eligible ( postanalgesic washout pain visual analog score [ VAS ] ≥40 mm in either or both knees on body weight-bearing activities ) to enroll into a r and omized , double-blind , placebo-controlled , parallel efficacy , single-center , 32-week drug trial ( 80 % power to detect 25 % difference , P = 0.05 , 2-sided ) . Concurrent analgesics/nonsteroidal antiinflammatory drugs and steroids in any form were not allowed . Lifestyle and /or dietary restrictions , as per routine Ayurveda practice s , were not imposed . Pain VAS ( maximum pain in each knee recorded by the patient during the preceding 48 hours ) and modified WOMAC ( Western Ontario McMaster University OA Index , Likert scale , version 3.0 ) were the primary efficacy variables . The WOMAC section on “ physical function difficulty ” was modified for Indian use and vali date d before the trial . Routine laboratory testing was primarily done to monitor drug safety . At baseline , the groups ( active = 45 , placebo = 45 ) were well matched for several measures ( mean pain VAS : active = 6.17 ; placebo = 6.5 ) . Results :1 ) Efficacy : Compared with placebo , the mean reduction in pain VAS at week 16 ( active = 2.7 , placebo = 1.3 ) and week 32 ( active = 2.8 , placebo = 1.8 ) in the active group was significantly ( P the WOMAC scores at week 16 and week 32 were also significantly superior ( P mild adverse events ( AE ) without any significant difference . 3 ) Withdrawals : Twenty-eight patients were discontinued . None reported drug-related toxicity . The majority failed follow up/compliance . No differences were observed between the groups . Conclusion : This controlled drug trial demonstrates the potential efficacy and safety of RA- 11 in the symptomatic treatment of OA knees over 32 weeks of therapy", "The gum resin of Boswellia serrata , known in Indian Ayurvedic system of medicine as Salai guggal , contains boswellic acids , which have been shown to inhibit leukotriene bio synthesis . In a double-blind , placebo-controlled study forty patients , 23 males and 17 females in the age range of 18 - 75 years having mean duration of illness , bronchial asthma , of 9.58 + /- 6.07 years were treated with a preparation of gum resin of 300 mg thrice daily for a period of 6 weeks . 70 % of patients showed improvement of disease as evident by disappearance of physical symptoms and signs such as dyspnoea , rhonchi , number of attacks , increase in FEV subset1 , FVC and PEFR as well as decrease in eosinophilic count and ESR . In the control group of 40 patients 16 males and 24 females in the age range of 14 - 58 years with mean of 32.95 + /- 12.68 were treated with lactose 300 mg thrice daily for 6 weeks . Only 27 % of patients in the control group showed improvement . The data show a definite role of gum resin of Boswellia serrata in the treatment of bronchial asthma", "BACKGROUND R and omized controlled trials of sufficient power testing the long-term effect of screening for colorectal neoplasia only exist for faecal occult blood testing ( FOBT ) . There is indirect evidence that flexible sigmoidoscopy ( FS ) may have a greater yield . The aim of this study was to determine the diagnostic yield of screening with FS or a combination of FS and FOBT in an average-risk population in an urban and combined urban and rural population in Norway . METHODS 20,780 men and women ( 1:1 ) , aged 50 - 64 years , were invited for once-only screening ( FS only or a combination of FS and FOBT ( 1:1 ) ) by r and omization from the population registry . A positive FS was defined as a finding of any neoplasia or any polyp > or = 10 mm . A positive FS or FOBT qualified for colonoscopy . RESULTS Overall attendance was 65 % . Forty-one ( 0.3 % ) cases of CRC were detected . Any adenoma was found in 2208 ( 17 % ) participants and 545 ( 4.2 % ) had high-risk adenomas . There was no difference in diagnostic yield between the FS and the FS and FOBT group regarding CRC or high-risk adenoma . Work-up load comprised 2821 colonoscopies in 2524 ( 20 % ) screenees and 10 % of screenees were recommended later colonoscopy surveillance . There were no severe complications at FS , but six perforations after therapeutic colonoscopy ( 1:336 ) . CONCLUSIONS The present study bodes well for future management of a national screening programme , provided that follow-up results reflect adequate proof of a net benefit . It is highly question able whether the addition of once-only FOBT to FS will contribute to this effect", "Ulcerative colitis is a chronic inflammatory disease of the colon where leukotrienes are suggested to play an important role for keeping inflammation active . Boswellic acids , the biologically active ingredients of the gum resin of Boswellia serrata ( Sallai guggal ) , have been shown to be specific , nonredox and noncompetitive inhibitors of 5-lipoxygenase , the key enzyme of leukotriene bio synthesis . In patients suffering from ulcerative colitis grade II and III the effect of Boswellia serrata gum resin preparation ( 350 mg thrice daily for 6 weeks ) on stool properties , histolopathology and scan microscopy of rectal biopsies , blood parameters including Hb , serum iron , calcium , phosphorus , proteins , total leukocytes and eosinophils was studied . Patients receiving sulfasalazine ( 1 g thrice daily ) served as controls . All parameters tested improved after treatment with Boswellia serrata gum resin , the results being similar compared to controls : 82 % out of treated patients went into remission ; in case of sulfasalazine remission rate was 75 %", "Background : In the past three decades , the incidence of colorectal cancer ( CRC ) in Norway has doubled , surpassing all other Nordic countries for both men and women to become the most frequently diagnosed cancer . A small-scale , r and omized study on flexible sigmoidoscopy ( FS ) screening in Telemark , Norway , has shown a reduction in accumulated CRC incidence after 13 years . The aim of our study was to evaluate the effect on CRC mortality and morbidity by screen detection of CRC and removal of precursor lesions ( polypectomy ) , and to test out the management and organization mimicking a countrywide screening service . A total of 13,823 men and women ( 1:1 ) , age 55 - 64 years , were drawn r and omly from the population registries in Oslo ( urban ) and the county of Telemark ( mixed urban and rural ) and invited to have a screening examination . The rest of the relevant age cohorts constituted the control groups . In the screening group , 535 individuals were excluded according to exclusion criteria , rendering 13,288 individuals eligible for screening examination . Methods : A once only screening model was used . In the screening group , individuals were r and omized to have a once only FS or a combination of FS and faecal occult blood test ( FOBT ) . Results : The overall attendance rate was 8,849 out of 13,288 ( 67 % ) ; 73 % in Telemark and 60 % in Oslo . Attendance for FS only was 68 % and 65 % for combined FS&FOBT . Conclusions : The present FS/FS&FOBT screening study obtained a high acceptance rate for both screening modalities . The attendance rate was stable throughout the trial , suggesting an acceptable model for management of future countrywide screening", "BACKGROUND The purpose of this clinical trial was to compare efficacy and safety of the Boswellia serrata extract H15 with mesalazine for the treatment of active Crohn 's disease . PATIENTS AND METHODS R and omised , double-blind , verum-controlled , parallel group comparison for which 102 Patients were r and omised . The per protocol population included 44 patients treated with H15 and 39 patients treated with mesalazine . As primary outcome measure the change of the Crohn Disease Activity Index ( CDAI ) between the status of enrolment and end of therapy was chosen . H 15 was tested on non-inferiority compared to st and ard treatment with mesalazine . RESULTS The CDAI between the status of enrolment and end of therapy after treatment with H15 was reduced by 90 and after therapy with mesalazine by 53 scores in the mean . In this non-inferiority-trial the test hypothesis was confirmed by the statistical analysis . The difference between both treatments could not be proven to be statistically significant in favor to H15 for the primary outcome measure . The secondary efficacy endpoints confirm the assessment of the comparison of H15 and mesalazine . The proven tolerability of H15 completes the results of the shown clinical efficacy . CONCLUSIONS The study confirms that therapy with H15 is not inferior to mesalazine . This can be interpreted as evidence for the efficacy of H15 according to the state of art in the treatment of active Crohn 's disease with Boswellia serrata extract , since the efficacy of mesalazine for this indication has been approved by the health authorities . Considering both safety and efficacy of Boswellia serrata extract H15 it appears to be superior over mesalazine in terms of a benefit-risk-evaluation", "The clinical efficacy of a herbomineral formulation containing roots of Withania somnifera , the stem of Boswellia serrata , rhizomes of Curcuma longa and a zinc complex ( Articulin-F ) , was evaluated in a r and omized , double-blind , placebo controlled , cross-over study in patients with osteoarthritis . After a one-month single blind run-in period , 42 patients with osteoarthritis were r and omly allocated to receive either a drug treatment or a matching placebo for a period of three months . After a 15-day wash-out period the patients were transferred to the other treatment for a further period of three months . Clinical efficacy was evaluated every fortnight on the basis of severity of pain , morning stiffness , Ritchie articular index , joint score , disability score and grip strength . Other parameters like erythrocyte sedimentation rate and radiological examination were carried out on a monthly basis . Treatment with the herbomineral formulation produced a significant drop in severity of pain ( P less than 0.001 ) and disability score ( P less than 0.05 ) . Radiological assessment , however , did not show any significant changes in both the groups . Side effects observed with this formulation did not necessitate withdrawal of treatment", "AIM The aim of this study was to evaluate the patterns of compliance and the frequency of adenomas and neoplasms in a Swedish population . METHODS In 1996 , 2000 men and women born in 1935 or 1936 were selected at r and om from the population registers of Uppsala and Malmö/Lund . All subjects were invited by mail to participate . In a r and omised study design , subjects were either called up by a nurse to schedule the appointment for sigmoidoscopy or instructed to call themselves . At sigmoidoscopy subjects with a cancer , an adenoma ( neoplastic polyp ) or more than three hyperplastic polyps were scheduled for a complete colonoscopy . RESULTS Thirty-nine percent ( 770/1988 ) of all the invited subjects had a sigmoidoscopy . The participation differed between the two centres , 47 % at the Uppsala centre and 30 % at the Malmö/Lund centre ( P statistically significant difference between the two different invitation groups . In all , 98 subjects ( 13 % ) were planned for colonoscopy . Thirty-one ( 35 % ) of the subjects having a colonoscopy were women and 57 ( 65 % ) were men . Fifty-five true adenomas were found in 46 subjects . All together , six subjects had proximal adenomas . Five adenocarcinomas were diagnosed , all within the reach of the sigmoidoscope . CONCLUSIONS The compliance was lower and the adenomas were fewer than expected . To increase compliance it is necessary with rigorously controlled invitation routines", "Background and aims The objective of this study was to investigate the effect of Boswellia serrata extract ( BSE ) on symptoms , quality of life , and histology in patients with collagenous colitis . Material s and methods Patients with chronic diarrhea and histologically proven collagenous colitis were r and omized to receive either oral BSE 400 mg three times daily for 6 weeks or placebo . Complete colonoscopy and histology were performed before and after treatment . Clinical symptoms and quality of life were assessed by st and ardized question naires and SF-36 . The primary endpoint was the percentage of patients with clinical remission after 6 weeks ( stool frequency ≤3 soft /solid stools per day on average during the last week ) . Patients of the placebo group with persistent diarrhea received open-label BSE therapy for a further 6 weeks . Results Thirty-one patients were r and omized ; 26 patients were available for per- protocol - analysis . After 6 weeks , the proportion of patients in clinical remission was higher in the BSE group than in the placebo group ( per protocol 63.6 % ; 95%CI , 30.8–89.1 vs 26.7 % , 95%CI , 7.7–55.1 ; p = 0.04 ; intention-to-treat 43.8 % vs 26.7 % , p = 0.25 ) . Compared to placebo , BSE treatment had no effect on histology and quality of life . Five patients discontinued BSE treatment prematurely . Discontinuation was due to adverse events ( n = 1 ) , unwillingness to continue ( n = 3 ) , or loss to follow-up for unknown reasons ( n = 1 ) . Seven patients received open-label BSE therapy , five of whom achieved complete remission . Conclusions Our study suggests that BSE might be clinical ly effective in patients with collagenous colitis . Larger trials are clearly necessary to establish the clinical efficacy of BSE " ]	41189b36-06ff-11f0-808a-c43d1ab1c353
This systematic review and meta- analysis synthesis ed the post-1990 literature examining the effect of human milk on morbidity , specifically necrotising enterocolitis ( NEC ) , late onset sepsis ( LOS ) , retinopathy of prematurity ( ROP ) , bronchopulmonary dysplasia ( BPD ) and neurodevelopment in infants born ≤28 weeks ’ gestation and /or publications with reported infant mean birth weight of ≤1500 g. Online data bases including Medline , PubMed , CINAHL , Scopus , and the Cochrane Central Register of Controlled Trials were search ed , and comparisons were grouped as follows : exclusive human milk ( EHM ) versus exclusive preterm formula ( EPTF ) , any human milk ( HM ) versus EPTF , higher versus lower dose HM , and unpasteurised versus pasteurised HM . Experimental and observational studies were pooled separately in meta-analyses . Risk of bias was assessed for each individual study and the GRADE system used to judge the certainty of the findings . Forty-nine studies ( with 56 reports ) were included , of which 44 could be included in meta-analyses . HM provided a clear protective effect against NEC , with an approximate 4 % reduction in incidence . HM also provided a possible reduction in LOS , severe ROP and severe NEC . Particularly for NEC , any volume of HM is better than EPTF , and the higher the dose the greater the protection . Evidence regarding pasteurisation is inconclusive , but it appears to have no effect on some outcomes . Improving the intake of mother ’s own milk ( MOM ) and /or donor HM results in small improvements in morbidity in this population	[ "BACKGROUND Preterm infants are immunologically immature at birth . Previous studies have demonstrated that human milk protects against infection in full-term infants , but there are few studies of its effect for preterm infants . OBJECTIVE To examine the effect of human milk feedings on infection incidence among very low birth weight ( VLBW ) infants during their initial hospitalization . STUDY DESIGN The sample consisted of 212 consecutive VLBW infants admitted to the Georgetown University Medical Center neonatal intensive care unit ( NICU ) during 1992 - 1993 and surviving to receive enteral feeding . Type of feeding ( human milk vs formula ) , presence of infection and sepsis/meningitis ( clinical signs and positive cultures for pathogenic organisms ) , and potential confounding variables were abstract ed from medical records . Multiple logistic regression was used to control for confounders . RESULTS The incidence of infection ( human milk [ 29.3 % ] vs formula [ 47.2 % ] ) and sepsis/meningitis ( human milk [ 19.5 % ] vs formula [ 32.6 % ] ) differed significantly by type of feeding . Major risk factors for infection were similar in both groups . Human milk feeding was independently correlated with a reduced odds of infection ( odds ratio [ OR ] = 0.43 ; 95 % confidence interval [ CI ] : 0.23 - 0.81 ) , controlling for gestational age , 5-minute Apgar score , mechanical ventilation days , and days without enteral feedings ; and was independently correlated with a reduced odds of sepsis/meningitis ( OR = 0.47 , 95 % CI:0.23 - 0 . 95 ) , controlling for gestational age , mechanical ventilation days , and days without enteral feedings . CONCLUSIONS The incidence of any infection and sepsis/meningitis are significantly reduced in human milk-fed VLBW infants compared with exclusively formula-fed VLBW infants", "BACKGROUND . We previously reported beneficial effects of breast milk ingestion by infants with extremely low birth weight in the NICU on developmental outcomes at 18 months ’ corrected age . The objective of this study was to determine whether these effects of breast milk in infants with extremely low birth weight persisted at 30 months ’ corrected age . METHODS . Nutrition data , including enteral and parenteral feeds , were prospect ively collected , and 30 months ’ corrected age follow-up assessment s were completed on 773 infants with extremely low birth weight who participated in the National Institute of Child Health and Human Development Neonatal Research Network Glutamine Trial . A total of 593 ingested some breast milk during the neonatal hospitalization , and 180 ingested none . Neonatal feeding characteristics and morbidities and 30-month interim history , neurodevelopmental outcomes , and growth parameters were analyzed . Children were divided into quintiles of breast milk volume to evaluate the effects of volume of human milk ingested during the NICU hospitalization . RESULTS . At 30 months , increased ingestion of breast milk was associated with higher Bayley Mental Developmental Index scores , higher Bayley behavior score percentiles for emotional regulation , and fewer rehospitalizations between discharge and 30 months . There were no differences in growth parameters or cerebral palsy . For every 10 mL/kg per day increase in breast milk , the Mental Developmental Index increased by 0.59 points , the Psychomotor Developmental Index by 0.56 points , and the total behavior percentile score by 0.99 points , and the risk of rehospitalization between discharge and 30 months decreased by 5 % . CONCLUSIONS . Beneficial effects of ingestion of breast milk in the NICU persist at 30 months ’ corrected age in this vulnerable extremely low birth weight population . Continued efforts must be made to offer breast milk to all extremely low birth weight infants both in the NICU and after discharge", "OBJECTIVE To compare the duration of parenteral nutrition , growth , and morbidity in extremely premature infants fed exclusive diets of either bovine milk-based preterm formula ( BOV ) or donor human milk and human milk-based human milk fortifier ( HUM ) , in a r and omized trial of formula vs human milk . STUDY DESIGN Multicenter r and omized controlled trial . The authors studied extremely preterm infants whose mothers did not provide their milk . Infants were fed either BOV or an exclusive human milk diet of pasteurized donor human milk and HUM . The major outcome was duration of parenteral nutrition . Secondary outcomes were growth , respiratory support , and necrotizing enterocolitis ( NEC ) . RESULTS Birth weight ( 983 vs 996 g ) and gestational age ( 27.5 vs 27.7 wk ) , in BOV and HUM , respectively , were similar . There was a significant difference in median parenteral nutrition days : 36 vs 27 , in BOV vs HUM , respectively ( P = .04 ) . The incidence of NEC in BOV was 21 % ( 5 cases ) vs 3 % in HUM ( 1 case ) , P = .08 ; surgical NEC was significantly higher in BOV ( 4 cases ) than HUM ( 0 cases ) , P = .04 . CONCLUSIONS In extremely preterm infants given exclusive diets of preterm formula vs human milk , there was a significantly greater duration of parenteral nutrition and higher rate of surgical NEC in infants receiving preterm formula . This trial supports the use of an exclusive human milk diet to nourish extremely preterm infants in the neonatal intensive care unit", "Despite potential benefits , human milk may fail to meet preterm infants ' nutrient requirements . We tested the hypothesis that fortified breast milk , fed alone or with preterm formula , would improve neurodevelopment and growth at 18-mo follow-up without adverse short-term clinical or biochemical consequences . Two hundred seventy-five preterm infants from two medical centers ( birth weight were r and omly assigned to receive for a mean of 39 d a multinutrient fortifier or control supplement containing phosphate and vitamins . Breast milk comprised 47.6 % and 46.4 % of enteral intake in fortified and control groups , respectively ; preterm formula supplements were used when insufficient breast milk was available . Overall , there were no significant growth advantages with fortification ; although , when breast milk exceeded 50 % of intake , fortification promoted faster weight gain ( an advantage of 1.6 g.kg-1.d-1 ; 95 % CI : 0.1 , 3.1 ; P plasma urea from week 2 ( P = 0.04 ) , 2 ) higher plasma calcium ( mean 2.34 + /- 0.01 compared with 2.27 + /- 0.02 mmol/L ; P = 0.003 ) , 3 ) a greater rise in alkaline phosphatase by week 6 ( P = 0.04 ) , 4 ) more clinical infections ( suspected plus proven ; 43 % compared with 31 % , P = 0.04 ) , 5 ) a nonsignificantly increased incidence of necrotizing enterocolitis ( 5.8 % compared with 2.2 % , P = 0.12 ) , and 6 ) higher white cell and platelet counts . Developmental scores at 18 mo were slightly but not significantly higher in the fortified group . This study confirmed that breast milk fortifiers can improve short-term growth ( when breast milk intakes are high ) ; but beneficial effects on long-term development remained unproven . Future research is required to evaluate potential adverse consequences and explore more optimal fortification strategies", "Poor weight gain observed in preterm infants who were fed expressed breast milk compared with those fed a cows ' milk formular prompted a detailed study of early postnatal growth in preterm infants fed these two milks . 68 infants were divided into two categories by gestational age at birth ( i ) 28 - 32 weeks ( n=28 ) , ( ii ) 33 - 36 weeks ( n=40 ) . They were r and omly allocated to a feed of expressed breast milk or a milk formula ( Ostermilk 1 ) . Rates of weight gain , linear growth , and head circumference growth were evaluated over two periods : birth-1 month , 1 - 2 months . The younger group who were fed breast milk showed slower overall growth rates over the first month than those fed formula . In the second month , and for the older infants over both of the 2-monthly periods , growth rates were similar in the two feeding regimens . It is concluded that expressed breast milk is inadequate for the growth of very immature preterm infants during early postnatal life", "Background : Feeding preterm infants human milk has a beneficial effect on the risk of late-onset sepsis ( LOS ) . Due to lack of microbiological st and ards , practice s such as pasteurization of mother ’s own milk differ widely among neonatal intensive care units worldwide . Objectives : To investigate whether pasteurization of mother ’s own milk for very-low-birth-weight ( VLBW ) infants influences the incidence and severity of infection-related outcomes . Methods : In this r and omized controlled trial , preterm infants ( gestational age received either raw or pasteurized mother ’s own milk during the first 8 weeks of life . The primary outcome was the incidence of proven LOS . A dose-response relation was verified , i.e. the dependence of the risk of sepsis on the actual and cumulative quantities of mother ’s own milk . Results : This study included 303 VLBW infants ( mean birth weight : 1,276 g ; mean gestational age : 29 weeks ) whose baseline and nutritional characteristics were similar . The incidence of laboratory-confirmed sepsis was not statistically different in infants fed raw milk compared to infants who received pasteurized milk : 22/151 ( 0.15 , CI : 0.08–0.20 ) and 31/152 ( 0.20 , CI : 0.14–0.27 ) , respectively ( RR : 0.71 ; 95 % CI : 0.43–1.17 ) . A significant dose-response relation was observed between the adjusted quantity of enteral feeding and the risk of LOS , regardless of the type of feeding . Conclusion : For preterm infants , pasteurization of mother ’s own milk shows a trend towards an increase in infectious morbidity , although no statistical significance was reached . Practice s should focus on collection , storage and labeling procedures to ensure the safety and quality of expressed milk", "OBJECTIVE This study tested the hypothesis that feeding an exclusively human milk ( EHM ) diet to premature infants reduces the incidence of necrotizing enterocolitis ( NEC ) associated with enteral feeding . STUDY DESIGN An observational study for infants born at less than 33 weeks of gestational age was performed in a single neonatal intensive care unit . An EHM diet prospect ively eliminated bovine-based artificial milk , including bovine-based fortifier , through 33 weeks postmenstrual age ( PMA ) . The clinical data from a 2.5-year interval of the EHM diet were compared with data from the previous 6.5 years for similar infants who received bovine-based milk products before 33 weeks PMA . RESULTS In the EHM diet cohort , 148 of 162 infants ( 91 % ) received EHM through 33 weeks PMA . In order to achieve an EHM diet , 140 of 162 infants ( 86 % ) received their own mother 's milk , and 98 of 162 infants ( 60 % ) received donor human milk . The EHM cohort was also fed a human milk-based fortifier to truly eliminate bovine products . The distribution of NEC onset in the EHM cohort was significantly different from that in the control cohort for the day of onset ( p=0.042 ) and the PMA at onset ( p=0.011 ) . In the control cohort , NEC onset after Day 7 of life occurred in 15 of 443 infants ( 3.4 % ) , significantly more than in the EHM cohort where NEC occurred in two of 199 infants ( 1 % ) ( p=0.009 ) . CONCLUSIONS Changing to an EHM milk diet through 33 weeks PMA reduced the incidence of NEC associated with enteral feeding", "BACKGROUND Retinopathy of prematurity(ROP ) is the most common serious ophthalmic disease in preterm infants . Human milk may provide a protective effect for ROP ; however , beneficial effects of human milk preclude r and omized trials . Therefore , we conducted a retrospective analysis comparing early postnatal nutrition with ROP development . OBJECTIVE Evaluate relationship between early postnatal nutriture and ROP surgery . DESIGN / METHODS Nutrition data was collected for inborn AGA infants , BW 700 - 1000 g. ROP surgery was the primary outcome variable . A single pediatric ophthalmologist supervised examinations . All infants received triweekly IM vitamin A as chronic lung disease prophylaxis ( Tyson : NEJM , 1999 ) . RESULTS BW and gestational age were 867+/-85 g and 26.3+/-1.2 weeks ( n=77 , mean+/-1SD ) . ROP surgery infants(n=11 ) received more parenteral nutrition , 1648 mL , and less human milk , 13.8 mL/kg-day , and vitamin E , 1.4 mg/kg-day , during the second postnatal week . Human milk was a negative predictor for ROP surgery , odds ratio=0.94 . Both groups met vitamin A recommendations ; however , 74 % was administered via IM injections . Neither group met vitamin E recommendations . CONCLUSIONS Human milk feeding , parenteral nutrition volume and vitamin E intake were predictors for ROP surgery . IM vitamin A injections provided the majority of vitamin A ; vitamin E administration was insufficient . Improving human milk feeding rates and vitamin dosing options may affect ROP surgery rates", "Background In a recent meta- analysis , human milk feeding of low birth-weight ( LBW ) infants was associated with a 5.2 point improvement in IQ tests . However , in the studies in this meta- analysis , feeding regimens were used ( unfortified human milk , term formula ) that no longer represent recommended practice . Objective To compare the growth , in-hospital feeding tolerance , morbidity , and development ( cognitive , motor , visual , and language ) of LBW infants fed different amounts of human milk until term chronologic age ( CA ) with those of LBW infants fed nutrient-enriched formulas from first enteral feeding . Methods The data in this study were collected in a previous r and omized controlled trial assessing the benefit of supplementing nutrient-enriched formulas for LBW infants with arachidonic acid and docosahexaenoic acid . Infants ( n = 463 , birth weight , 750–1,800 g ) were enrolled from nurseries located in Chile , the United Kingdom , and the United States . If human milk was fed before hospital discharge , it was fortified ( 3,050–3,300 kJ/L , 22–24 kcal/oz ) . As infants were weaned from human milk , they were fed nutrient-enriched formula with or without arachidonic and docosahexaenoic acids ( 3,300 kJ/L before term , 3,050 kJ/L thereafter ) until 12 months CA . Formula fed infants were given nutrient-enriched formula with or without added arachidonic and docosahexaenoic acids ( 3,300 kJ/L to term , 3,050 kJ/L thereafter ) until 12 months CA . For the purpose s of this evaluation , infants were categorized into four mutually exclusive feeding groups : 1 ) predominantly human milk fed until term CA ( PHM-T , n = 43 ) ; 2 ) ≥ 50 % energy from human milk before hospital discharge ( ≥ 50 % HM , n = 98 ) ; 3 ) from human milk before hospital discharge ( weighed approximately 500 g more at term CA than did PHM-T infants . This absolute difference persisted until 6 months CA . PFF-T infants were also longer ( 1.0–1.5 cm ) and had larger head circumferences ( 0.3–1.1 cm ) than both PHM-T and ≥ 50 % HM infants at term CA . There was a positive association between duration of human milk feeding and the Bayley Mental Index at 12 months CA ( P = 0.032 full and P = 0.073 reduced , statistical models ) after controlling for the confounding variables of home environment and maternal intelligence . Infants with chronic lung disease fed ≥ 50 % HM until term CA ( n = 22 ) had a mean Bayley Motor Index about 11 points higher at 12 months CA compared with infants PFF-T ( n = 24 , P = 0.033 full model ) . Conclusion Our data suggest that , despite a slower early growth rate , human milk fed LBW infants have development at least comparable to that of infants fed nutrient-enriched formula . Exploratory analysis suggests that some subgroups of human milk fed LBW infants may have enhanced development , although this needs to be confirmed in future studies", "A large multicentre study on the short and long term clinical and developmental outcome of infants r and omised to different diets is being undertaken . This report represents an interim analysis of the early postnatal growth performance of an unselected population of 194 preterm infants ( gestation , mean ( SD ) 31 . 0 ( 2 . 9 ) weeks ; birthweight , mean ( SD ) 1364 ( 294 ) g ) , both ill and well , examined in two ( of four ) parallel trials . One trial compared banked breast milk with a new preterm formula ( primary trial ) ; the other compared these diets as supplements to maternal milk ( supplement trial ) . A major dietary effect on the number of days taken to regain birthweight and subsequent gains in weight , length , and head circumference was observed in the primary trial . Infants fed banked breast milk and weighing less than 1200 g at birth took a calculated additional three weeks to reach 2000 g compared with those fed on the preterm formula . A significant influence of diet on body proportions was seen in the relation between body weight , head circumference , and length . Similar though smaller differences in growth patterns were seen in the supplement trial . By the time they reach 2000 g , infants of birthweights 1200 to 1849 g fed on banked breast milk and infants below 1200 g fed on either banked breast milk or maternal milk supplemented ( as necessary ) with banked breast milk , fulfilled stringent criteria for failure to thrive ( weight less than 2 SD below the mean for age ) . Only infants fed the preterm formula as their sole diet had maintained their birth centile by discharge from hospital . The misleading nature of comparisons between extrauterine and intrauterine steady state weight gains is emphasised", "PURPOSE To determine the influence of breastmilk consumption , as a dose response , in very low-birth-weight ( VLBW ) infants ( on neurodevelopmental outcomes at 6 and 12 months corrected age , and to determine the influence of selected sociodemographic and infant variables on neurodevelopmental outcomes . SUBJECTSVLBW infants ( n = 148 ) who were fed mother 's milk or formula by parental choice . DESIGN Prospect i ve cohort with longitudinal follow-up at 6 and 12 months corrected age . METHODS Self-administered question naires given to mothers at study entry , before discharge , and at 3- , 6- , and 12-month follow-up visits . During hospitalization , mothers recorded the 24-hour volume of expressed milk once per week . At each follow-up visit , the volume of a single feeding was assessed by pre- and postbreastfeeding test weights of infants measured on an electronic scale accurate to 1.0 g. The amount of breastfeeding was also assessed by feeding records and mother 's report . MAIN OUTCOME MEASURES The Bayley Scales of Infant Development ( 2nd Edition ) , the Mental Development Index ( MDI ) , and the Psychomotor Development Index ( PDI ) . PRINCIPAL RESULTS After controlling for specific sociodemographic and infant variables , this study of VLBW infants showed no statistically significant effect of predominantly breastfeeding compared with predominantly formula feeding on neurodevelopmental outcomes to 12 months corrected age . The most significant predictor of MDI scores at 6 and 12 months corrected age was birth weight , in which higher birth weights predicted higher MDI scores . CONCLUSIONS Despite the lack of statistically significant differences , the findings suggest a small but consistent advantage in developmental scores in infants who were fed their mother 's milk compared with those who were predominantly formula fed . Supporting parents to breastfeed preterm infants may maximize the potential advantages of early nutrition in the neurodevelopmental outcome of VLBW infants", "Background : Necrotizing enterocolitis ( NEC ) is a frequent cause of mortality and morbidity in very low birth weight ( VLBW ) infants . Human milk ( HM ) feeding has been associated with lower risk of NEC . However , mothers of VLBW infants often experience insufficient milk production , result ing in mixed feedings of HM and formula . Moreover , medical complications often limit the volume of feeding they can be given . Objective : To determine if high proportions of ( 50 % or greater ) HM enteral feeding within the first 14 days of life are protective against NEC . Method : This was a prospect i ve cohort study of VLBW infants who were grouped according to the HM proportion of enteral feeding in the first 14 days : LHM , n=46 ) and ⩾50 % ( high human milk , HHM , n=156 ) . The outcome of interest was development of NEC ( Bell stage 2 or 3 ) . Logistic regression was used to estimate odds ratios ( OR ) and 95 % confidence intervals ( CI ) and to assess potential confounding due to perinatal risk factors . Result : Two hundred and two infants were studied . Confirmed NEC occurred in 5/46 ( 10.6 % ) of the LHM group , as compared with 5/156 ( 3.2 % ) of the HHM . Gestational age was the only perinatal factor associated with risk of NEC . After adjustment for gestational age , HHM was associated with a lower risk of NEC ( ( OR=0.17 , 95 % CI : 0.04 to 0.68 ) , P=0.01 ) . Conclusion : Enteral feeding containing at least 50 % HM in the first 14 days of life was associated with a sixfold decrease in the odds of NEC ", "Objective : To study the incidence of sepsis and neonatal intensive care unit ( NICU ) costs as a function of the human milk ( HM ) dose received during the first 28 days post birth for very low birth weight ( VLBW ) infants . Study design : Prospect i ve cohort study of 175 VLBW infants . The average daily dose of HM ( ADDHM ) was calculated from daily nutritional data for the first 28 days post birth ( ADDHM-Days 1–28 ) . Other covariates associated with sepsis were used to create a propensity score , combining multiple risk factors into a single metric . Result : The mean gestational age and birth weight were 28.1±2.4 weeks and 1087±252 g , respectively . The mean ADDHM-Days 1–28 was 54±39 ml kg−1 day−1 ( range 0–135 ) . Binary logistic regression analysis controlling for propensity score revealed that increasing ADDHM-Days 1–28 was associated with lower odds of sepsis ( odds ratio 0.981 , 95 % confidence interval 0.967–0.995 , P=0.008 ) . Increasing ADDHM-Days 1–28 was associated with significantly lower NICU costs . Conclusion : A dose – response relationship was demonstrated between ADDHM-Days 1–28 and a reduction in the odds of sepsis and associated NICU costs after controlling for propensity score . For every HM dose increase of 10 ml kg−1 day−1 , the odds of sepsis decreased by 19 % . NICU costs were lowest in the VLBW infants who received the highest ADDHM-Days 1–28", "OBJECTIVE To evaluate the health benefits of an exclusively human milk-based diet compared with a diet of both human milk and bovine milk-based products in extremely premature infants . STUDY DESIGN Infants fed their own mothers ' milk were r and omized to 1 of 3 study groups . Groups HM100 and HM40 received pasteurized donor human milk-based human milk fortifier when the enteral intake was 100 and 40 mL/kg/d , respectively , and both groups received pasteurized donor human milk if no mother 's milk was available . Group BOV received bovine milk-based human milk fortifier when the enteral intake was 100 mL/kg/d and preterm formula if no mother 's milk was available . Outcomes included duration of parenteral nutrition , morbidity , and growth . RESULTS The 3 groups ( total n = 207 infants ) had similar baseline demographic variables , duration of parenteral nutrition , rates of late-onset sepsis , and growth . The groups receiving an exclusively human milk diet had significantly lower rates of necrotizing enterocolitis ( NEC ; P = .02 ) and NEC requiring surgical intervention ( P = .007 ) . CONCLUSIONS For extremely premature infants , an exclusively human milk-based diet is associated with significantly lower rates of NEC and surgical NEC when compared with a mother 's milk-based diet that also includes bovine milk-based products", "Few data from r and omised prospect i ve studies address whether early diet influences later neurodevelopment in man . As part of a larger multicentre trial , 502 low birthweight infants were assigned r and omly , for a median of 30 days , to receive a preterm formula or unfortified donor breast milk as sole diets or as supplements to their mothers ' expressed milk . Surviving infants were assessed at nine months after their expected date of delivery without knowledge of their feeding regimen . The mean developmental quotient was 0.25 st and ard deviations lower in those fed donor breast milk rather than preterm formula . In infants fed their mother 's expressed milk , however , the disadvantage of receiving banked milk compared with preterm formula as a supplement , was greater when the supplement was over half the total intake , and approached five points , representing 0.5 st and ard deviations for developmental quotient . Infants fed donor breast milk were at particular disadvantage following fetal growth retardation , with developmental quotients 5.3 points lower . We suggest that the diet used for low birthweight babies over a brief , but perhaps critical , postnatal period has developmental consequences that persist into infancy ; infants who are small for gestational age are especially vulnerable to suboptimal postnatal nutrition", "Background Human milk from the infant 's mother ( own mother 's milk ; OMM ) feedings reduces the risk of several morbidities in very low birthweight ( VLBW ) infants , but limited data exist regarding its impact on bronchopulmonary dysplasia ( BPD ) . Objective To prospect ively study the impact of OMM received in the neonatal intensive care unit ( NICU ) on the risk of BPD and associated costs . Design / methods A 5-year prospect i ve cohort study of the impact of OMM dose on growth , morbidity and NICU costs in VLBW infants . OMM dose was the proportion of enteral intake that consisted of OMM from birth to 36 weeks postmenstrual age ( PMA ) or discharge , whichever occurred first . BPD was defined as the receipt of oxygen and /or positive pressure ventilation at 36 weeks PMA . NICU costs included hospital and physician costs . Results The cohort consisted of 254 VLBW infants with mean birth weight 1027±257 g and gestational age 27.8±2.5 weeks . Multivariable logistic regression demonstrated a 9.5 % reduction in the odds of BPD for every 10 % increase in OMM dose ( OR 0.905 ( 0.824 to 0.995 ) ) . After controlling for demographic and clinical factors , BPD was associated with an increase of US$ 41 929 in NICU costs . Conclusions Increased dose of OMM feedings from birth to 36 weeks PMA was associated with a reduction in the odds of BPD in VLBW infants . Thus , high-dose OMM feeding may be an inexpensive , effective strategy to help reduce the risk of this costly multifactorial morbidity", "OBJECTIVE To examine the dose effect of maternal milk on neonatal morbidity of very low-birth-weight ( DESIGN Prospect i ve observational study . SETTING An urban tertiary care neonatal intensive care unit and follow-up clinic . POPULATION One hundred nineteen singleton very low-birth-weight infants admitted from January 1 , 1997 , to February 14 , 1999 ( mean birth weight , 1056 g ; mean gestational age , 28 weeks ; 57 % male ; and 43 % white ) . METHODS A comparison of the effect on neonatal outcomes of daily grade d doses ( 1 - 24 , 25 - 49 , and > or = 50 mL/kg of body weight ) of maternal milk through week 4 of life vs a reference group receiving no maternal milk . MAIN OUTCOME MEASURES Neonatal outcomes examined included rates of sepsis after age 5 days , retinopathy of prematurity , chronic lung disease , necrotizing enterocolitis , jaundice , duration of ventilator dependence , and length of hospital stay . RESULTS Seventy-nine infants ( 66 % ) received maternal milk , of whom 32 received at least 50 mL/kg per day through week 4 of life . Poisson regression analysis adjusting for birth weight , sex , and ethnicity revealed that the mean number of episodes of sepsis for infants receiving at least 50 mL/kg per day was lower by a factor of 0.27 ( 95 % confidence interval , 0.08 - 0.95 ) compared with infants receiving no maternal milk . There was no effect of maternal milk on other neonatal outcomes . CONCLUSIONS A daily threshold amount of at least 50 mL/kg of maternal milk through week 4 of life is needed to decrease the rate of sepsis in very low-birth-weight infants , but maternal milk does not affect other neonatal morbidities", "My colleagues and I compared the biochemical status and rates of growth of three groups of preterm infants : one group was fed milk obtained early from mothers of preterm infants ; one group received milk produced during the mature stage of lactation by mothers of term infants ; and one group received a whey-based infant formula . Sixty healthy preterm infants with birth weights of 1600 g or less were r and omly assigned to one of the three feedings groups . The 20 infants in each group were followed until they reached a weight of 1800 g. The mean ( + /- S.E.M. ) number of days required to regain birth weight was similar for infants receiving the formula ( 10.3 + /- 0.8 ) and those receiving milk from mothers of preterm infants ( 11.4 + /- 0.8 ) ; both were significantly less than the number ( 18.8 + /- 1.7 ) for infants receiving milk from mothers of term infants ( P less than 0.001 ) . Subsequent rates of weight gain were greater for the groups receiving formula ( 27.0 + /- 0.8 g per day ) and milk from mothers of preterm infants ( 23.7 + /- 1.1 ) than for the group receiving milk from mothers of term infants ( 15.8 + /- 0.8 ) ( P less than 0.001 ) . Similarly , the average increments in crown-to-heel length and in the head circumference were significantly greater for the groups given formula and milk from mothers of preterm infants ( P less than 0.005 and P less than 0.001 , respectively ) . These data indicate that feeding with either milk from mothers of preterm infants or a whey-based infant formula results in more appropriate growth in preterm infants than feeding with milk from mothers of term infants", "In a prospect i ve controlled study the anti-infective properties of breast-milk were evaluated in 70 high-risk low-birth-weight infants . 32 babies ( group I ) were given fresh expressed breast-milk during the day and milk formula at night . 38 infants ( group II ) received only milk formula and served as controls . The two groups were matched for other factors that could influence the occurrence of infection . The incidence of infections was significantly less ( p < 0.01 ) in babies who received breast-milk", "Objective . Compared with preterm formula ( PF ) , mother 's milk ( MM ) is associated with lower rates of late-onset sepsis ( LOS ) and necrotizing enterocolitis ( NEC ) among premature infants . Because not all mothers of premature infants produce sufficient milk to supply their infants throughout hospitalization , we reasoned that pasteurized donor human milk ( DM ) would be a suitable alternative . Methods . Extremely premature infants ( were assigned r and omly to receive either pasteurized DM or PF if the supply of their own MM became insufficient during the study ( birth to 90 days of age or hospital discharge ) . Infection-related events ( LOS , NEC , meningitis , presumed sepsis , or urinary tract infection ) that occurred after the attainment of a milk intake of 50 mL/kg , dietary intake , growth , skin-to-skin contact , and duration of hospital stay were compared . The primary analysis compared groups DM and PF on an intent-to-treat basis . If no differences were noted , then these groups were combined and compared with the reference group , group MM . If differences were noted , then the subsequent analyses compared each group with group MM . Results . Of 243 infants , 70 ( 29 % ) received only MM ; group DM included 81 infants and group PF included 92 infants . Because of poor weight gain , 17 infants ( 21 % ) , all in group DM , were switched to PF . There were no differences in birth weight , gestational age , multiple births , and age at attainment of feeding of 50 mL/kg among groups . There were no differences between group DM and group PF in LOS and /or NEC , other infection-related events , hospital stay , or number of deaths . Group DM received a greater intake of milk and more nutritional supplements but had a slower rate of weight gain , compared with group PF . Compared with groups DM and PF , group MM had fewer episodes of LOS and /or NEC and total infection-related events and a shorter duration of hospital stay . Group MM also had fewer Gram-negative organisms isolated from blood cultures than did the other groups . Conclusions . In this r and omized , blinded trial of feeding of extremely premature infants , we found that , as a substitute for MM , DM offered little observed short-term advantage over PF for feeding extremely premature infants . Advantages to an exclusive diet of MM were observed in terms of fewer infection-related events and shorter hospital stays", "In a prospect i ve multicentre study on 926 preterm infants formally assigned to their early diet , necrotising enterocolitis developed in 51 ( 5.5 % ) . Mortality was 26 % in stringently confirmed cases . In exclusively formula-fed babies confirmed disease was 6 - 10 times more common than in those fed breast milk alone and 3 times more common than in those who received formula plus breast milk . Pasteurised donor milk seemed to be as protective as raw maternal milk . Among babies born at more than 30 weeks ' gestation confirmed necrotising enterocolitis was rare in those whose diet included breast milk ; it was 20 times more common in those fed formula only . Other risk factors included very low gestational age , respiratory disease , umbilical artery catheterisation , and polycythaemia . In formula-fed but not breast-milk-fed infants , delayed enteral feeding was associated with a lower frequency of necrotising enterocolitis . With the fall in the use of breast milk in British neonatal units , exclusive formula feeding could account for an estimated 500 extra cases of necrotising enterocolitis each year . About 100 of these infants would die", "Background : Most preterm infants who develop necrotising enterocolitis ( NEC ) have received enteral feeds . Uncertainty exists about which aspects of the feeding regimen affect the risk of NEC . Aim : To examine associations between various enteral feeding practice s and the development of NEC in preterm infants . Methods : Multicentre case – control study . 53 preterm infants with NEC were enrolled together with a gestational age frequency-matched control without NEC from a r and omly selected neonatal unit . Clinical and feeding data were extracted and compared between the groups . Results : Significantly fewer cases than controls had received human breast milk ( 75 % vs 91 % ; OR 0.32 , 95 % CI 0.11 to 0.98 ) . The day on which enteral feeding was started did not differ significantly ( mean ( SD ) days after birth : cases 2.9 ( 2.8 ) and controls 2.8 ( 1.8 ) ) . The mean ( SD ) duration of trophic feeding ( fully fed significantly earlier than controls ( mean ( SD ) days after birth : cases 9.9 ( 4.2 ) and controls 14.3 ( 9.8 ) ; MD −4.4 , 95 % CI −7.3 to −1.5 ) . Conclusions : These data suggest that the duration of trophic feeding and rate of advancement of feed volumes may be modifiable risk factors for NEC in preterm infants . Further r and omised controlled trials are warranted to assess the effect of different rates of feed advancement on the incidence of NEC , as well as other outcomes", "Background Following publication of the PRISMA statement , the UK Centre for Review s and Dissemination ( CRD ) at the University of York in Engl and began to develop an international prospect i ve register of systematic review s with health-related outcomes . The objectives were to reduce unplanned duplication of review s and provide transparency in the review process , with the aim of minimizing reporting bias . Methods An international advisory group was formed and a consultation undertaken to establish the key items necessary for inclusion in the register and to gather views on various aspects of functionality . This article describes the development of the register , now called PROSPERO , and the process of registration . Results PROSPERO offers free registration and free public access to a unique prospect i ve register of systematic review s across all areas of health from all around the world . The dedicated web-based interface is electronically search able and available to all prospect i ve registrants . At the moment , inclusion in PROSPERO is restricted to systematic review s of the effects of interventions and strategies to prevent , diagnose , treat , and monitor health conditions , for which there is a health-related outcome .Ideally , registration should take place before the research ers have started formal screening against inclusion criteria but review s are eligible as long as they have not progressed beyond the point of completing data extraction .The required data set captures the key attributes of review design as well as the administrative details necessary for registration .Su bmi tted registration forms are checked against the scope for inclusion in PROSPERO and for clarity of content before being made publicly available on the register , rejected , or returned to the applicant for clarification . The public records include an audit trail of major changes to planned methods , details of when the review has been completed , and links to result ing publications when provided by the authors . Conclusions There has been international support and an enthusiastic response to the principle of prospect i ve registration of protocol s for systematic review s and to the development of PROSPERO .In October 2011 , PROSPERO contained 200 records of systematic review s being undertaken in 26 countries around the world on a diverse range of interventions", "IMPORTANCE Infections and necrotizing enterocolitis , major causes of mortality and morbidity in preterm infants , are reduced in infants fed their own mother 's milk when compared with formula . When own mother 's milk is not available , human donor milk is considered a good alternative , albeit an expensive one . However , most infants at modern neonatal intensive care units are predominantly fed with own mother 's milk . The benefits of add-on donor milk over formula are not clear . OBJECTIVE To determine whether providing donor milk instead of formula as supplemental feeding whenever own mother 's milk is insufficiently available during the first 10 days of life reduces the incidence of serious infection , necrotizing enterocolitis , and mortality . DESIGN , SETTING S , AND PARTICIPANTS The Early Nutrition Study was a multicenter , double-blind r and omized clinical trial in very low-birth-weight infants ( birth weight Intent-to-treat analysis was performed . INTERVENTIONS Infants received pasteurized donor milk or preterm formula during the first 10 days of life if own mother 's milk was not ( sufficiently ) available . MAIN OUTCOMES AND MEASURES The primary end point was cumulative occurrence of serious infection ( sepsis or meningitis ) , necrotizing enterocolitis , or mortality during the first 60 days of life . RESULTS A total of 930 infants were screened for inclusion ; 557 were excluded , result ing in 373 infants ( 183 receiving donor milk and 190 receiving formula ) who were evaluated by intent-to-treat analysis ( median birth weight , 1066 g ; mean gestational age , 28.4 weeks ) . Own mother 's milk comprised 89.1 % and 84.5 % of total mean intake during the intervention period for the donor milk and formula groups , respectively . The incidence of the combined outcome was not different ( 85 [ 44.7 % ] [ formula ] vs 77 [ 42.1 % ] [ donor milk ] ; mean difference , 2.6 % ; 95 % CI , -12.7 % to 7.4 % ) . The adjusted hazard ratio was 0.87 ( 95 % CI , 0.63 - 1.19 ; P = .37 ) . CONCLUSIONS AND RELEVANCE In the current study , pasteurized donor milk and preterm formula as supplemental feeding during the first 10 days of life yielded similar short-term outcomes in very low-birth-weight infants regarding safety and efficacy when own mother 's milk availability was insufficient . Future studies investigating longer duration of use of human donor milk on short-term and long-term outcomes are necessary . TRIAL REGISTRATION trialregister.nl Identifier : NTR3225", "Background : Necrotizing enterocolitis ( NEC ) is a costly morbidity in very low birth weight ( VLBW ; that increases hospital length of stay and requires expensive treatments . Objectives : To evaluate the cost of NEC as a function of dose and exposure period of human milk ( HM ) feedings received by VLBW infants during the neonatal intensive care unit ( NICU ) hospitalization and determine the drivers of differences in NICU hospitalization costs for infants with and without NEC . Methods : This study included 291 VLBW infants enrolled in an NIH-funded prospect i ve observational cohort study between February 2008 and July 2012 . We examined the incidence of NEC , NICU hospitalization cost , and cost of individual re sources used during the NICU hospitalization . Results : Twenty-nine ( 10.0 % ) infants developed NEC . The average total NICU hospitalization cost ( in 2012 USD ) was USD 180,163 for infants with NEC and USD 134,494 for infants without NEC ( p = 0.024 ) . NEC was associated with a marginal increase in costs of USD 43,818 , after controlling for demographic characteristics , risk of NEC , and average daily dose of HM during days 1 - 14 ( p of HM during days 1 - 14 decreased non-NEC-related NICU costs by USD 534 ( p exclusive HM feedings during the first 14 days of life is an effective strategy to reduce the risk of NEC and result ing NICU costs in VLBW infants . Hospitals investing in initiatives to feed exclusive HM during the first 14 days of life could substantially reduce NEC-related NICU hospitalization costs", "Supplementary formula feeds inhibited the protective effect of expressed raw and pasteurised human milk in 226 high-risk neonates in a r and omised controlled trial . The infection rate in the group given pasteurised human milk and formula ( 33 % ) was significantly higher than the rates in the groups given raw human milk ( 10.5 % ) , pasteurised human milk ( 14.3 % ) , and raw human milk and formula ( 16 % ) . This accords with the impressions that some of the association of infection with artificial feeding is partly attributable to the lack of the protective effect of human milk . Heating expressed human milk to 62.5 degrees C for 30 min significantly reduces its protective effect", "OBJECTIVE . Beneficial effects of breast milk on cognitive skills and behavior ratings have been demonstrated previously in term and very low birth weight infants . Extremely low birth weight infants are known to be at increased risk for developmental and behavior morbidities . The benefits of breast milk that is ingested in the NICU by extremely low birth weight infants on development and behavior have not been evaluated previously . METHODS . Nutrition data including enteral and parenteral feeds were collected prospect ively , and follow-up assessment s of 1035 extremely low birth weight infants at 18 months ’ corrected age were completed at 15 sites that were participants in the National Institute of Child Health and Human Development Neonatal Research Network Glutamine Trial between October 14 , 1999 , and June 25 , 2001 . Total volume of breast milk feeds ( mL/kg per day ) during hospitalization was calculated . Neonatal characteristics and morbidities , interim history , and neurodevelopmental and growth outcomes at 18 to 22 months ’ corrected age were assessed . RESULTS . There were 775 ( 74.9 % ) infants in the breast milk and 260 ( 25.1 % ) infants in the no breast milk group . Infants in the breast milk group were similar to those in the no breast milk group in every neonatal characteristic and morbidity , including number of days of hospitalization . Mean age of first day of breast milk for the breast milk infants was 9.3 ± 9 days . Infants in the breast milk group began to ingest non – breast milk formula later ( 22.8 vs 7.3 days ) compared with the non – breast milk group . Age at achieving full enteral feeds was similar between the breast milk and non – breast milk groups ( 29.0 ± 18 vs 27.4 ± 15 ) . Energy intakes of 107.5 kg/day and 105.9 kg/day during the hospitalization did not differ between the breast milk and non – breast milk groups , respectively . At discharge , 30.6 % of infants in the breast milk group still were receiving breast milk . Mothers in the breast milk group were significantly more likely to be white ( 42 % vs 27 % ) , be married ( 50 % vs 30 % ) , have a college degree ( 22 % vs 6 % ) , and have private health insurance ( 34 % vs 18 % ) compared with the no breast milk group . Mothers who were black , had a low household income ( ≤$20000 ) , or had higher parity were less likely to provide breast milk feeds . The analysis of outcomes between the any human milk and no human milk groups were adjusted for maternal age , maternal education , marital status , race/ethnicity , and the other st and ard covariates . Children in the breast milk group were more likely to have a Bayley Mental Development Index ≥85 , higher mean Bayley Psychomotor Development Index , and higher Bayley Behavior Rating Scale percentile scores for orientation/engagement , motor regulation , and total score . There were no differences in the rates of moderate to severe cerebral palsy or blindness or hearing impairment between the 2 study groups . There were no differences in the mean weight ( 10.4 kg vs 10.4 kg ) , length ( 80.5 cm vs 80.5 cm ) , or head circumference ( 46.8 cm vs 46.6 cm ) for the breast milk and no breast milk groups , respectively , at 18 months . Multivariate analyses , adjusting for confounders , confirmed a significant independent association of breast milk on all 4 primary outcomes : the mean Bayley ( Mental Development Index , Psychomotor Development Index , Behavior Rating Scale , and incidence of rehospitalization ) . For every 10-mL/kg per day increase in breast milk ingestion , the Mental Development Index increased by 0.53 points , the Psychomotor Development Index increased by 0.63 points , the Behavior Rating Scale percentile score increased by 0.82 points , and the likelihood of rehospitalization decreased by 6 % . In an effort to identify a threshold effect of breast milk on Bayley Mental Development Index and Psychomotor Development Index scores and Behavior Rating Scale percentile scores , the mean volume of breast milk per kilogram per day during the hospitalization was calculated , and infants in the breast milk group were divided into quintiles of breast milk ingestion adjusted for confounders . Overall , the differences across the feeding quintiles of Mental Development Index and Psychomotor Development Index were significant . There was a 14.0 % difference in Behavior Rating Scale scores between the lowest and highest quintiles . For the outcomes ( Mental Development Index , Psychomotor Development Index , Behavior Rating Scale , and Rehospitalization , only the values for the > 80th percentile quintile of breast milk feeding were significantly different from the no breast milk values . In our adjusted regression analyses , every 10 mL/kg per day breast milk contributed 0.53 points to the Bayley Mental Development Index ; therefore , the impact of breast milk ingestion during the hospitalization for infants in the highest quintile ( 110 mL/kg per day ) on the Bayley Mental Development Index would be 10 × 0.53 , or 5.3 points . CONCLUSIONS . An increase of 5 points potentially would optimize outcomes and decrease costs by decreasing the number of very low birth weight children who require special education services . The societal implication s of a 5-point potential difference ( one third of an SD ) in IQ are substantial . The potential long-term benefit of receiving breast milk in the NICU for extremely low birth weight infants may be to optimize cognitive potential and reduce the need for early intervention and special education services" ]	41189b72-06ff-11f0-808a-c43d1ab1c353
The objective of the present systematic review and meta- analysis was to synthesize the available literature data investigating the effects of low glycaemic index/low glycamic load dietary regimens on anthropometric parameters , blood lipid profiles , and indicators of glucose metabolism in children and adolescents . Literature search was performed using the electronic data bases MEDLINE , EMBASE , and the Cochrane Central Register of trials with restrictions to r and omized controlled trials , but no limitations concerning language and publication date . Parameters taken into account were : body weight , body mass index , z-score of body mass index , fat mass , fat-free mass , height , waist cicrumference , hip circumference , waist-to-hip ratio , total cholesterol , LDL-cholesterol , HDL-cholesterol , triglycerides , diastolic and systolic blood pressure , fasting serum glucose , fasting serum insulin , HOMA-index , glycosylated haemoglobin , and C-reactive protein . Meta-analyses were performed for each parameter to assess pooled effect in terms of weighted mean differences between the post-intervention ( or differences in means ) of the low glycaemic index diets and the respective high glycaemic index counterparts . Data analysis was performed using the Review Manager 5.3 . software . Nine studies enrolling 1.065 children or adolescents met the inclusion criteria . Compared to diets providing a high gylcaemic index , low glycaemic index protocol s result ed in significantly more pronounced decreases in serum triglycerides [ mean differences −15.14 mg/dl , 95 % -CI ( −26.26 , −4.00 ) ] and HOMA-index [ mean difference −0.70 , 95 % -CI ( −1.37 , −0.04 ) , fixed-effects model only ] . Other parameters under investigation were not affected by either low or high glycaemic indices . The present systematic review and meta- analysis provides evidence of a beneficial effect of a low glycaemic index/load diet in children and adolescents being either overweight or obese . Regarding the limitations of this analysis , further studies adopting a homogenous design are necessary to assure the present findings . Since low glycaemic index/load regimens were not associated with a deterioration of the outcome parameters , these diets should not be categorically excluded when looking for alternatives to change lifestyle habits in this age group	[ "Some studies focused on the effect of the dietary glycemic index on lipoproteins and apolipoproteins in adults ; however , little evidence exists among adolescents regarding the effect of a low glycemic index ( LGI ) diet on apolipoproteins and lipoprotein ( a ) ( Lpa ) . This study was conducted to evaluate the effect of an LGI diet on the lipid profile , apolipoproteins and Lpa among overweight and obese adolescent girls . For this parallel design ed r and omized clinical trial , 50 healthy overweight/obese girls at pubertal ages were r and omly allocated to an LGI or a healthy nutritional recommendations ( HNR ) based diet . Equal macronutrient distributed diets were prescribed to both groups . Biochemical measurements included lipid profile , apolipoprotein A , apolipoprotein B and Lpa were conducted before and after 10 weeks of intervention . Forty one adolescent girls completed the study . The dietary glycemic index in the LGI group was 42.67 ± 0.067 . There were no differences in the mean of blood lipid indices baseline and after intervention between two groups . There were no significant differences between the two groups regarding lipid profiles , apolipoproteins and Lpa . There were no significant differences in lipid profiles , apolipoproteins and Lpa between the LGI diet and the HNR-based diet and the impact of these two diets on lipid profile was equal in this trial . Trial registry code : I RCT 201109272839N4", "The determine the effect of different foods on the blood glucose , 62 commonly eaten foods and sugars were fed individually to groups of 5 to 10 healthy fasting volunteers . Blood glucose levels were measured over 2 h , and expressed as a percentage of the area under the glucose response curve when the same amount of carbohydrate was taken as glucose . The largest rises were seen with vegetables ( 70 + /- 5 % ) , followed by breakfast cereals ( 65 + /- 5 % ) , cereals and biscuits ( 60 + /- 3 % ) , fruit ( 50 + /- 5 % ) , dairy products ( 35 + /- 1 % ) , and dried legumes ( 31 + /- 3 % ) . A significant negative relationship was seen between fat ( p less than 0.01 ) and protein ( p less than 0.001 ) and postpr and ial glucose rise but not with fiber or sugar content", "BACKGROUND The possible advantage for weight loss of a diet that emphasizes protein , fat , or carbohydrates has not been established , and there are few studies that extend beyond 1 year . METHODS We r and omly assigned 811 overweight adults to one of four diets ; the targeted percentages of energy derived from fat , protein , and carbohydrates in the four diets were 20 , 15 , and 65 % ; 20 , 25 , and 55 % ; 40 , 15 , and 45 % ; and 40 , 25 , and 35 % . The diets consisted of similar foods and met guidelines for cardiovascular health . The participants were offered group and individual instructional sessions for 2 years . The primary outcome was the change in body weight after 2 years in two-by-two factorial comparisons of low fat versus high fat and average protein versus high protein and in the comparison of highest and lowest carbohydrate content . RESULTS At 6 months , participants assigned to each diet had lost an average of 6 kg , which represented 7 % of their initial weight ; they began to regain weight after 12 months . By 2 years , weight loss remained similar in those who were assigned to a diet with 15 % protein and those assigned to a diet with 25 % protein ( 3.0 and 3.6 kg , respectively ) ; in those assigned to a diet with 20 % fat and those assigned to a diet with 40 % fat ( 3.3 kg for both groups ) ; and in those assigned to a diet with 65 % carbohydrates and those assigned to a diet with 35 % carbohydrates ( 2.9 and 3.4 kg , respectively ) ( P>0.20 for all comparisons ) . Among the 80 % of participants who completed the trial , the average weight loss was 4 kg ; 14 to 15 % of the participants had a reduction of at least 10 % of their initial body weight . Satiety , hunger , satisfaction with the diet , and attendance at group sessions were similar for all diets ; attendance was strongly associated with weight loss ( 0.2 kg per session attended ) . The diets improved lipid-related risk factors and fasting insulin levels . CONCLUSIONS Reduced-calorie diets result in clinical ly meaningful weight loss regardless of which macronutrients they emphasize . ( Clinical Trials.gov number , NCT00072995 .", "OBJECTIVE This study examined the relation between quality of dietary carbohydrate intake , as measured by glycemic index ( GI ) and glycemic load ( GL ) , and serum high-sensitivity C-reactive protein ( hs-CRP ) levels . METHODS During a 1-y observational study , data were collected at baseline and at each quarter thereafter . GI and GL were calculated from multiple 24-h dietary recalls ( 24HRs ) , 3 r and omly selected 24HRs at every quarter , with up to 15 24HRs per participant . The hs-CRP was measured in blood sample s collected at baseline and each of the four quarterly measurement points . Multivariable linear mixed models were used to examine the cross-sectional and longitudinal associations of GI , GL , and hs-CRP . RESULTS Among 582 adult men and women with at least two measurements of diet and hs-CRP , average daily GI score ( white bread = 100 ) was 85 and average GL was 198 , and average hs-CRP was 1.84 mg/L. Overall , there was no association between GI or GL and hs-CRP . Subgroup analyses revealed an inverse association between GL and hs-CRP among obese individuals ( body mass index > or = 30 kg/m(2 ) ) . CONCLUSION Quality of dietary carbohydrates does not appear to be associated with serum hs-CRP levels . Among obese individuals , higher dietary GL appears to be related to lower hs-CRP levels . Due to the limited number of studies on this topic and their conflicting results , further investigation is warranted", "BACKGROUND Fatty liver is highly prevalent among obese children and represents a major risk factor for chronic liver diseases and severe metabolic complications . METHODS We r and omly assigned 17 obese children 8 - 17 years of age with fatty liver to either an experimental low-glycemic-load or conventional low-fat diet for 6 months . Participants in both groups received nutrition education and behavioral counseling of equal intensity . The primary outcome was hepatic lipid content measured by proton magnetic resonance spectroscopy . Secondary outcomes included change in visceral fat , BMI , anthropometrics , alanine aminotransferase ( ALT ) , and insulin resistance . RESULTS A total of 16 participants completed the study . Reported glycemic load decreased in the low-glycemic-load group and reported dietary fat decreased in the low-fat group . At baseline , liver fat was 23.8 % [ st and ard deviation ( SD ) 12.2 ] in the low-glycemic-load group and 29.3 % ( 14.1 ) in the low-fat group . Liver fat decreased substantially in both groups at 6 months expressed as absolute percentage change , with no between-group differences [ -8.8 ( st and ard error ( SE ) 4.1 ) vs. -10.5 (3.7)% , respectively , p=0.76 for group × time interaction ] . Secondary outcomes also improved on both diets , with no between-group differences . Baseline and change in ALT were strongly associated with hepatic fat content . CONCLUSIONS Weight-reducing diets focused either on glycemic load or dietary fat improved hepatic steatosis over 6 months . Additional research is needed to determine whether these diets differ in effectiveness over the long term . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00480922", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "OBJECTIVE To test the utility of homeostasis model assessment ( HOMA ) in predicting insulin sensitivity [ x10(- 4 ) min(-1)/(microIU/ml ) ] in children and to develop and compare two new prediction equations for insulin sensitivity in children using demographic and anthropometric measures in the presence or absence of fasting insulin . RESEARCH DESIGN AND METHODS We studied 156 white and African-American children with complete data ( mean age 9.7 + /- 1.8 years , 87.8 % Tanner Stage 1 or 2 ) . For development of new equations , two-thirds of the children were r and omly assigned to a development group , whereas the remaining children were assigned to a cross-validation group . RESULTS A modified HOMA equation accurately predicted insulin sensitivity , but its utility is similar to fasting insulin alone . Demographic and anthropometric measures alone did not predict insulin sensitivity accurately , even when precise measures of body composition were included in the prediction model . Ethnicity , calf skinfold , and fasting insulin together explained 73 % of the variance in insulin sensitivity and accurately predicted insulin sensitivity . The regression of measured versus predicted insulin sensitivity in the cross-validation group was not significantly different from the line of identity ( P > 0.05 ) . Mean difference between measured and predicted insulin sensitivity was also not significant ( P > 0.05 ) . Some bias was apparent , particularly in white boys . CONCLUSIONS Ethnicity , calf skinfold , and fasting insulin can accurately predict insulin sensitivity with greater precision than HOMA or fasting insulin alone ( R(2 ) = 0.73 ) . Future studies , however , are needed to examine whether a universal equation is possible . A cross-vali date d prediction equation may be useful in population -based studies when complex measures of insulin sensitivity are not available", "Background The role of a low glycemic index ( GI ) diet in the management of adolescent obesity remains controversial . In this study , we aim to evaluate the impact of low GI diet versus a conventional Chinese diet on the body mass index ( BMI ) and other obesity indices of obese adolescents . Methods Obese adolescents aged 15–18 years were identified from population -recruited , territory-wide surveys . Obesity was defined as BMI ≥95th percentile of Hong Kong local age- and sex-specific references . Eligible subjects were r and omized to either an intervention with low GI diet ( consisting of 45 - 50 % carbohydrate , 30 - 35 % fat and 15 - 20 % protein ) or conventional Chinese diet as control ( consisting of 55 - 60 % carbohydrate , 25 - 30 % fat and 10 - 15 % protein ) . We used r and om intercept mixed effects model to compare the differential changes across the time points from baseline to month 6 between the 2 groups . Results 104 obese adolescents were recruited ( 52 in low GI group and 52 in control group ; 43.3 % boys ) . Mean age was 16.7 ± 1.0 years and 16.8 ±1.0 years in low GI and control group respectively . 58.7 % subjects completed the study at 6 months ( 65.4 % in low GI group and 51.9 % in control group ) . After adjustment for age and sex , subjects in the low GI group had a significantly greater reduction in obesity indices including BMI , body weight and waist circumference ( WC ) compared to subjects in the control group ( all p levels , WC was found to be significantly lower in the low GI group compared to the conventional group ( p = 0.018 ) . Conclusion Low GI diet in the context of a comprehensive lifestyle modification program may be an alternative to conventional diet in the management of obese adolescents . Trial registration number Clinical Trials.gov Ref . No :", "OBJECTIVE To examine prospect ively the relationship between glycemic diets , low fiber intake , and risk of non-insulin-dependent diabetes mellitus . DESIGN Cohort study . SETTING In 1986 , a total of 65173 US women 40 to 65 years of age and free from diagnosed cardiovascular disease , cancer , and diabetes completed a detailed dietary question naire from which we calculated usual intake of total and specific sources of dietary fiber , dietary glycemic index , and glycemic load . MAIN OUTCOME MEASURE Non-insulin-dependent diabetes mellitus . RESULTS During 6 years of follow-up , 915 incident cases of diabetes were documented . The dietary glycemic index was positively associated with risk of diabetes after adjustment for age , body mass index , smoking , physical activity , family history of diabetes , alcohol and cereal fiber intake , and total energy intake . Comparing the highest with the lowest quintile , the relative risk ( RR ) of diabetes was 1.37 ( 95 % confidence interval [ CI ] , 1.09 - 1.71 , P trend=.005 ) . The glycemic load ( an indicator of a global dietary insulin dem and ) was also positively associated with diabetes ( RR= 1.47 ; 95 % CI , 1.16 - 1.86 , P trend=.003 ) . Cereal fiber intake was inversely associated with risk of diabetes when comparing the extreme quintiles ( RR=0.72 , 95 % CI , 0.58 - 0.90 , P trend=.001 ) . The combination of a high glycemic load and a low cereal fiber intake further increased the risk of diabetes ( RR=2.50 , 95 % CI , 1.14 - 5.51 ) when compared with a low glycemic load and high cereal fiber intake . CONCLUSIONS Our results support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of diabetes in women . Further , they suggest that grains should be consumed in a minimally refined form to reduce the incidence of diabetes", "Childhood obesity is associated with an increased carotid intima-media thickness ( IMT ) and stiffness . Increased carotid wall thickening and rigidity are considered markers of sub clinical atherosclerosis . The aim of the present study was to test the effect of two hypocaloric diets of varying glycemic index on weight loss and markers of sub clinical atherosclerosis in obese children . Seventy consecutive obese children attending the Outpatient Weight Clinic of the Department of Pediatrics were invited to participate in an intensive dietary protocol . Twenty-six accepted and were r and omly assigned to two different groups : the first group followed a hypocaloric low-glycemic index diet and the second a hypocaloric high-glycemic index diet . Anthropometric measures and biochemical tests were performed in all children . Quantitative B-mode ultrasound scans were used to measure intima-media thickness ( IMT ) and diameters of the common carotid artery . Considering both groups together , at 6 months , body mass index decreased from 28.3 ± 3.1 to 25.8 ± 3.3 kg/m2 , systolic blood pressure from 119 ± 12 to 110 ± 11 mmHg ( P 0.001 ) , diastolic blood pressure from 78 ± 8 to 74 ± 7 mmHg ( P 0.001 ) , IMT from 0.48 ± 0.05 to 0.43 ± 0.07 mm ( P ) , stiffness from 3.57 ± 1.04 to 2.98 ± 0.94 mm ( P = 0.002 ) , and high-sensitivity C-reactive protein from 1.5 ± 0.9 ( values log transformed ) to 0.4 ± 1.1 ( P in fasting serum triglycerides , total cholesterol , and high-density lipoprotein cholesterol . Insulin resistance ( calculated by the HOmeostatic Model Assessment index [ HOMA ] score ) significantly reduced only in the low-glycemic-index diet group ( P on carotid IMT and stiffness in obese children and demonstrates , for the first time , an amelioration of insulin sensitivity in obese children after a low-glycemic index diet . These results justify the advice to obese children to follow a low-glycemic index diet in order to improve their cardiometabolic profile ", "OBJECTIVES To compare insulin sensitivity and pancreatic beta-cell function measured by the euglycemic and the hyperglycemic clamp , with simple estimates of insulin sensitivity and pancreatic beta-cell function in youth . Study design We measured insulin sensitivity with a euglycemic clamp and first- and second-phase insulin secretion with a hyperglycemic clamp in 156 AA and white youths . Estimates of insulin sensitivity ( fasting insulin level [ I(F ) ] , the ratio of fasting glucose [ G(F ) ] to I(F ) [ G(F)/I(F ) ] , homeostasis model assessment estimate of insulin sensitivity [ HOMA IS ] , and quantitative insulin sensitivity check index [ QUICKI ] ) and estimates of pancreatic beta-cell function ( I(F ) , the ratio of I(F ) to G(F ) [ I(F)/G(F ) ] , and homeostasis model assessment estimate of pancreatic beta-cell function [ HOMA % B ] ) were derived from fasting measurements . RESULTS In the total group , IS(Eu ) correlated strongly with I(F ) ( r=-0.92 ) , G(F)/I(F ) ( r=0.92 ) , HOMA IS ( r=0.91 ) , and QUICKI ( r=0.91 ) ( P First-phase and second-phase insulin secretion correlated with I(F ) , I(F)/G(F ) , and HOMA % B ( first-phase insulin secretion : r=0.76 , 0.79 , 0.82 ; second-phase insulin secretion : r=0.83 , 0.86 , 0.86 , respectively ; P children with impaired glucose tolerance and type 2 diabetes mellitus remains to be determined", "Dietary strategies to improve early cardiovascular markers in overweight children are needed . We investigated the effect of dietary protein and glycemic index ( GI ) on cardiovascular markers and metabolic syndrome ( MetS ) scores in 5- to 18-y-old children of overweight/obese parents from 8 European centers . Families were r and omized to 1 of 5 diets consumed ad libitum : high protein ( HP ) or low protein ( LP ) combined with high GI ( HGI ) or low GI ( LGI ) , or a control diet . At 6 centers , families received dietary instruction ( instruction centers ) ; at 2 centers , free foods were also provided ( supermarket centers ) . Diet , anthropometry , blood pressure , and serum cardiovascular markers ( lipid profile , glucose regulation , and inflammation ) were measured in 253 children at baseline , 1 mo , and /or 6 mo . Protein intake was higher in the HP groups ( 19.9 ± 1.3 % energy ) than in the LP groups at 6 mo ( 16.8 ± 1.2 % energy ) ( P = 0.001 ) . The GI was 4.0 points lower ( 95 % CI : 2.1 , 6.1 ) in the LGI compared with the HGI groups ( P in protein intake than did the groups in the instruction centers ( P = 0.009 ) , indicating better compliance . The HP diets evoked a 2.7-cm ( 95 % CI : 0.9 , 5.1 ) smaller waist circumference and a 0.25-mmol/L ( 95 % CI : 0.09 , 0.41 ) lower serum LDL cholesterol compared with the LP diets at 6 mo ( P the HP compared with LP diets reduced waist circumference ( P = 0.004 ) , blood pressure ( P serum insulin ( P = 0.013 ) , and homeostasis model of assessment -insulin resistance ( P = 0.016 ) . In the instruction centers , the HP compared with the LP diets reduced LDL cholesterol ( P = 0.004 ) . No consistent effect of GI was seen and the MetS scores were not affected . In conclusion , increased protein intake improved cardiovascular markers in high-risk children , particularly in those undergoing most intensive intervention", "OBJECTIVE Intake of carbohydrates that provide a large glycemic response has been hypothesized to increase the risk of NIDDM , whereas dietary fiber is suspected to reduce incidence . These hypotheses have not been evaluated prospect ively . RESEARCH DESIGN AND METHODS We examined the relationship between diet and risk of NIDDM in a cohort of 42,759 men without NIDDM or cardiovascular disease , who were 40–75 years of age in 1986 . Diet was assessed at baseline by a vali date d semiquantitative food frequency question naire . During 6-years of follow-up , 523 incident cases of NIDDM were documented . RESULTS The dietary glycemic index ( an indicator of carbohydrate 's ability to raise blood glucose levels ) was positively associated with risk of NIDDM after adjustment for age , BMI , smoking , physical activity , family history of diabetes , alcohol consumption , cereal fiber , and total energy intake . Comparing the highest and lowest quintiles , the relative risk ( RR ) of NIDDM was 1.37 ( 95 % CI , 1.02–1.83 , P trend = 0.03 ) . Cereal fiber was inversely associated with risk of NIDDM ( RR = 0.70 ; 95 % CI , 0.51–0.96 , P trend = 0.007 ; for > 8.1 g/day vs. glycemic load and a low cereal fiber intake further increased the risk of NIDDM ( RR = 2.17 , 95 % CI , 1.04–4.54 ) when compared with a low glycemic load and high cereal fiber intake . CONCLUSIONS These findings support the hypothesis that diets with a high glycemic load and a low cereal fiber content increase risk of NIDDM in men . Further , they suggest that grains should be consumed in a minimally refined form to reduce the incidence of NIDDM ", "OBJECTIVE To compare the effectiveness and safety of carbohydrate (CHO)-modified diets with a st and ard portion-controlled ( PC ) diet in obese children . STUDY DESIGN Obese children ( n=102 ) aged 7 - 12 years were r and omly assigned to a 3-month intervention of a low-CHO ( LC ) , reduced glycemic load ( RGL ) , or st and ard PC diet , along with weekly dietary counseling and biweekly group exercise . Anthropometry , dietary adherence , and clinical measures were evaluated at baseline and 3 , 6 , and 12 months . Analyses applied intention-to-treat longitudinal mixed models . RESULTS Eighty-five children ( 83 % ) completed the 12-month assessment . Daily caloric intake decreased from baseline to all time points for all diet groups ( P months , body mass index z score was lower in all diet groups ( LC , -0.27 ± 0.04 ; RGL , -0.20 ± 0.04 ; PC , -0.21 ± 0.04 ; P for waist circumference and percent body fat . At 12 months , participants in all diet groups had lower body mass index z scores than at baseline ( LC , -0.21 ± 0.04 ; RGL , -0.28 ± 0.04 ; PC , -0.31 ± 0.04 ; P lower percent body fat , but no reductions in waist circumference were maintained . All diets demonstrated some improved clinical measures . CONCLUSION Diets with modified CHO intake were as effective as a PC diet for weight management in obese children . However , the lower adherence to the LC diet suggests that this regimen is more difficult for children to follow , particularly in the long term", "OBJECTIVE : To investigate the effect of protein and glycemic index ( GI ) on body composition among European children in the r and omized , 6-month dietary intervention DiOGenes ( diet , obesity , and genes ) family-based study . PATIENTS AND METHODS : In the study , 827 children ( 381 boys and 446 girls ) , aged 5 to 18 years , completed baseline examinations . Families with parents who lost ≥8 % of their weight during an 8-week run-in low-calorie diet period were r and omly assigned to 1 of 5 ad libitum diets : low protein (LP)/low glycemic index ( LGI ) ; LP/high GI ( HGI ) ; high protein (HP)/LGI ; HP/HGI ; and control diet . The target difference was 15 GI U between the LGI/HGI groups and 13 protein percentage points between the LP/HP groups . There were 658 children examined after 4 weeks . Advice on food-choice modification was provided at 6 visits during this period . No advice on weight loss was provided because the focus of the study was the ability of the diets to affect outcomes through appetite regulation . Anthropometric measurements and body composition were assessed at baseline , week 4 , and week 26 . RESULTS : In the study , 465 children ( 58.1 % ) completed all assessment s. The achieved differences between the GI and protein groups were 2.3 GI U and 4.9 protein percentage points , respectively . The LP/HGI group increased body fat percentage significantly more than the other groups ( P = .040 ; partial η2 = 0.039 ) , and the percentage of overweight/obese children in the HP/LGI group decreased significantly during the intervention ( P = .031 ) . CONCLUSIONS : Neither GI nor protein had an isolated effect on body composition . However , the LP/HGI combination increased body fat , whereas the HP/LGI combination was protective against obesity in this sample of children", "BACKGROUND The incidence of type 2 diabetes increases markedly for obese children after puberty . However , the effect of dietary composition on body weight and diabetes risk factors has not been studied in adolescents . OBJECTIVE To compare the effects of an ad libitum , reduced-glycemic load ( GL ) diet with those of an energy-restricted , reduced-fat diet in obese adolescents . DESIGN R and omized control trial consisting of a 6-month intervention and a 6-month follow-up . MAIN OUTCOME MEASURES Body composition ( body mass index [ BMI ; calculated as weight in kilograms divided by the square of height in meters ] and fat mass ) and insulin resistance ( homeostasis model assessment ) were measured at 0 , 6 , and 12 months . Seven-day food diaries were used as a process measure . SUBJECTS Sixteen obese adolescents aged 13 to 21 years . Intervention Experimental ( reduced-GL ) treatment emphasized selection of foods characterized by a low to moderate glycemic index , with 45 % to 50 % of energy from carbohydrates and 30 % to 35 % from fat . In contrast , conventional ( reduced-fat ) treatment emphasized selection of low-fat products , with 55 % to 60 % of energy from carbohydrates and 25 % to 30 % from fat . RESULTS Fourteen subjects completed the study ( 7 per group ) . The GL decreased significantly in the experimental group , and dietary fat decreased significantly in the conventional group ( P /- SEM BMI ( -1.3 + /- 0.7 vs 0.7 + /- 0.5 ; P = .02 ) and fat mass ( -3.0 + /- 1.6 vs 1.8 + /- 1.0 kg ; P = .01 ) had decreased more in the experimental compared with the conventional group , differences that were material ly unchanged in an intention-to-treat model ( n = 16 ) ( BMI , P = .02 ; fat mass , P = .01 ) . Insulin resistance as measured by means of homeostasis model assessment increased less in the experimental group during the intervention period ( -0.4 + /- 0.9 vs 2.6 + /- 1.2 ; P = .02 ) . In post hoc analyses , GL was a significant predictor of treatment response among both groups ( R2 = 0.51 ; P = .006 ) , whereas dietary fat was not ( R2 = 0.14 ; P = .22 ) . CONCLUSIONS An ad libitum reduced-GL diet appears to be a promising alternative to a conventional diet in obese adolescents . Large-scale r and omized controlled trials are needed to further evaluate the effectiveness of reduced-GL and -glycemic index diets in the treatment of obesity and prevention of type 2 diabetes", "OBJECTIVE To evaluate the efficacy and safety of a carbohydrate restricted versus a low fat diet on weight loss , metabolic markers , body composition , and cardiac function tests in severely obese adolescents . STUDY DESIGN Subjects were r and omly assigned to 1 of 2 diets : a high protein , low carbohydrate ( 20 g/d ) diet ( high protein , low carbohydrate , HPLC ) or low fat ( 30 % of calories ) regimen for 13 weeks ; close monitoring was maintained to evaluate safety . After the intervention , no clinical contact was made until follow-up measurements were obtained at 24 and 36 weeks from baseline . The primary outcome was change in body mass index Z-score for age and sex ( BMI -Z ) at 13 , 24 , and 36 weeks . RESULTS Forty-six subjects ( 24 HPLC , 22 in low fat ) initiated and 33 subjects completed the intervention ; follow-up data were available on approximately half of the subjects . Significant reduction in ( BMI -Z ) was achieved in both groups during intervention and was significantly greater for the HPLC group ( P = .03 ) . Both groups maintained significant BMI -Z reduction at follow-up ; changes were not significantly different between groups . Loss of lean body mass was not spared in the HPLC group . No serious adverse effects were observed related to metabolic profiles , cardiac function , or subjective complaints . CONCLUSIONS The HPLC diet is a safe and effective option for medically supervised weight loss in severely obese adolescents", "BACKGROUND In Hispanic children and adolescents , the prevalence of obesity and insulin resistance is considerably greater than in non-Hispanic white children . A low-glycemic load diet ( LGD ) has been proposed as an effective dietary intervention for pediatric obesity , but to our knowledge , no published study has examined the effects of an LGD in obese Hispanic children . OBJECTIVE We compared the effects of an LGD and a low-fat diet ( LFD ) on body composition and components of metabolic syndrome in obese Hispanic youth . DESIGN Obese Hispanic children ( 7 - 15 y of age ) were r and omly assigned to consume an LGD or an LFD in a 2-y intervention program . Body composition and laboratory assessment s were obtained at baseline and 3 , 12 , and 24 mo after intervention . RESULTS In 113 children who were r and omly assigned , 79 % of both groups completed 3 mo of treatment ; 58 % of LGD and 55 % of LFD subjects attended 24-mo follow-up . Compared with the LFD , the LGD decreased the glycemic load per kilocalories of reported food intakes in participants at 3 mo ( P = 0.02 ) . Both groups had a decreased BMI z score ( P waist circumference and systolic blood pressure ( P changes in BMI , insulin resistance , or components of metabolic syndrome ( all P > 0.5 ) . CONCLUSIONS We showed no evidence that an LGD and an LFD differ in efficacy for the reduction of BMI or aspects of metabolic syndrome in obese Hispanic youth . Both diets decreased the BMI z score when prescribed in the context of a culturally adapted , comprehensive weight-reduction program" ]	41189bae-06ff-11f0-808a-c43d1ab1c353
Zinc is a mineral that plays a vital role in many biological processes and plays an important role in insulin action and carbohydrate metabolism . It may also have a protective role in the prevention of atherogenesis . Numerous studies have evaluated the effects of Zinc supplementation on serum lipids in humans and have demonstrated varying results . We systematic ally evaluated the literature and performed a meta- analysis on the effects of Zinc supplementation on serum lipids . A five staged comprehensive search of the literature was conducted in the following data bases ; PubMed , Web of Science and SciVerse Scopus for studies published before 31st December 2014 . All controlled clinical trial in humans , that included a Zinc supplement intervention , either alone or in combination with other micronutrients and evaluated effects on serum lipids ( total cholesterol [ TC ] , triglycerides [ TG ] , LDL cholesterol [ LDL-c ] and HDL cholesterol [ HDL-c ] ) . A meta- analysis of selected studies was performed using RevMan v5.3 . The Jaded scale was used to assess the method ological quality of the trials included in the systematic review . A total of 24 studies were included in Meta analysis , which included a total of 33 Zinc interventions , in a total of 14,515 participants in the Zinc intervention or control group . The duration of Zinc supplementation ranged from 1 month to 7.5 years . The dose of elemental Zinc supplemented ranged from 15–240 mg/day . The pooled mean difference for TC between Zinc supplemented and placebo groups from r and om effects analysis was −10.92 mg/dl ( 95 % CI : −15.33 , −6.52 ; p while for HDL cholesterol it was 2.12 mg/dl ( 95 % CI : −0.74 , 4.98 ; p = 0.15 , I2 = 83 % ) . The pooled mean difference for LDL-c between Zinc supplemented and placebo group from r and om effect analysis was −6.87 mg/dl ( 95 % CI : −11.16,-2.58 ; p ) and for TG it was −10.92 mg/dl ( 95 % CI : −18.56 , − 3.28 ; p conclusion , Zinc supplementation has favourable effects on plasma lipid parameters . Zinc supplementation significantly reduced total cholesterol , LDL cholesterol and triglycerides . Therefore it may have the potential to reduce the incidence of atherosclerosis related morbidity and mortality	[ "Aims : To evaluate the effects of zinc with or without other antioxidants on blood glucose , lipid profile , and serum creatinine in adult diabetics on long-term follow-up . Material s and methods : Patients ( n = 96 ) were r and omly allocated to three groups : group A ( n = 29 ) was supplemented with oral zinc sulfate ( 22 mg/day ) and multivitamin/mineral ( zinc+MVM ) preparation ; group B ( n = 31 ) was given the same preparation without zinc ( MVM ) ; and group C ( n = 36 ) was given a matching placebo for a period of 4 months in a single-blinded study . Blood sample s were taken at baseline and after 4 months of supplementation to assess blood glucose ( fasting and postpr and ial ) and glycosylated hemoglobin ( HbA1C% ) and serum levels of zinc , creatinine , and lipids . Results : The zinc+MVM group had a mean change of fasting blood sugar −0.33 mmol/L ( st and ard error of the mean 0.21 mmol/L ) and was significant ( P = 0.05 ) when compared with the other two groups ( mean change in the MVM group + 0.19 ( 0.31 ) mmol/L and + 0.43 ( 0.23 ) mmol/L in the control group , respectively ) . The HbA1C% level reduced significantly , irrespective of the baseline level , in zinc+MVM-supplemented individuals . In the other two groups , the change of HbA1C% level was not significant . Serum lipid levels reduced significantly in the zinc+MVM and MVM groups . Conclusions : Zinc+MVM supplementation showed beneficial effects in the metabolic control of adult diabetics in addition to elevating their serum zinc level . Zinc supplementation improved glycemic control measured by HbA1C% and fasting and postpr and ial glucose . Furthermore , zinc supplementation lowered serum cholesterol and cholesterol/high-density lipoprotein ratio ", "Objective : To evaluate the effect of oral administration of selenium and zinc tablets in patients with cancer of the digestive tract during chemotherapy . Design : A case – control , r and omized study . Setting : Medical Oncology , II University of Naples , Naples , Italy . Subjects : A total of 60 patients ( median age 55 y , range 46–61 y ) with diagnosis of gut cancer were r and omized in 1999 . Patients were treated for 60 days with chemotherapy . Interventions : Trace elements were measured by atomic absorption spectroscopy . The nutritional status of the patients was assessed by biochemical and bio-impedance analysis ( BIA ) parameters in basal condition and after 60 days of treatment . Oral administration of selenium and zinc in oral tablet form for 50 days was Se 200 μg/day ( 50 μg/tablet ) and Zn 21 mg/day ( 7 mg/tablet ) . Results : Both in the basal condition and at 60 days all patients were malnourished . Selenium and zinc concentrations were significantly lower ( P whereas copper concentration was significantly higher ( P further worsening of nutritional status and experienced a significant decrease of asthenia with an increase of appetite . On the other h and , 24/30 ( 80 % ) untreated patients had a significant decline of all parameters studied after 60 days ( prealbumin , cholesterol , transferrin , P total proteins , albumin/globulin ratio , P fat-free mass , fat mass , Na+/K+ ratio , body mass index P fat free mass/fat mass , total body water , extra cellular/intra cellular water , basal metabolic rate : P that Se and Zn supplementation may improve the clinical course of general conditions in patients with gut cancer . These effects of Se and Zn require confirmation in an independent trial of appropriate design before new public health recommendations regarding Se and Zn supplementation can be made . European Journal of Clinical Nutrition ( 2001 ) 55 ,", "UNLABELLED Purpose : The aim of this study was to assess the effects of zinc supplementation on anthropometric measures , improving lipid profile biomarkers , and fasting blood glucose level in obese people . METHODS This r and omized , double- blind clinical trial was carried out on 60 obese participants in the 18 - 45 age range for one month . The participants were r and omly divided into the intervention group , who received 30 mg/d zinc gluconate , and the placebo group who received 30mg/d starch . Anthropometric measurements ( body mass index ( BMI ) , weight and waist circumference ) were recorded before and at the end of study . Lipid profile biomarkers and fasting blood glucose were determined using enzymatic procedure . Analysis of Covariance ( ANCOVA ) test was run to compare the post-treatment values of the two groups , and t-test was conducted to compare within group changes . RESULTS Serum zinc concentration was increased significantly in intervention group ( p=0.024 ) . BMI and body weight was significantly decreased ( p=0.030 and p=0.020 , respectively ) . Lipid profile biomarkers and fating blood glucose did not change significantly but triglyceride level was significantly decreased ( p=0.006 ) in the intervention group . CONCLUSION The obtained results indicate that zinc supplementation improves BMI , body weight , and triglyceride concentration without considerable effects on lipid profile and glucose level . Zinc can be suggested as a suitable supplementation therapy for obese people , but more studies are needed to verify the results", "Antioxidant micronutrients have been reported to be associated with an improvement in the blood profile , but the results are not consistent . The aim of the present study was to assess the effects of antioxidant supplementation on changes in the serum lipid profile of adult participants in the SU.VI.MAX study . French adults ( n=12,741∶7,713 females aged 35–60 yr , and 5,028 males aged 45–60 yr ) received daily antioxidant supplementation ( 120 mg vitamin C , 30 mg vitamin E , 6 mg β-carotene , 100 μg selenium , and 20 mg zinc ) or a matching placebo . Median follow-up time was 7.5 yr . After 7.5 yr , no effect of supplementation on total cholesterol was observed in men or women after adjusting for baseline total cholesterol levels and lipid-lowering medications . The prevalence of hypercholesterolemia ( ≥6.5 mmol/L ) showed a trend toward being higher in women who received supplements compared with those who received the placebo ( P=0.06 ) . In both sexes , the group receiving supplements exhibited higher mean serum TG concentrations than did the placebo group ( P=0.06 in men ; P=0.05 in women ) . The prevalence of hypertriglyceridemia ( ≥2.3 mmol/L ) was also significantly higher in men who received supplements ( P=0.03 ) , but not in women . Our results suggest than long-term daily supplementation with low doses of β-carotene , vitamins C and E , selenium , and zinc does not result in an improved lipid profile and could even adversely affect some blood lipids , possibly with a higher risk of hyperlipidemia in women", "One hundred and three apparently healthy elderly subjects age 60 - 89 y were r and omly assigned to one of three treatments : placebo , 15 mg zinc/d , or 100 mg Zn/d for 3 mo . Plasma Zn was significantly increased only in the 100 mg Zn group . Zn concentrations in erythrocytes , platelets , mononuclear cells , and polymorphonuclear leukocytes were not significantly increased by any treatment . None of the treatments significantly altered delayed dermal hypersensitivity ( DDH ) to a panel of seven recall antigens or in vitro lymphocyte proliferative responses ( LPR ) to mitogens and antigens . Fifteen subjects had initially poor lymphocyte proliferative responses that improved in 14 of these individuals during the study ; this was not due to Zn supplementation but might have been caused by one or more components of a vitamin-mineral supplement administered to all study subjects", "The recent report by Hooper PL , et al. ( JAMA 1980;244:1960 - 1 ) that pharmacological doses ( 160 mg ) of zinc lowered high-density lipoprotein (HDL)-cholesterol in men and that zinc might be an atherogenic agent prompted this report of the effect of zinc supplementation on HDL-cholesterol in women . Four levels of zinc supplements ( 0 , 15 , 50 , or 100 mg/day ) were given to 32 women for 8 wk . Fasting plasma HDL-cholesterol and zinc were measured at biweekly intervals . Plasma zinc increased in the supplemented groups , peaked at wk 4 , then decreased toward initial values . The decline in plasma zinc regardless of continuing zinc administration may reflect a homeostatic response . No significant differences were seen in HDL-cholesterol over the 8 wk except in the 100 mg group at wk 4 when a transient decrease , -8.4 % ( 57 to 48 mg/dl , p less than 0.04 ) was observed . Thus we conclude that in women the reduction in HDL-cholesterol in response to the pharmacological doses of zinc used in this study was transient and not dose-related", "A 12-wk double-blind study was conducted to determine the effect of oral zinc supplementation upon serum total cholesterol , lipoprotein-cholesterol fractions , and serum triglycerides in white males . The subjects were r and omly assigned to one of three treatment groups and consumed either a placebo tablet ( n = 9 ) , 50 mg Zn/d ( n = 13 ) , or 75 mg Zn/d ( n = 9 ) as Zn gluconate . Serum total cholesterol , low-density-lipoprotein ( LDL ) cholesterol , very-low-density-lipoprotein ( VLDL ) cholesterol , and triglycerides were not affected by Zn supplements . However , serum high-density-lipoprotein (HDL)-cholesterol levels in subjects assigned to the 75 mg Zn/d group were significantly lower at weeks 6 and 12 than those for the placebo group and lower at weeks 6 , 8 , and 12 than at baseline ; subjects assigned to the 50 mg Zn/d group had lower serum HDL-cholesterol levels at week 12 than did the placebo group and lower at week 12 than at base line", "The effects of long-term supplementation with pharmacologic doses of zinc oxide on serum levels of zinc , lipids and hematocrit have not been studied systematic ally to date . Eleven Clinical Centers enrolled 4757 participants from 1992 to 1998 as part of the Age-Related Eye Disease Study ( AREDS ) . Of these , 3640 participants , aged 55 - 80 y , who had early-to-late age-related macular degeneration ( AMD ) were r and omly assigned to daily supplementation with or without 80 mg of zinc as zinc oxide plus 2 mg of copper as cupric oxide to study the effects of zinc supplementation on the progression to late AMD . This paper reports on the effect of a 5-y supplementation with zinc oxide and cupric oxide on serum zinc , copper , lipids , and hematocrit for 717 participants from three clinical centers . At the 5-y exam , the median increase in serum zinc levels for participants assigned to zinc formulations was 17 % compared with a 2 % increase for participants not assigned to zinc ( P serum zinc was observed at 1 y and remained fairly constant over the 5-y period . After 5 y , no significant differences in changes in serum hematocrit , copper or lipids were found between participants assigned to formulations containing zinc and copper , and those assigned to formulations without zinc and copper . Estimates from a modified Block Food-Frequency Question naire suggest the AREDS population at baseline had a zinc intake from diet similar to that of the general population", "Background and Aims : Patients on maintenance hemodialysis ( HD ) face an increased risk of atherosclerosis , a crucial problem and the leading cause of cardiovascular morbidity and mortality . This study was design ed to evaluate the effects of zinc supplementation on paraoxonase ( PON ) enzyme activity in patients on HD . Methods : This double-blind r and omized controlled trial was conducted from June 2005 to June 2007 . Sixty HD patients were enrolled and divided into two groups : treatment ( case ) and control . The treatment and control groups were treated with 100 mg/day zinc or placebo , respectively , for 2 months . Serum zinc concentration was measured by atomic absorption spectrophotometry . PON activity was evaluated by spectrophotometric method . Lipid profile was determined using commercial kits , and apolipoprotein AI ( Apo-AI ) and B ( Apo-B ) levels were measured by commercial immunoturbidimetric kits . Results : In the case group , there was no significant change in the serum total cholesterol ( TC ) , triglyceride ( TG ) , low-density lipoprotein ( LDL ) , and Apo-B levels , while the serum levels of high-density lipoprotein ( HDL ) , Apo-AI , and PON activity were significantly increased ( p = 0.02 ) . In the control group , although significant increases were observed in the serum levels of TC , TG , and Apo-B ( p = 0.009 , 0.019 , and 0.001 , respectively ) , the serum PON activity was significantly decreased ( p = 0.025 ) and the serum levels of HDL , LDL , and Apo-AI were not changed . At the end of intervention period , the serum level of Apo-AI and PON activity were significantly higher in the case group . Conclusions : Zinc supplementation increased both the activity of PON and the serum level of Apo-AI in the HD patients", "Background : Obese individuals are more likely to have either lower blood concentrations or lower bioavailability of minerals and /or vitamins . However , there are limited data on the effects of nutritional supplementation on body weight ( BW ) control , energy homeostasis and lipid metabolism in obese subjects . Objective : The purpose of this study is to evaluate the effects of supplementation with multivitamin and multimineral on adiposity , energy expenditure and lipid profiles in obese Chinese women . Design : A total of 96 obese Chinese women ( body mass index ( BMI ) 28 kg m−2 ) aged 18–55 years participated in a 26-week r and omized , double-blind , placebo-controlled intervention study . Subjects were r and omized into three groups , receiving either one tablet of multivitamin and mineral supplement ( MMS ) , or calcium 162 mg ( Calcium ) or identical placebo daily during the study period . BW , BMI , waist circumference ( WC ) , fat mass ( FM ) , fat-free mass , resting energy expenditure ( REE ) , respiratory quotient ( RQ ) , blood pressure , fasting plasma glucose and serum insulin , total cholesterol ( TC ) , low- and high-density lipoprotein-cholesterol ( LDL-C and HDL-C ) and triglycerides ( TGs ) were measured at baseline and 26 weeks . Results : A total of 87 subjects completed the study . After 26 weeks , compared with the placebo group , the MMS group had significantly lower BW , BMI , FM , TC and LDL-C , significantly higher REE and HDL-C , as well as a borderline significant trend of lower RQ ( P=0.053 ) and WC ( P=0.071 ) . The calcium group also had significantly higher HDL-C and lower LDL-C levels compared with the placebo group . Conclusion : The results suggest that , in obese individuals , multivitamin and mineral supplementation could reduce BW and fatness and improve serum lipid profiles , possibly through increased energy expenditure and fat oxidation . Supplementation of calcium alone ( 162 mg per day ) only improved lipid profiles", "Glycemic control and prevention of secondary complications are the most important goals of using pharmacologic treatment of diabetes mellitus ( DM ) . The inadequate responses to oral hypoglycemic agents may be attributed to inadequate postreceptor events even when insulin levels are quite sufficient , and associated with oxidative stress induced by long-term hyperglycemia . The administration of antioxidants such as melatonin and zinc may improve tissue responses to insulin and increase the efficacy of drugs , e.g. metformin , which act through this pathway . This project was design ed to evaluate the effects of melatonin and zinc on the lipid profile and renal function in type 2 DM patients poorly controlled with metformin . A placebo-controlled , double-blind clinical trial was performed in which 46 type 2 diabetic patients were selected and allocated into three groups . These groups were treated with single daily oral doses of both 10 mg of melatonin and 50 mg of zinc acetate alone : 10 mg of melatonin and 50 mg of zinc acetate in addition to the regularly used metformin or placebo , given at bedtime for 90 days . Fasting lipid profiles and microalbuminuria ( MAU ) were measured before initiating the treatments ( zero time ) and after 30 and 90 days of treatment . Daily administration of melatonin and zinc improved the impaired lipid profile and decreased the level of MAU ; the addition of this treatment regimen in combination with metformin improved the tissue responses to this oral hypoglycemic agent . In conclusion , the combination of melatonin and zinc acetate , when used alone or in combination with metformin , improves DM-related complications such as the impaired lipid profile and MAU in type 2 DM patients", "As part of a study to determine the effect of 150 mg zinc/day on plasma lipoproteins , healthy young female ( n = 26 ; mean age 27 years ) and male ( n = 21 ; mean age 28 years ) volunteers took part in a double-blind cross-over trial lasting 12 weeks . During 6 weeks of supplementation , plasma Zn rose significantly in both groups , indicating compliance . Plasma total cholesterol remained unchanged in both males and females . However , mean LDL-cholesterol decreased from 2.38 to 2.17 mmol/l in females and there was a trend for total HDL-cholesterol to be redistributed in that HDL2 rose and HDL3 fell slightly . In parallel with these changes in females , Zn supplements reduced the ferroxidase activity of serum caeruloplasmin ( from 13.0 to 11.3 U/ml ) and the antioxidant activity of erythrocyte superoxide dismutase ( E-SOD ) ( from 4557 to 3638 U/g Hb ) and CuZn E-SOD ( from 2184 to 1672 U/g Hb ) . Plasma Cu and haematocrit were unaffected . No such changes were seen in males in either lipoproteins or these indicators of Cu status . Since the females were lighter than the males but received the same dose , a dose-response effect rather than a sex difference can not be ruled out . Overall , Zn supplements significantly decrease a major risk factor for CHD in females but reduced their Cu status", "CONTEXT The role of triglycerides in the risk of ischemic stroke remains controversial . Recently , a strong association was found between elevated levels of nonfasting triglycerides , which indicate the presence of remnant lipoproteins , and increased risk of ischemic heart disease . OBJECTIVE To test the hypothesis that increased levels of nonfasting triglycerides are associated with ischemic stroke in the general population . DESIGN , SETTING , AND PARTICIPANTS The Copenhagen City Heart Study , a prospect i ve , Danish population -based cohort study initiated in 1976 , with follow-up through July 2007 . Participants were 13,956 men and women aged 20 through 93 years . A cross-sectional study included 9637 individuals attending the 1991 - 1994 examination of the prospect i ve study . MAIN OUTCOME MEASURES Prospect i ve study : baseline levels of nonfasting triglycerides , other risk factors at baseline and at follow-up examinations , and incidence of ischemic stroke . Cross-sectional study : levels of nonfasting triglycerides , levels of remnant cholesterol , and prevalence of ischemic stroke . RESULTS Of the 13,956 participants in the prospect i ve study , 1529 developed ischemic stroke . Cumulative incidence of ischemic stroke increased with increasing levels of nonfasting triglycerides ( log-rank trend , P nonfasting triglyceride levels of 89 through 176 mg/dL had multivariate-adjusted hazard ratios ( HRs ) for ischemic stroke of 1.3 ( 95 % CI , 0.8 - 1.9 ; 351 events ) ; for 177 through 265 mg/dL , 1.6 ( 95 % CI , 1.0 - 2.5 ; 189 events ) ; for 266 through 353 mg/dL , 1.5 ( 95 % CI , 0.9 - 2.7 ; 73 events ) ; for 354 through 442 mg/dL , 2.2 ( 95 % CI , 1.1 - 4.2 ; 40 events ) ; and for 443 mg/dL or greater , 2.5 ( 95 % CI , 1.3 - 4.8 ; 41 events ) vs men with nonfasting levels less than 89 mg/dL ( HR , 1.0 ; 85 events ) ( P triglyceride levels less than 89 mg/dL ( HR , 1.0 ; 159 events ) ( P 10-year risk of ischemic stroke ranged from 2.6 % in men younger than 55 years with nonfasting triglyceride levels of less than 89 mg/dL to 16.7 % in men aged 55 years or older with levels of 443 mg/dL or greater . Corresponding values in women were 1.9 % and 12.2 % . In the cross-sectional study , men with a previous ischemic stroke vs controls had nonfasting triglyceride levels of 191 ( IQR , 131 - 259 ) mg/dL vs 148 ( IQR , 104 - 214 ) mg/dL ( P remnant cholesterol , corresponding values were 38 ( IQR , 26 - 51 ) mg/dL vs 29 ( IQR , 20 - 42 ) mg/dL in men ( P nonfasting triglyceride levels were associated with risk of ischemic stroke", "Recent studies in animals and in vitro support the hypothesis that zinc , an essential micronutrient , possesses antioxidant properties . The aims of this study were to determine whether zinc provides antioxidant protection in humans by decreasing low-density lipoprotein ( LDL ) oxidizability and to determine the effect of zinc supplementation on plasma lipid and its distribution among lipoproteins . Ten healthy male volunteers were recruited to participate in a r and omized crossover trial . Subjects were asked to consume 50 mg zinc as 220 mg zinc sulphate ( equivalent to 4 x recommended dietary intake , or RDI ) daily for 4 weeks , followed by placebo , and vice versa . Venous blood sample s were collected at 2-week intervals for the determination of plasma lipids and the in vitro oxidizability of LDL in the presence of copper ions . No changes in the oxidizability of LDL or the plasma concentrations of total cholesterol , high-density lipoprotein ( HDL ) cholesterol and its subfractions , LDL cholesterol , or triacylglycerol were observed following zinc supplementation compared to placebo . Plasma zinc concentrations were increased significantly , indicating that the lack of effect was not due to poor compliance . The antioxidant effect of zinc in relation to LDL was not demonstrated in humans at this dose , and higher doses are unlikely to be effective given the adverse interaction with copper metabolism and the potential decrease in the activity of superoxide dismutase , a free radical quenching enzyme . The findings of this study suggest that zinc provides little , if any , antioxidant protection against LDL oxidation in humans", "Zn has been shown to possess antioxidant properties in vitro and in vivo . As inadequate dietary Zn intake has been reported in these population s , Zn supplementation may protect against oxidative stress and thereby limit the progression of degenerative diseases in such population s. We conducted the present study to evaluate the long-term supplementation effects of two moderate doses of Zn on in vitro Cu-induced LDL oxidation in French men and women . Three groups of sixteen healthy subjects aged 55 - 70 years from each sex participated in this r and omized double-blind , placebo-controlled study . Each group received for six months either 0 , 15 or 30 mg supplemental Zn per d. At the beginning and at the end of the supplementation periods , dietary intakes of Zn , Cu , Fe and vitamin E were estimated using 4 d food-intake records ( including the weekend ) and the GENI program . Zn , Cu , Fe and vitamin E status were also determined . In vitro LDL oxidizability ( basal conjugated diene level , maximal conjugated diene formation and lag time ) and lipid parameters were also determined . Dietary intakes of Zn , Cu , Fe and vitamin E were adequate in this population . Zn supplementation significantly increased serum Zn levels but did not significantly modify Cu , Fe or vitamin E status . However , Zn supplementation had no effect on in vitro LDL oxidation parameters , nor were there any sex-related differences in in vitro LDL oxidizability . The present study showed that long-term Zn supplementation of healthy subjects aged 55 - 70 years had no effect on in vitro Cu-induced LDL oxidation under the study conditions", "OBJECTIVE To examine the effect of zinc sulfate supplementation on the concentrations of serum zinc and serum cholesterol in hemodialysis ( HD ) patients . SETTING Outpatient dialysis center in a large metropolitan city . DESIGN R and omized , double-blind , before-after trial . PATIENTS Twenty-eight maintenance HD patients were selected . Twenty ( 15 women and 5 men ) completed the study . Subjects were identified for inclusion in the study by the following criteria : HD treatment for a minimum of 6 months , no signs of gastrointestinal disorders , and no record of hospitalizations for reasons other than vascular access complications within the last 3 months . INTERVENTIONS Patients were given a daily supplement of 7.7 micromol zinc sulfate ( 50 mg elemental zinc ) or a cornstarch placebo capsule for 90 days . Patients completed 2-day food records , at day 0 and day 90 of the study , which included 1 dialysis day and 1 nondialysis day . MAIN OUTCOME MEASURE Fasting , predialysis serum sample s were collected on days 0 , 40 , and 90 to determine serum zinc and total cholesterol ( TCHOL ) concentrations . Dietary parameters , including zinc , protein , and energy intake , were also analyzed on days 0 and 90 . RESULTS Initial concentrations of serum zinc indicated subjects were below the normal range for serum zinc st and ards ( 12 micromol/L [ 80 microg/dL ] ) . After supplementation , subjects in the zinc-supplemented group showed significant increases in serum zinc concentrations from 0.79 microg/mL at day 0 to 0.96 microg/mL at day 90 . Serum TCHOL concentrations were initially low among subjects in the control ( 2.914 + /- 0.158 mmol/L [ 112.7 + /- 6.1 mg/dL ] ) and zinc-supplemented ( 3.155 + /- 0.354 mmol/L [ 122.0 + /- 13.7 mg/dL ] ) groups . Serum TCHOL concentrations in the control group increased slightly throughout the study period but did not reach statistical significance . A progressive increase in serum TCHOL concentration was observed in the zinc-supplemented group from the beginning ( 3.155 + /- 0.354 mmol/L [ 122.0 + /- 13.7 mg/dL ] ) to the end ( 4.445 + /- 0.478 mmol/L [ 171.9 + /- 18.5 mg/dL ] ) of the study ( r = .63 , P Mean serum high-density lipoprotein ( HDL ) cholesterol concentrations for the zinc-supplemented group were 0.959 mmol/L + /- 0.11 ( 37.1 mg/dL + /- 4.3 ) , 0.825 mmol/L + /- 0.08 ( 31.9 mg/dL + /- 3.2 ) , and 0.908 mmol/L + /- 0.10 ( 35.1 mg/dL + /- 3.9 ) from the beginning to the end of the experimental period . The mean serum HDL cholesterol concentrations for the control group were 0.760 mmol/L + /- 0.075 ( 29.4 mg/dL + /- 2.9 ) , 0.760 + /- 0.08 ( 29.4 mg/dL + /- 3.0 ) , and 0.799 mmol/L + /- 0.13 ( 30.9 mg/dL + /- 4.9 ) from the beginning to the end of the experimental period . A progressive increase in low-density lipoprotein ( LDL ) cholesterol concentration was observed for the zinc-supplemented group throughout the study . Mean LDL cholesterol concentrations for the zinc-supplemented group were 2.19 mmol/L + /- 0.39 ( 85 mg/dL + /- 15.0 ) , 3.30 mmol/L + /- 0.36 ( 127.8 mg/dL + /- 14.1 ) , and 3.53 mmol/L + /- 0.53 ( 136.7 mg/dL + /- 20.6 ) from the beginning to the end of the study period . When serum zinc concentration was correlated with serum LDL cholesterol concentration , a significant correlation was found ( r = .62 , P LDL cholesterol concentrations were found within the control group from the beginning to the end of the study . Dietary intake of zinc , cholesterol , total fat , and saturated fat remained constant and did not statistically influence serum values . Reported energy intake increased significantly in the zinc-supplemented group from 5,799 kJ/24 h ( 1,385 kcal/d ) at day 0 to 7,042 kJ/24 h ( 1,682 kcal/d ) at day 90 . CONCLUSION Zinc supplementation is an effective means of improving serum levels of zinc and cholesterol in the HD patient", "CONTEXT Elevated nonfasting triglycerides indicate the presence of remnant lipoproteins , which may promote atherosclerosis . OBJECTIVE To test the hypothesis that very high levels of nonfasting triglycerides predict myocardial infa rct ion ( MI ) , ischemic heart disease ( IHD ) , and death . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve cohort study of 7587 women and 6394 men from the general population of Copenhagen , Denmark , aged 20 to 93 years , followed up from baseline ( 1976 - 1978 ) until 2004 . MAIN OUTCOME MEASURES Hazard ratios ( HRs ) for incident MI , IHD , and total death according to baseline nonfasting triglyceride level categories of 1 to 1.99 mmol/L ( 88.5 - 176.1 mg/dL ) , 2 to 2.99 mmol/L ( 177.0 - 264.6 mg/dL ) , 3 to 3.99 mmol/L ( 265.5 - 353.0 mg/dL ) , 4 to 4.99 mmol/L ( 354.0 - 441.6 mg/dL ) , and 5 mmol/L or more ( > or = 442.5 mg/dL ) vs triglyceride levels of less than 1 mmol/L ( , levels of remnant lipoprotein cholesterol increased . During a mean follow-up of 26 years , 1793 participants ( 691 women and 1102 men ) developed MI , 3479 ( 1567 women and 1912 men ) developed IHD , and 7818 ( 3731 women and 4087 men ) died . For MI , among women , the age-adjusted HRs and multifactorially adjusted HRs ( aHRs ) for each respective category per 1-mmol/L increase in nonfasting triglyceride levels were 2.2 ( aHR , 1.7 ) , 4.4 ( aHR , 2.5 ) , 3.9 ( aHR , 2.1 ) , 5.1 ( aHR , 2.4 ) , and 16.8 ( aHR , 5.4 ) ; for both , P for trend MI , among men , the values were 1.6 ( aHR , 1.4 ) , 2.3 ( aHR , 1.6 ) , 3.6 ( aHR , 2.3 ) , 3.3 ( aHR , 1.9 ) , and 4.6 ( aHR , 2.4 ) ; for both , P for trend IHD , among men , the values were 1.3 ( aHR , 1.1 ) , 1.7 ( aHR , 1.3 ) , 2.1 ( aHR , 1.3 ) , 2.0 ( aHR , 1.2 ) , and 2.9 ( aHR , 1.5 ) ; P for trend total death , among women , the values were 1.3 ( aHR , 1.3 ) , 1.7 ( aHR , 1.6 ) , 2.2 ( aHR , 2.2 ) , 2.2 ( aHR , 1.9 ) , and 4.3 ( aHR , 3.3 ) ; for both , P for trend total death , among men , the values were 1.3 ( aHR , 1.2 ) , 1.4 ( aHR , 1.4 ) , 1.7 ( aHR , 1.5 ) , 1.8 ( aHR , 1.6 ) , and 2.0 ( aHR , 1.8 ) ; for both , P for trend this general population cohort , elevated nonfasting triglyceride levels were associated with increased risk of MI , IHD , and death in men and women", "A retinol ( 15 mg ) , riboflavin ( 200 mg ) and zinc ( 50 mg ) supplement or a placebo ( D-mannitol ) was given to 610 Chinese farmers weekly for 13.5 months . Riboflavin , retinol , beta-carotene , tocopherol and zinc status were measured in all subjects at the start and end of the intervention and in a sub sample at 2 months . Plasma vitamin C , haemoglobin and haematocrits were measured on other sub sample s at the end of the supplementation period . At the start vitamin A , zinc and riboflavin status were poor . Plasma retinol and zinc concentrations were higher in men than women but the opposite was observed with respect to beta-carotene . There was no difference between the sexes for tocopherol and riboflavin . Tocopherol : cholesterol ratios suggested vitamin E status was good and vitamin C status also appeared adequate . The supplement increased plasma retinol throughout the whole period but riboflavin status improved only over the first 2 months and then remained constant . Plasma zinc increased in both treatment and placebo groups by approximately 15 to 20 per cent in men and women . Mean concentrations of retinol and tocopherol and beta-carotene ( in women only ) increased by approximately 20 per cent in the placebo group . It is argued that seasonal factors and /or the placebo may have been responsible for the increase in retinol and beta-carotene in the placebo group . The lack of an increase in beta-carotene in the men may have been due to their higher retinol requirements . Lastly , the increase in retinol may have been responsible for the increase in tocopherol and zinc in plasma since these nutrients increased in those whose plasma retinol increased , irrespective of treatment", "CONTEXT The association of triglycerides with incident cardiovascular disease remains controversial . Although triglyceride levels are typically obtained in the fasting state , postpr and ial hypertriglyceridemia may play an important role in atherosclerosis . OBJECTIVE To determine the association of triglyceride levels ( fasting vs nonfasting ) and risk of future cardiovascular events . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve study of 26,509 initially healthy US women ( 20,118 fasting and 6391 nonfasting ) participating in the Women 's Health Study , enrolled between November 1992 and July 1995 and undergoing follow-up for a median of 11.4 years . Triglyceride levels were measured in blood sample s obtained at time of enrollment . MAIN OUTCOME MEASURE Hazard ratios for incident cardiovascular events ( nonfatal myocardial infa rct ion , nonfatal ischemic stroke , coronary revascularization , or cardiovascular death ) . RESULTS At baseline , triglyceride levels in fasting as well as nonfasting women correlated with traditional cardiac risk factors and markers of insulin resistance . During a median follow-up of 11.4 years , 1001 participants experienced an incident cardiovascular event ( including 276 nonfatal myocardial infa rct ions , 265 ischemic strokes , 628 coronary revascularizations , and 163 cardiovascular deaths ) , for an overall rate of 3.46 cardiovascular events per 1000 person-years of follow-up . After adjusting for age , blood pressure , smoking , and use of hormone therapy , both fasting and nonfasting triglyceride levels predicted cardiovascular events . Among fasting participants , further adjustment for levels of total and high-density lipoprotein cholesterol and measures of insulin resistance weakened this association ( fully adjusted hazard ratio [ 95 % confidence interval ] for increasing tertiles of triglyceride levels : 1 [ reference ] , 1.21 [ 0.96 - 1.52 ] , and 1.09 [ 0.85 - 1.41 ] [ P = .90 for trend ] ) . In contrast , nonfasting triglyceride levels maintained a strong independent relationship with cardiovascular events in fully adjusted models ( hazard ratio [ 95 % confidence interval ] for increasing tertiles of levels : 1 [ reference ] , 1.44 [ 0.90 - 2.29 ] , and 1.98 [ 1.21 - 3.25 ] [ P = .006 for trend ] ) . In secondary analyses stratified by time since participants ' last meal , triglyceride levels measured 2 to 4 hours postpr and ially had the strongest association with cardiovascular events ( fully adjusted hazard ratio [ 95 % confidence interval ] for highest vs lowest tertiles of levels , 4.48 [ 1.98 - 10.15 ] [ P initially healthy women , nonfasting triglyceride levels were associated with incident cardiovascular events , independent of traditional cardiac risk factors , levels of other lipids , and markers of insulin resistance ; by contrast , fasting triglyceride levels showed little independent relationship", "OBJECTIVE The purpose of the present study was to assess the impact of Mg + Zn , Vitamins C + E , and combination of these micronutrients on serum lipid and lipoprotein profiles in type 2 diabetic patients . MATERIAL S AND METHODS In a r and omized , double-blind , placebo controlled clinical trial , 69 type 2 diabetic patients were r and omly divided into four groups , each group receiving one of the following daily supplement for 3 months ; group M : 200 mg Mg and 30 mg Zn ( n = 16 ) , group V : 200 mg Vitamin C and 150 mg Vitamin E ( n = 18 ) , group MV : minerals plus vitamins ( n = 17 ) , group P : placebo ( n = 18 ) . Fasting blood and urine sample s were collected at the beginning and at the end of the trial . Serum triglyceride , total cholesterol , high density lipoprotein cholesterol ( HDL-c ) and low density lipoprotein cholesterol ( LDL-c ) were measured enzymatically . Apolipoproteins ( apo ) A1 and B were measured by immunoturbidimetric method . Adjustment for differences in baselines covariates and changes in variables during study were performed by analysis of covariance using general linear models . RESULTS Results indicate that after 3 months of supplementation mean serum levels of HDL-c and apo A1 increased significantly in the MV group by 24 % ( 50.4 + /-19.3 mg/dl versus 40.6 + /- 10.8 mg/dl ) and 8.8 % ( 169.8 + /- 33.8 mg/dl versus 156.1 + /- 23.9 mg/dl ) , respectively ( P Serum levels of total cholesterol , LDL-c , triglyceride , and apo B were not altered after supplementation in all four groups . CONCLUSION It is concluded that since co-supplementation of Mg , Zn , Vitamins C and E significantly increases HDL-c and apo A1 , supplementation of these micronutrients could be recommended for the type 2 diabetic patients based on their daily requirements", "The finding that high doses ( 160 mg ) of zinc lowered high-density lipoprotein-cholesterol prompted us to study the effect of low-dose zinc supplementation on lipoprotein values in sedentary and endurance-trained men . Twenty-one endurance-trained and 23 sedentary men received either placebo or 50 mg of zinc sulfate daily for eight weeks . Despite the fact that plasma zinc increased 15 % , fasting plasma high-density-lipoprotein cholesterol , total cholesterol , low-density-lipoprotein cholesterol , and triglyceride levels did not change in response to zinc ingestion . We conclude that low-dose zinc supplementation does not affect lipid or lipoprotein values in either endurance-trained or sedentary men" ]	41189bea-06ff-11f0-808a-c43d1ab1c353
Purpose of Review The current approach to diabetes in the elderly incorporates components from the comprehensive geriatric approach . The most up date d guidelines from the American Diabetes Association reflect influence from the consensus made in 2012 with the American Geriatrics Society . Notably , the framework included the evaluation for geriatric syndromes ( falls and urinary incontinence ) , functional and cognitive abilities . The goal for this review is to provide an up date d summary of treatment strategies for community-dwelling older adults . We identified the need to exp and our approach by addressing innovative approaches and scientific concepts from telemedicine , functional medicine , and geriatrics . Recent Findings Findings on cardiovascular protection with sodium-glucose co-transporter 2 inhibitors ( SGLT-2i ) and some glucagon-like peptide 1 receptor agonists ( GLP-1RA ) support their use for older patients with diabetes . However , careful consideration for agent selection must incorporate the presence of geriatric issues , such as geriatric syndromes , or functional and cognitive decline , as they could increase the risk and impact adverse reactions . Telemedicine interventions can improve communication and connection between older patients and their providers , and improve glycemic control . Functional medicine concepts can offer additional adjuvant strategies to support the therapeutic interventions and management of diabetes in the elderly . Summary A systematic review confirmed the efficacy and safety of metformin as first-line therapy of type 2 diabetes in the older adult , but multiple reports highlighted the risk for vitamin B12 deficiency . R and omized controlled trials showed the efficacy and safety of antihyperglycemic agents in the elderly , including some with longer duration and lesser risk for hypoglycemia . R and omized clinical trials showed cardiovascular protection with SGLT-2i ( empagliflozin , canagliflozin ) and GLP-1RA ( liraglutide , semaglutide ) . The most current guidelines recommend addressing for geriatric syndromes , physical and cognitive function in the elderly , in order to individualize targets and therapeutic strategies . Clinicians managing diabetes in the elderly can play a major role for the early detection and evaluation of geriatric issues in their patients . Telemedicine interventions improve glycemic control , and certain functional medicine strategies could be adjuvant interventions to reduce inflammation and stress , but more studies focused on the elderly population are needed	[ "OBJECTIVE To evaluate the efficacy and safety of lixisenatide versus placebo on glycemic control in older patients with type 2 diabetes uncontrolled on their current antidiabetic treatment . RESEARCH DESIGN AND METHODS In this phase III , double-blind , r and omized , placebo-controlled , two-arm , parallel-group , multicenter trial , patients aged ≥70 years were r and omized to receive once-daily lixisenatide 20 μg or placebo before breakfast concomitantly with their existing antidiabetic therapy ( including insulin ) for 24 weeks . Patients at risk for malnutrition or with moderate to severe cognitive impairment were excluded . The primary end point was absolute change in HbA1c from baseline to week 24 . Secondary end points included change from baseline to week 24 in 2-h postpr and ial plasma glucose ( PPG ) and body weight . RESULTS A total of 350 patients were r and omized . HbA1c decreased substantially with lixisenatide ( −0.57 % [ 6.2 mmol/mol ] ) compared with placebo ( + 0.06 % [ 0.7 mmol/mol ] ) from baseline to week 24 ( P was significantly greater with lixisenatide ( −5.12 mmol/L ) than with placebo ( −0.07 mmol/L ; P ) . A greater decrease in body weight was observed with lixisenatide ( −1.47 kg ) versus placebo ( −0.16 kg ; P ) . The safety profile of lixisenatide in this older population , including rates of nausea and vomiting , was consistent with that observed in other lixisenatide studies . Hypoglycemia was reported in 17.6 % of patients with lixisenatide versus 10.3 % with placebo . CONCLUSIONS In nonfrail older patients uncontrolled on their current antidiabetic treatment , lixisenatide was superior to placebo in HbA1c reduction and in targeting postpr and ial hyperglycemia , with no unexpected safety findings", "As life expectancy becomes longer in Japan , there has been an increase of elderly patients with type 2 diabetes who need insulin therapy but can not perform self-injection due to dementia or other conditions . Therefore , the aim of this study was to investigate the efficacy and safety of thrice-weekly insulin degludec therapy in elderly patients with poorly controlled diabetes . The subjects were 22 hospitalized elderly Japanese patients with type 2 diabetes who had difficulty with self-injection . After becoming stable on once-daily insulin degludec treatment , they were assigned to continue once-daily injection ( OD group ) or were switched to thrice-weekly injection ( TW group ) for one week . In the TW group , insulin degludec ( IDeg ) was injected at twice the OD dose before lunch on Monday , Wednesday , and Friday . Glycemic control was assessed by continuous glucose monitoring ( CGM ) over 7 days . The mean 7-day glucose level ( 131±25 mg/dL with OD vs. 152±30 mg/dL with TW , p=0.11 ) and the mean 7-day st and ard deviation ( 32±10 mg/dL with OD vs. 36±14 mg/dL with TW , p=0.45 ) did not differ significantly between the two groups . The percent duration of glucose 200 mg/dL ( 7.2±12.1 % with OD vs. 15.6±18.0 % with TW , p=0.22 ) over 7 days also showed no significant differences between the two groups . In conclusion , thrice-weekly IDeg provided by a visiting nurse could be a practical option for elderly diabetic patients who have difficulty performing self-injection of insulin", "BACKGROUND The cardiovascular effects of adding once‐weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown . METHODS We r and omly assigned patients with type 2 diabetes , with or without previous cardiovascular disease , to receive subcutaneous injections of extended‐release exenatide at a dose of 2 mg or matching placebo once weekly . The primary composite outcome was the first occurrence of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . The co primary hypotheses were that exenatide , administered once weekly , would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy . RESULTS In all , 14,752 patients ( of whom 10,782 [ 73.1 % ] had previous cardiovascular disease ) were followed for a median of 3.2 years ( interquartile range , 2.2 to 4.4 ) . A primary composite outcome event occurred in 839 of 7356 patients ( 11.4 % ; 3.7 events per 100 person‐years ) in the exenatide group and in 905 of 7396 patients ( 12.2 % ; 4.0 events per 100 person‐years ) in the placebo group ( hazard ratio , 0.91 ; 95 % confidence interval [ CI ] , 0.83 to 1.00 ) , with the intention‐to‐treat analysis indicating that exenatide , administered once weekly , was noninferior to placebo with respect to safety ( P to efficacy ( P=0.06 for superiority ) . The rates of death from cardiovascular causes , fatal or nonfatal myocardial infa rct ion , fatal or nonfatal stroke , hospitalization for heart failure , and hospitalization for acute coronary syndrome , and the incidence of acute pancreatitis , pancreatic cancer , medullary thyroid carcinoma , and serious adverse events did not differ significantly between the two groups . CONCLUSIONS Among patients with type 2 diabetes with or without previous cardiovascular disease , the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo . ( Funded by Amylin Pharmaceuticals ; EXSCEL Clinical Trials.gov number , NCT01144338 .", "Background Mobile health apps for diabetes self-management have different functions . However , the efficacy and safety of each function are not well studied , and no classification is available for these functions . Objective The aims of this study were to ( 1 ) develop and vali date a taxonomy of apps for diabetes self-management , ( 2 ) investigate the glycemic efficacy of mobile app-based interventions among adults with diabetes in a systematic review of r and omized controlled trials ( RCTs ) , and ( 3 ) explore the contribution of different function to the effectiveness of entire app-based interventions using the taxonomy . Methods We developed a 3-axis taxonomy with columns of clinical modules , rows of functional modules and cells of functions with risk assessment s. This taxonomy was vali date d by review ing and classifying commercially available diabetes apps . We search ed MEDLINE , EMBASE , the Cochrane Central Register of Controlled Trials , the Chinese Biomedical Literature Data base , and Clinical Trials.gov from January 2007 to May 2016 . We included RCTs of adult out patients with diabetes that compared using mobile app-based interventions with usual care alone . The mean differences ( MDs ) in hemoglobin A1c ( HbA1c ) concentrations and risk ratios of adverse events were pooled using a r and om-effects meta- analysis . After taxonomic classification , we performed exploratory subgroup analyses of the presence or absence of each module across the included app-based interventions . Results Across 12 included trials involving 974 participants , using app-based interventions was associated with a clinical ly significant reduction of HbA1c ( MD 0.48 % , 95 % CI 0.19%-0.78 % ) without excess adverse events . Larger HbA1c reductions were noted among patients with type 2 diabetes than those with type 1 diabetes ( MD 0.67 % , 95 % CI 0.30%-1.03 % vs MD 0.37 % , 95 % CI –0.12%-0.86 % ) . Having a complication prevention module in app-based interventions was associated with a greater HbA1c reduction ( with complication prevention : MD 1.31 % , 95 % CI 0.66%-1.96 % vs without : MD 0.38 % , 95 % CI 0.09%-0.67 % ; intersubgroup P=.01 ) , as was having a structured display ( with structured display : MD 0.69 % , 95 % CI 0.32%-1.06 % vs without : MD 0.69 % , 95 % CI –0.18%-0.53 % ; intersubgroup P=.03 ) . However , having a clinical decision-making function was not associated with a larger HbA1c reduction ( with clinical decision making : MD 0.19 % , 95 % CI –0.24%-0.63 % vs without : MD 0.61 % , 95 % CI 0.27%-0.95 % ; intersubgroup P=.14 ) . Conclusions The use of mobile app-based interventions yields a clinical ly significant HbA1c reduction among adult out patients with diabetes , especially among those with type 2 diabetes . Our study suggests that the clinical decision-making function needs further improvement and evaluation before being added to apps", "Background : Canagliflozin is a sodium glucose cotransporter 2 inhibitor that reduces the risk of cardiovascular events . We report the effects on heart failure ( HF ) and cardiovascular death overall , in those with and without a baseline history of HF , and in other participant subgroups . Methods : The CANVAS Program ( Canagliflozin Cardiovascular Assessment Study ) enrolled 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk . Participants were r and omly assigned to canagliflozin or placebo and followed for a mean of 188 weeks . The primary end point for these analyses was adjudicated cardiovascular death or hospitalized HF . Results : Participants with a history of HF at baseline ( 14.4 % ) were more frequently women , white , and hypertensive and had a history of prior cardiovascular disease ( all P ) . Greater proportions of these patients were using therapies such as blockers of the renin angiotensin aldosterone system , diuretics , and & bgr;-blockers at baseline ( all P Overall , cardiovascular death or hospitalized HF was reduced in those treated with canagliflozin compared with placebo ( 16.3 versus 20.8 per 1000 patient-years ; hazard ratio [ HR ] , 0.78 ; 95 % confidence interval [ CI ] , 0.67–0.91 ) , as was fatal or hospitalized HF ( HR , 0.70 ; 95 % CI , 0.55–0.89 ) and hospitalized HF alone ( HR , 0.67 ; 95 % CI , 0.52–0.87 ) . The benefit on cardiovascular death or hospitalized HF may be greater in patients with a prior history of HF ( HR , 0.61 ; 95 % CI , 0.46–0.80 ) compared with those without HF at baseline ( HR , 0.87 ; 95 % CI , 0.72–1.06 ; P interaction = 0.021 ) . The effects of canagliflozin compared with placebo on other cardiovascular outcomes and key safety outcomes were similar in participants with and without HF at baseline ( all interaction P values > 0.130 ) , except for a possibly reduced absolute rate of events attributable to osmotic diuresis among those with a prior history of HF ( P=0.03 ) . Conclusions : In patients with type 2 diabetes mellitus and an elevated risk of cardiovascular disease , canagliflozin reduced the risk of cardiovascular death or hospitalized HF across a broad range of different patient subgroups . Benefits may be greater in those with a history of HF at baseline . Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifiers : NCT01032629 and NCT01989754", "ABSTRACT Review of : Neal B , Perkovic V , Mahaffey K , et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes . N Engl J Med . 2017;377:644–657 . The report combines the data from two trials , CANVAS and CANVAS-Renal , which were design ed to evaluate the safety and effect of canagliflozin , an SGLT-2 inhibitor , on the appearance of cardiovascular and renal events in patients with type 2 diabetes . Enrollees were patients with type 2 diabetes of at least 30 years of age , with a glycated hemoglobin of > or equal to 7.0 % and 30 ml/min . Patients were r and omized to canagliflozin at doses of either 100 mg or 300 mg or matching placebo in CANVAS , and to canagliflozin 100 mg with a possible increase to 300 mg , or placebo , in CANVAS-Renal . Physicians were instructed to continue appropriate diabetic management and other therapies in accordance with the best practice s in their community . There was a significant 14 % reduction in the combined endpoint of cardiovascular events of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke in the canagliflozin treated patients . There was also a pattern of improvement in markers of renal disease , including the change in the level and nature of albuminuria , a 40 % decrease in the glomerular filtration rate , the need for renal replacement therapy , or death from renal causes . This study exp and s the scope of SGLT-2 inhibitor therapy to prevent cardiovascular disease in diabetic patients beyond those with preexisting cardiovascular disease studied in the previous empagliflozin study , raising the question as to whether SGLT-2 inhibitor therapy should be considered appropriate for most , if not all , type 2 diabetes patients , not only to control hyperglycemia but also to reduce cardiovascular and renal events", "IMPORTANCE Optimal strategies for glucose control in very old adults with diabetes and stable ischemic heart disease ( SIHD ) are unclear . OBJECTIVE To compare the effects of insulin provision ( IP ) therapy versus insulin sensitizing ( IS ) therapy for glycemic control in older ( ≥75years ) and younger ( DESIGN , SETTING , AND PARTICIPANTS Adults enrolled in the Bypass Angioplasty Revascularization Investigation 2 Diabetes ( BARI 2D ) were studied . The BARI 2D study population ( all with type II DM and SIHD ) was r and omized twice : ( 1 ) between revascularization plus intensive medical therapy versus intensive medical therapy alone , and ( 2 ) between IP versus IS therapies . The primary endpoint was all-cause-mortality over five-year follow-up . In this sub study outcomes related to IP vs. IS are assessed in relation to age . Adults aged ≥75years who received IP versus IS are compared to those who received IP versus IS . Multivariate Cox regression analysis was used to evaluate the effects of IP vs. IS on outcomes in the two age groups . RESULTS 2368 subjects with SIHD and DM were enrolled in BARI 2D ; 182 ( 8 % ) were ≥75years . Compared to younger subjects , the older cohort had lower BMI , higher diuretic use , worse kidney function , and increased history of heart failure . Within the older cohort , the IP and IS subgroups were similar in respect to baseline cardiovascular risk factors , medications , and coronary artery disease severity . During follow-up , the older subjects receiving IP therapy had higher cardiovascular mortality compared to those receiving IS therapy ( 16 % vs. 11 % , p=0.040 ) . Using Cox proportional hazards analysis , the older IP subjects were at increased risk for all-cause-mortality ( hazard ratio 1.89 , CI 1.1 - 3.2 , p=0.020 ) . No mortality difference between IP and IS was observed in those adults with diabetes and SIHD aged ≥75years , IP therapy may be associated with increased mortality compared to IS therapy . Additional studies are needed to further refine optimal treatment strategies for diabetes and SIHD in old age", "Background Previous studies have shown that individuals with diabetes exhibit accelerated cognitive decline . However , method ological limitations have limited the quality of this evidence . Heterogeneity in study design , cognitive test administration , and methods of analysis of cognitive data have made it difficult to synthesize and translate findings to practice . We analyzed longitudinal data from the Ginkgo Evaluation of Memory Study to test our hypothesis that older adults with diabetes have greater test-specific and domain-specific cognitive declines compared to older adults without diabetes . Methods Tests of memory , visuo-spatial construction , language , psychomotor speed , and executive function were administered . Test scores were st and ardized to z-scores and averaged to yield domain scores . Linear r and om effects models were used to compare baseline differences and changes over time in test and domain scores among individuals with and without diabetes . Results Among the 3,069 adults , aged 72 - 96 years , 9.3 % reported diabetes . Over a median follow-up of 6.1 years , participants with diabetes exhibited greater baseline differences in a test of executive function ( trail making test , Part B ) and greater declines in a test of language ( phonemic verbal fluency ) . For the composite cognitive domain scores , participants with diabetes exhibited lower baseline executive function and global cognition domain scores , but no significant differences in the rate of decline . Conclusions Identifying cognitive domains most affected by diabetes can lead to targeted risk modification , possibly in the form of lifestyle interventions such as diet and physical activity , which we know to be beneficial for improving vascular risk factors , such as diabetes , and therefore may reduce the risk of executive dysfunction and possible dementia", "BACKGROUND This study was performed to determine the effectiveness of the Smart Care service on glucose control based on telemedicine and telemonitoring compared with conventional treatment in patients with type 2 diabetes . MATERIAL S AND METHODS This 24-week prospect i ve multi-center r and omized controlled trial involved 338 adult patients with type 2 diabetes at four university hospitals in South Korea . The patients were r and omly assigned to a control group ( group A , n = 113 ) , a telemonitoring group ( group B , n = 113 ) , or a telemedicine group ( group C , n = 112 ) . Patients in the telemonitoring group visited the outpatient clinic regularly , accompanied by an additional telemonitoring service that included remote glucose monitoring with automated patient decision support by text . Remote glucose monitoring was identical in the telemedicine group , but assessment by outpatient visits was replaced by video conferencing with an endocrinologist . RESULTS The adjusted net reductions in HbA1c concentration after 24 weeks were similar in the conventional , telemonitoring , and telemedicine groups ( -0.66 % ± 1.03 % vs. -0.66 % ± 1.09 % vs. -0.81 % ± 1.05 % ; p > 0.05 for each pairwise comparison ) . Fasting glucose concentrations were lower in the telemonitoring and telemedicine groups than in the conventional group . Rates of hypoglycemia were lower in the telemedicine group than in the other two groups , and compliance with medication was better in the telemonitoring and telemedicine than in the conventional group . No serious adverse events were associated with telemedicine . CONCLUSIONS Telehealthcare was as effective as conventional care at improving glycemia in patients with type 2 diabetes without serious adverse effects ", "More than 25 % of the U.S. population aged ≥65 years has diabetes ( 1 ) , and the aging of the overall population is a significant driver of the diabetes epidemic . Although the burden of diabetes is often described in terms of its impact on working-age adults , diabetes in older adults is linked to higher mortality , reduced functional status , and increased risk of institutionalization ( 2 ) . Older adults with diabetes are at substantial risk for both acute and chronic microvascular and cardiovascular complications of the disease . Despite having the highest prevalence of diabetes of any age-group , older persons and /or those with multiple comorbidities have often been excluded from r and omized controlled trials of treatments— and treatment targets — for diabetes and its associated conditions . Heterogeneity of health status of older adults ( even within an age range ) and the dearth of evidence from clinical trials present challenges to determining st and ard intervention strategies that fit all older adults . To address these issues , the American Diabetes Association ( ADA ) convened a Consensus Development Conference on Diabetes and Older Adults ( defined as those aged ≥65 years ) in February 2012 . Following a series of scientific presentations by experts in the field , the writing group independently developed this consensus report to address the following questions : 1 . What is the epidemiology and pathogenesis of diabetes in older adults ? 2 . What is the evidence for preventing and treating diabetes and its common comorbidities in older adults ? 3 . What current guidelines exist for treating diabetes in older adults ? 4 . What issues need to be considered in individualizing treatment recommendations for older adults ? 5 . What are consensus recommendations for treating older adults with or at risk for diabetes ? 6 . How can gaps in the evidence best be filled ? According to the most recent surveillance data , the prevalence of diabetes among U.S. adults aged ≥65 years varies from 22 to 33 % , depending on the diagnostic criteria", "OBJECTIVE Limited data exist regarding safety and efficacy of antihyperglycemic drugs in older patients with type 2 diabetes . The Trial Evaluating Cardiovascular Outcomes with Sitagliptin ( TECOS ) was a r and omized , double-blind , placebo-controlled trial assessing the impact of sitagliptin on a primary composite outcome of cardiovascular death , nonfatal stroke , nonfatal myocardial infa rct ion , or unstable angina hospitalizations in patients with type 2 diabetes ( HbA1c ≥6.5 % [ 48 mmol/mol ] and ≤8.0 % [ 64 mmol/mol ] ) and cardiovascular disease . We analyzed baseline characteristics and clinical outcomes for TECOS participants aged ≥75 years . RESEARCH DESIGN AND METHODS Clinical and safety event summaries are presented for older versus younger participants and for the treatment groups within the older cohort . RESULTS Of 14,351 participants with age recorded , 2,004 ( 14 % ) were ≥75 years old ( mean age 78.3 years [ SD 3.1 ] ) , with 68 % men and type 2 diabetes duration median 12.0 years ( IQR 7 , 21 ) . During 2.9 years median follow-up , older participants had higher rates of the primary outcome ( 6.46 vs. 3.67 events per 100 person-years ; hazard ratio 1.72 [ 95 % CI 1.52–1.94 ] ) , death ( 2.52 [ 2.20–2.89 ] ) , severe hypoglycemia ( 1.53 [ 1.15–2.03 ] ) , and fractures ( 1.84 [ 1.44–2.35 ] ) . In the older cohort , sitagliptin did not significantly impact the primary composite ( 1.10 [ 0.89–1.36 ] ) , death ( 1.05 [ 0.83–1.32 ] ) , heart failure hospitalization ( 0.99 [ 0.65–1.49 ] ) , severe hypoglycemia ( 1.03 [ 0.62–1.71 ] ) , rates of acute pancreatitis and pancreatic cancer , or serious adverse events . CONCLUSIONS Among older patients with well-controlled type 2 diabetes and cardiovascular disease , sitagliptin had neutral effects on cardiovascular risk and raised no significant safety concerns", "Aims To investigate the efficacy and tolerability of empagliflozin added to basal insulin‐treated type 2 diabetes . Methods Patients inadequately controlled [ glycated haemoglobin ( HbA1c ) > 7 to ≤10 % ( > 53 to ≤86 mmol/mol ) ] on basal insulin ( glargine , detemir , NPH ) were r and omized to empagliflozin 10 mg ( n = 169 ) , empagliflozin 25 mg ( n = 155 ) or placebo ( n = 170 ) for 78 weeks . The baseline characteristics were balanced among the groups [ mean HbA1c 8.2 % ( 67 mmol/mol ) , BMI 32.2 kg/m2 ] . The basal insulin dose was to remain constant for 18 weeks , then could be adjusted at investigator 's discretion . The primary endpoint was change from baseline in HbA1c at week 18 . Key secondary endpoints were changes from baseline in HbA1c and insulin dose at week 78 . Results At week 18 , the adjusted mean ± st and ard error changes from baseline in HbA1c were 0.0 ± 0.1 % ( −0.1 ± 0.8 mmol/mol ) for placebo , compared with −0.6 ± 0.1 % ( −6.2 ± 0.8 mmol/mol ) and −0.7 ± 0.1 % ( −7.8 ± 0.8 mmol/mol ) for empagliflozin 10 and 25 mg , respectively ( both p , empagliflozin 10 and 25 mg significantly reduced HbA1c , insulin dose and weight vs placebo ( all p 0.01 ) , and empagliflozin 10 mg significantly reduced systolic blood pressure vs placebo ( p = 0.004 ) . Similar percentages of patients had confirmed hypoglycaemia in all groups ( 35–36 % ) . Events consistent with urinary tract infection were reported in 9 , 15 and 12 % of patients on placebo , empagliflozin 10 and 25 mg , and events consistent with genital infection were reported in 2 , 8 and 5 % , respectively . Conclusions Empagliflozin for 78 weeks added to basal insulin improved glycaemic control and reduced weight with a similar risk of hypoglycaemia to placebo", "OBJECTIVE To examine the safety and cardiovascular ( CV ) effects of saxagliptin in the predefined elderly ( ≥65 years ) and very elderly ( ≥75 years ) sub population s of the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus – Thrombolysis in Myocardial Infa rct ion 53 ( SAVOR-TIMI 53 ) trial . RESEARCH DESIGN AND METHODS Individuals ≥40 years ( n = 16,492 ; elderly , n = 8,561 ; very elderly , n = 2,330 ) with HbA1c ≥6.5 % ( 47.5 mmol/mol ) and ≤12.0 % ( 107.7 mmol/mol ) were r and omized ( 1:1 ) to saxagliptin ( 5 or 2.5 mg daily ) or placebo in a double-blind trial for a median follow-up of 2.1 years . RESULTS The hazard ratio ( HR ) for the comparison of saxagliptin versus placebo for the primary end point ( composite of CV mortality , myocardial infa rct ion , or ischemic stroke ) was 0.92 for elderly patients vs. 1.15 for patients The HRs for the secondary composite end points in the entire cohort , elderly cohort , and very elderly cohort were similar . Although saxagliptin increased the risk of hospitalization for heart failure in the overall saxagliptin population , there was no age-based treatment interaction ( P = 0.76 for elderly patients vs. those the mean change from baseline HbA1c at 2 years was −0.69 % , −0.64 % , −0.66 % , and −0.66 % for those ≥65 , respectively . The incidence of overall adverse events ( AEs ) and serious AEs was similar between saxagliptin and placebo in all cohorts ; however , hypoglycemic events were higher for saxagliptin versus placebo regardless of age . CONCLUSIONS The SAVOR-TIMI 53 trial supports the overall CV safety of saxagliptin in a robust number of elderly and very elderly participants , although the risk of heart failure hospitalization was increased irrespective of age category . AEs and serious AEs as well as glycemic efficacy of saxagliptin in elderly patients are similar to those found in younger patients", "Background Preventing or slowing the progression of prediabetes to diabetes is a major therapeutic issue . Objectives Our aim was to evaluate the effects of 4-month treatment with a dietary supplement containing cinnamon , chromium and carnosine in moderately obese or overweight pre-diabetic subjects , the primary outcome being change in fasting plasma glucose ( FPG ) level . Other parameters of plasma glucose homeostasis , lipid profile , adiposity and inflammatory markers were also assessed . Methods In a r and omized , double-blind , placebo-controlled study , 62 subjects with a FPG level ranging from 5.55 to 7 mmol/L and a body mass index ≥25 kg/m2 , unwilling to change their dietary and physical activity habits , were allocated to receive a 4-month treatment with either 1.2 g/day of the dietary supplement or placebo . Patients were followed up until 6 months post-r and omization . Results Four-month treatment with the dietary supplement decreased FPG compared to placebo ( -0.24±0.50 vs + 0.12±0.59 mmol/L , respectively , p = 0.02 ) , without detectable significant changes in HbA1c . Insulin sensitivity markers , plasma insulin , plasma lipids and inflammatory markers did not differ between the treatment groups . Although there were no significant differences in changes in body weight and energy or macronutrient intakes between the two groups , fat-free mass ( % ) increased with the dietary supplement compared to placebo ( p = 0.02 ) . Subjects with a higher FPG level and a milder inflammatory state at baseline benefited most from the dietary supplement . Conclusions Four-month treatment with a dietary supplement containing cinnamon , chromium and carnosine decreased FPG and increased fat-free mass in overweight or obese pre-diabetic subjects . These beneficial effects might open up new avenues in the prevention of diabetes . Trial Registration Clinical Trials.gov", "Objectives To compare the efficacy and safety of canagliflozin , a sodium glucose co‐transporter 2 inhibitor developed to treat type 2 diabetes mellitus ( T2DM ) , in individuals younger than 75 and those aged 75 and older . Design R and omized Phase 3 studies . Setting International study centers . Participants Adults with T2DM . Measurements Changes from baseline in glycosylated hemoglobin ( HbA1c ) , fasting plasma glucose ( FPG ) , blood pressure ( BP ) , and body weight were measured . Efficacy was evaluated using pooled data from six r and omized , double‐blind , placebo‐controlled studies ( N = 4,158 ; n = 3,975 aged ) . Safety was assessed based on adverse event ( AE ) reports from eight r and omized , double‐blind , placebo‐ and active‐controlled studies ( N = 9,439 ; n = 8,949 aged = 490 aged ≥75 ) . Results Canagliflozin 100 and 300 mg were associated with placebo‐subtracted mean reductions in HbA1c in participants younger than 75 ( −0.69 % and −0.85 % , respectively ) and aged 75 and older ( −0.65 % and −0.55 % , respectively ) . Dose‐related reductions in FPG , body weight , and BP were seen with canagliflozin 100 and 300 mg in participants in both age groups . Overall AE incidence was 67.1 % with canagliflozin 100 mg , 68.6 % with canagliflozin 300 mg , and 65.9 % with non‐canagliflozin ( pooled group of comparators in all studies ) in participants younger than 75 , and 72.4 % , 79.1 % , and 72.3 % , respectively , in those aged 75 and older , with a similar safety profile in both groups . The incidence of volume depletion – related AEs was 2.2 % , 3.1 % , and 1.4 % in participants younger than 75 with canagliflozin 100 and 300 mg and non‐canagliflozin , respectively , and 4.9 % , 8.7 % , and 2.6 % , respectively , in those aged 75 and older . Conclusion Canagliflozin improved glycemic control , body weight , and BP in participants aged 75 and older . The overall incidence of AEs was high across treatment groups in participants aged 75 and older and higher than in those younger than 75 . The safety profile of canagliflozin was generally similar in both age groups , with a higher incidence of AEs related to volume depletion observed with canagliflozin in participants aged 75 and older than in those younger than 75 . These findings support canagliflozin , starting with the 100‐mg dose , as an effective therapeutic option for older adults with T2DM", "OBJECTIVE To analyze the relationships between cardiovascular complications and geriatric scale scores in French elderly ( ≥70 years of age ) type 2 diabetic patients at inclusion in the GERODIAB cohort . RESEARCH DESIGN AND METHODS GERODIAB is the first French multicenter , prospect i ve , observational survey design ed to analyze the influence of glycemic control on morbidity/mortality in type 2 diabetic patients aged ≥70 years during a 5-year follow-up period . This study analyzed the relationships between classical macroangiopathic complications and geriatric scale scores in 987 patients at baseline , using bivariate and multivariate analyses . RESULTS Cardiac ischemia ( 31.2 % ) was significantly associated with impaired activities of daily living ( ADL ) scores ( P with impaired Mini Mental State Examination ( MMSE ) , instrumental ADL ( IADL ) ( P and ADL scores ( P impaired IADL and ADL scores ( P were duration of diabetes , IADL score , hypertension , and sex ( 62.8 % concordance ; P with impaired MMSE , Mini Nutritional Assessment , ADL , and IADL scores ( P sex , hypertension , and ADL were included in the logistic model successively ( 65.6 % concordance ; P , impaired geriatric scale scores were found to be associated with classical macrovascular complications , notably using multivariate analyses . This suggests the benefits of thorough screening and management of cognitive and functional decline in elderly type 2 diabetic patients", "Background Diabetes , a highly prevalent , chronic disease , is associated with increasing frailty and functional decline in older people , with concomitant personal , social , and public health implication s. We describe the rationale and methods of the multi-modal intervention in diabetes in frailty ( MID-Frail ) study . Methods / Design The MID-Frail study is an open , r and omised , multicentre study , with r and om allocation by clusters ( each trial site ) to a usual care group or an intervention group . A total of 1,718 subjects will be r and omised with each site enrolling on average 14 or 15 subjects . The primary objective of the study is to evaluate , in comparison with usual clinical practice , the effectiveness of a multi-modal intervention ( specific clinical targets , education , diet , and resistance training exercise ) in frail and pre-frail subjects aged ≥70 years with type 2 diabetes in terms of the difference in function 2 years post-r and omisation . Difference in function will be measured by changes in a summary ordinal score on the short physical performance battery ( SPPB ) of at least one point . Secondary outcomes include daily activities , economic evaluation , and quality of life . Discussion The MID-Frail study will provide evidence on the clinical , functional , social , and economic impact of a multi-modal approach in frail and pre-frail older people with type 2 diabetes . Trial registration Clinical Trials.gov : NCT01654341", "Introduction Low-calorie sweetener use for weight control has come under increasing scrutiny as obesity , especially abdominal obesity , remain entrenched despite substantial low-calorie sweetener use . We evaluated whether chronic low-calorie sweetener use is a risk factor for abdominal obesity . Participants and Methods We used 8268 anthropometric measurements and 3096 food diary records with detailed information on low-calorie sweetener consumption in all food products , from 1454 participants ( 741 men , 713 women ) in the Baltimore Longitudinal Study of Aging collected from 1984 to 2012 with median follow-up of 10 years ( range : 0–28 years ) . At baseline , 785 were low-calorie sweetener non-users ( 51.7 % men ) and 669 participants were low-calorie sweetener users ( 50.1 % men ) . Time-varying low-calorie sweetener use was operationalized as the proportion of visits since baseline at which low-calorie sweetener use was reported . We used marginal structural models to determine the association between baseline and time-varying low-calorie sweetener use with longitudinal outcomes —body mass index , waist circumference , obesity and abdominal obesity — with outcome status assessed at the visit following low-calorie sweetener ascertainment to minimize the potential for reverse causality . All models were adjusted for year of visit , age , sex , age by sex interaction , race , current smoking status , dietary intake ( caffeine , fructose , protein , carbohydrate , and fat ) , physical activity , diabetes status , and Dietary Approaches to Stop Hypertension score as confounders . Results With median follow-up of 10 years , low-calorie sweetener users had 0.80 kg/m2 higher body mass index ( 95 % confidence interval [ CI ] , 0.17–1.44 ) , 2.6 cm larger waist circumference ( 95 % CI , 0.71–4.39 ) , 36.7 % higher prevalence ( prevalence ratio = 1.37 ; 95 % CI , 1.10–1.69 ) and 53 % higher incidence ( hazard ratio = 1.53 ; 95 % CI 1.10–2.12 ) of abdominal obesity than low-calorie sweetener non-users . Conclusions Low-calorie sweetener use is independently associated with heavier relative weight , a larger waist , and a higher prevalence and incidence of abdominal obesity suggesting that low-calorie sweetener use may not be an effective means of weight control", "Background and Aims Few studies have evaluated long-term durability of glycemic control in older patients . The aim of this study was to compare durability of glycemic control of twice-daily insulin lispro mix 75/25 ( LM75/25 ; 75 % insulin lispro protamine suspension , 25 % insulin lispro ) and once-daily insulin glargine ( GL ) added to oral antihyperglycemic medications in older patients ( ≥65 years of age ) . Methods Patients were participants in the maintenance phase of the DURABLE trial . During the initiation phase , patients with type 2 diabetes were r and omized to LM75/25 or GL . After 6 months , patients with hemoglobin A1c ( HbA1c ) ≤7.0 % advanced to the 24-month maintenance phase . The primary objective was between-group comparison of duration of maintaining the HbA1c goal in older patients ( ≥65 years of age ) . A similar analysis was conducted for older patients achieving HbA1c ≤6.5 % in the initiation phase . Results Median time of maintaining HbA1c goal was longer in LM75/25 versus GL ( 19.6 versus 15.4 months , p = 0.007 ) and more LM75/25 patients maintained goal versus GL ( 49.2 versus 30.4 % ; p = 0.003 ) . HbA1c reduction from baseline was greater in LM75/25 versus GL ( −1.56 ± 0.10 versus −1.24 ± 0.11 % ; p = 0.003 ) . Post-meal glucose was significantly lower in LM75/25 versus GL ( 158.86 ± 3.42 versus 171.67 ± 4.51 mg/dL ; p = 0.017 ) . No differences were observed in overall and severe hypoglycemia . LM75/25 patients had higher daily insulin doses ( 0.41 ± 0.02 versus 0.32 ± 0.02 units/kg/day ; p weight gain ( 5.47 ± 0.49 versus 3.10 ± 0.53 kg ; p = 0.001 ) . Similar results were generally obtained in older patients with HbA1c ≤6.5 % . Conclusions In our evaluation of older patients from a larger trial , LM75/25 appeared to provide longer durability of glycemic control , as well as a greater number of patients maintaining HbA1c goal versus GL", "Aims To determine the effects of empagliflozin on blood pressure ( BP ) and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes mellitus ( T2DM ) . Methods We conducted a post hoc analysis of data from a phase III trial in patients with T2DM and hypertension receiving 12 weeks ' empagliflozin and four phase III trials in patients with T2DM receiving 24 weeks ' empagliflozin ( cohort 1 , n = 823 ; cohort 2 , n = 2477 ) . BP was measured using 24‐h BP monitoring ( cohort 1 ) or seated office measurements ( cohort 2 ) . Results Empagliflozin reduced systolic BP ( SBP ) and diastolic BP in both cohorts ( p vs placebo ) , without increasing heart rate . Empagliflozin reduced pulse pressure ( PP ; adjusted mean difference vs placebo cohort 1 : −2.3 mmHg ; cohort 2 : −2.3 mmHg ) , mean arterial pressure ( MAP ; cohort 1 , −2.3 mmHg ; cohort 2 , −2.1 mmHg ) and double product ( cohort 1 , −385 mmHg × bpm ; cohort 2 , −369 mmHg × bpm ) all p vs placebo . There was a trend towards a reduction in the ambulatory arterial stiffness index ( AASI ) with empagliflozin in cohort 1 ( p = 0.059 vs placebo ) . AASI was not measured in cohort 2 . Subgroup analyses showed that there were greater reductions in PP with increasing baseline SBP in cohort 1 ( p = 0.092 ) . In cohort 2 , greater reductions in MAP were achieved in patients with higher baseline SBP ( p = 0.027 ) and greater reductions in PP were observed in older patients ( p = 0.011 ) . Conclusions Empagliflozin reduced BP and had favourable effects on markers of arterial stiffness and vascular resistance", "BACKGROUND A substantial proportion of patients with type 2 diabetes are elderly ( ≥65 years ) but this group has been largely excluded from clinical studies of glucose-lowering drugs . We aim ed to assess the effectiveness of linagliptin , a dipeptidyl peptidase-4 inhibitor , in elderly patients with type 2 diabetes . METHODS In this r and omised , double-blind , parallel-group , multinational phase 3 study , patients aged 70 years or older with type 2 diabetes , glycated haemoglobin A1c ( HbA1c ) of 7·0 % or more , receiving metformin , sulfonylureas , or basal insulin , or combinations of these drugs , were r and omised ( by computer-generated r and omisation sequence , concealed with a voice-response system , stratified by HbA1c level [ once-daily oral treatment with linagliptin 5 mg or matching placebo for 24 weeks . Investigators and participants were masked to assignment throughout the study . The primary endpoint was change in HbA1c from baseline to week 24 . This trial is registered with Clinical Trials.gov , number NCT01084005 . FINDINGS 241 community-living out patients were r and omised ( 162 linagliptin , 79 placebo ) . Mean age was 74·9 years ( SD 4·3 ) . Mean HbA1c was 7·8 % ( SD 0·8 ) . At week 24 , placebo-adjusted mean change in HbA1c with linagliptin was -0·64 % ( 95 % CI -0·81 to -0·48 , p tolerability were much the same between the linagliptin and placebo groups ; 75·9 % of patients in both groups had an adverse event ( linagliptin n=123 , placebo n=60 ) . No deaths occurred . Serious adverse events occurred in 8·6 % ( 14 ) of patients in the linagliptin group and 6·3 % ( five ) patients in the placebo group ; none were deemed related to study drug . Hypoglycaemia was the most common adverse event in both groups , but did not differ between groups ( 24·1 % [ 39 ] in the linagliptin group , 16·5 % [ 13 ] in the placebo group ; odds ratio 1·58 , 95 % CI 0·78 - 3·78 , p=0·2083 ) . INTERPRETATION In elderly patients with type 2 diabetes linagliptin was efficacious in lowering glucose with a safety profile similar to placebo . These findings could inform treatment decisions for achieving individualised glycaemic goals with minimal risk in this important population of patients . FUNDING Boehringer Ingelheim", "Objective The aim of this study was to evaluate the safety and tolerability of sitagliptin 100 mg/day in elderly patients with type 2 diabetes . Design A post hoc pooled analysis of 25 r and omized , double-blind , parallel group clinical studies with results available as of 1 December 2011 . Setting Multicenter , international clinical trials . Subjects Patients with type 2 diabetes aged 65 years or older . Interventions Patients were r and omized to sitagliptin 100 mg/day ( n = 1,261 ) or a comparator ( n = 1,185 ) for 12 weeks to 2 years . Main Outcome Measures In each study , investigators reported serious and non-serious adverse events that occurred during the study , and serious adverse events occurring within 14 days following the last dose of study drug . This analysis used patient-level data from each study to assess the exposure-adjusted incidence rates of specific adverse events that occurred following initiation of study drug . Results Summary measures of adverse events overall were similar between the sitagliptin and non-exposed ( active comparator or placebo ) groups , except for higher incidences of deaths and drug-related adverse events in the non-exposed group . Incidence rates of specific adverse events were generally similar between the two groups , with the exception of hypoglycemia . A lower incidence rate of hypoglycemia was observed in the sitagliptin group compared with the non-exposed group [ 7.0 vs. 14.3 per 100 patient-years ; difference −7.6 ( 95 % CI −11.2 to −4.3 ] ) , primarily due to greater use of sulfonylureas in the non-exposed group . Conclusions In this pooled safety analysis of elderly patients with type 2 diabetes , treatment with sitagliptin 100 mg/day was generally well tolerated for up to 2 years", "Objective To examine whether established diabetes risk factors and diabetes risk algorithms are associated with future frailty . Design Prospect i ve cohort study . Risk algorithms at baseline ( 1997–1999 ) were the Framingham Offspring , Cambridge , and Finnish diabetes risk scores . Setting Civil service departments in London , United Kingdom . Participants There were 2707 participants ( 72 % men ) aged 45 to 69 years at baseline assessment and free of diabetes . Measurements Risk factors ( age , sex , family history of diabetes , body mass index , waist circumference , systolic and diastolic blood pressure , antihypertensive and corticosteroid treatments , history of high blood glucose , smoking status , physical activity , consumption of fruits and vegetables , fasting glucose , HDL-cholesterol , and triglycerides ) were used to construct the risk algorithms . Frailty , assessed during a resurvey in 2007–2009 , was denoted by the presence of 3 or more of the following indicators : self-reported exhaustion , low physical activity , slow walking speed , low grip strength , and weight loss ; “ prefrailty ” was defined as having 2 or fewer of these indicators . Results After a mean follow-up of 10.5 years , 2.8 % of the sample was classified as frail and 37.5 % as prefrail . Increased age , being female , stopping smoking , low physical activity , and not having a daily consumption of fruits and vegetables were each associated with frailty or prefrailty . The Cambridge and Finnish diabetes risk scores were associated with frailty/prefrailty with odds ratios per 1 SD increase ( disadvantage ) in score of 1.18 ( 95 % confidence interval : 1.09–1.27 ) and 1.27 ( 1.17–1.37 ) , respectively . Conclusion Selected diabetes risk factors and risk scores are associated with subsequent frailty . Risk scores may have utility for frailty prediction in clinical practice", "The sustainability of health and social care systems is threatened by a growing population of older persons with heterogeneous needs related to multimorbidity , frailty , and increased risk of functional impairment . Since disability is difficult to reverse in old age and is extremely burdensome for individuals and society , novel strategies should be devised to preserve adequate levels of function and independence in late life . The development of mobility disability , an early event in the disablement process , precedes and predicts more severe forms of inability . Its prevention is , therefore , critical to impede the transition to overt disability . For this reason , the Sarcopenia and Physical fRailty IN older people : multi-componenT Treatment strategies ( SPRINTT ) project is conducting a r and omized controlled trial ( RCT ) to test a multicomponent intervention ( MCI ) specifically design ed to prevent mobility disability in high-risk older persons . SPRINTT is a phase III , multicenter RCT aim ed at comparing the efficacy of a MCI , based on long-term structured physical activity , nutritional counseling/dietary intervention , and an information and communication technology intervention , versus a healthy aging lifestyle education program design ed to prevent mobility disability in 1500 older persons with physical frailty and sarcopenia who will be followed for up to 36 months . The primary outcome of the SPRINTT trial is mobility disability , operationalized as the inability to walk for 400 m within 15 min , without sitting , help of another person , or the use of a walker . Secondary outcomes include changes in muscle mass and strength , persistent mobility disability , falls and injurious falls , disability in activities of daily living , nutritional status , cognition , mood , the use of healthcare re sources , cost-effectiveness analysis , quality of life , and mortality rate . SPRINTT results are expected to promote significant advancements in the management of frail older persons at high risk of disability from both clinical and regulatory perspectives . The findings are also projected to pave the way for major investments in the field of disability prevention in old age", "AIMS The GERODIAB study is the first French multicentre , prospect i ve , observational study that aims , through a 5-year cohort follow-up , to evaluate the link between glycaemic control and morbidity/mortality of type 2 diabetic ( T2D ) patients aged 70 years and older . This first report describes the study population at inclusion . PATIENTS AND METHODS A total of 987 T2D autonomous patients , aged ≥70 years , were recruited between June 2009 and July 2010 at 56 investigator centres . Their general parameters , diabetes characteristics and st and ard geriatric parameters were recorded . RESULTS The patients ' mean age was 77±5 years , with 65.2 % aged 75 years or more . The mean BMI was close to 30 kg/m(2 ) . Hypertension was found in 89.7 % of patients , and 85.0 % had at least one cholesterol abnormality . The mean duration of the diabetes was around 18 years , and the mean HbA(1c ) level was about 7.5 % . During the previous six months , 33.6 % of patients had experienced one or several hypoglycaemias . Also , 26 % of patients presented with diabetic retinopathy , 37.3 % had a GFR , 31.2 % had coronary insufficiency , 10.1 % had heart failure , 15.8 % had cerebrovascular involvement and 25.6 % had peripheral vascular disease of the lower extremities . In addition , 30.5 % of patients had orthostatic hypotension , 12.4 % had malnutrition and 28.8 % had cognitive impairment , all of which were often diagnosed at inclusion . Three-quarters of patients were taking an oral antidiabetic drug and nearly six in every 10 patients were using insulin . CONCLUSION This population can be considered representative of elderly , autonomous T2D patients , and its follow-up should clarify the link between glycaemic control and mortality/morbidity ", "Aims To compare the efficacy and safety of new insulin glargine 300 U/ml ( Gla-300 ) with that of glargine 100 U/ml ( Gla-100 ) in insulin-naïve people with type 2 diabetes using oral glucose-lowering drugs . Methods The EDITION 3 study was a multicentre , open-label , parallel-group study . Participants were r and omized to Gla-300 or Gla-100 once daily for 6 months , discontinuing sulphonylureas and glinides , with a dose titration aim ed at achieving pre-breakfast plasma glucose concentrations of 4.4–5.6 mmol/l ( 80–100 mg/dl ) . The primary endpoint was change in glycated haemoglobin ( HbA1c ) from baseline to month 6 . The main secondary endpoint was percentage of participants with ≥1 nocturnal confirmed [ ≤3.9 mmol/l ( ≤70 mg/dl ) ] or severe hypoglycaemia from week 9 to month 6 . Other measures of glycaemia and hypoglycaemia , weight change and insulin dose were assessed . Results R and omized participants ( n = 878 ) had a mean ( st and ard deviation ) age of 57.7 ( 10.1 ) years , diabetes duration 9.8 ( 6.4 ) years , body mass index 33.0 ( 6.7 ) kg/m2 and HbA1c 8.54 ( 1.06 ) % [ 69.8 ( 11.6 ) mmol/mol ] . HbA1c levels decreased by equivalent amounts with the two treatments ; the least squares mean difference in change from baseline was 0.04 [ 95 % confidence interval ( CI ) −0.09 to 0.17 ] % or 0.4 ( −1.0 to 1.9 ) mmol/mol . Numerically fewer participants reported ≥1 nocturnal confirmed ( ≤3.9 mmol/l ) or severe hypoglycaemia from week 9 to month 6 [ relative risk ( RR ) 0.89 ( 95 % CI 0.66 to 1.20 ) ] with Gla-300 versus Gla-100 ; a significantly lower risk of hypoglycaemia with this definition was found over the 6-month treatment period [ RR 0.76 ( 95 % CI 0.59 to 0.99 ) ] . No between-treatment differences in adverse events were identified . Conclusions Gla-300 is as effective as Gla-100 in reducing HbA1c in insulin-naïve people with type 2 diabetes , with lower hypoglycaemia risk", "ABSTRACT Accumulating evidence implicates gut microbiota as promising targets for the treatment of type 2 diabetes mellitus ( T2DM ) . With a r and omized clinical trial , we tested the hypothesis that alteration of gut microbiota may be involved in the alleviation of T2DM with hyperlipidemia by metformin and a specifically design ed herbal formula ( AMC ) . Four hundred fifty patients with T2DM and hyperlipidemia were r and omly assigned to either the metformin- or AMC-treated group . After 12 weeks of treatment , 100 patients were r and omly selected from each group and assessed for clinical improvement . The effects of the two drugs on the intestinal microbiota were evaluated by analyzing the V3 and V4 regions of the 16S rRNA gene by Illumina sequencing and multivariate statistical methods . Both metformin and AMC significantly alleviated hyperglycemia and hyperlipidemia and shifted gut microbiota structure in diabetic patients . They significantly increased a coabundant group represented by Blautia spp . , which significantly correlated with the improvements in glucose and lipid homeostasis . However , AMC showed better efficacies in improving homeostasis model assessment of insulin resistance ( HOMA-IR ) and plasma triglyceride and also exerted a larger effect on gut microbiota . Furthermore , only AMC increased the coabundant group represented by Faecalibacterium spp . , which was previously reported to be associated with the alleviation of T2DM in a r and omized clinical trial . Metformin and the Chinese herbal formula may ameliorate type 2 diabetes with hyperlipidemia via enriching beneficial bacteria , such as Blautia and Faecalibacterium spp . IMPORTANCE Metabolic diseases such as T2DM and obesity have become a worldwide public health threat . Accumulating evidence indicates that gut microbiota can causatively arouse metabolic diseases , and thus the gut microbiota serves as a promising target for disease control . In this study , we evaluated the role of gut microbiota during improvements in hyperglycemia and hyperlipidemia by two drugs : metformin and a specifically design ed Chinese herbal formula ( AMC ) for diabetic patients with hyperlipidemia . Both drugs significantly ameliorated blood glucose and lipid levels and shifted the gut microbiota . Blautia spp . were identified as being associated with improvements in glucose and lipid homeostasis for both drugs . AMC exerted larger effects on the gut microbiota together with better efficacies in improving HOMA-IR and plasma triglyceride levels , which were associated with the enrichment of Faecalibacterium spp . In brief , these data suggest that gut microbiota might be involved in the alleviation of diabetes with hyperlipidemia by metformin and the AMC herbal formula . Metabolic diseases such as T2DM and obesity have become a worldwide public health threat . Accumulating evidence indicates that gut microbiota can causatively arouse metabolic diseases , and thus the gut microbiota serves as a promising target for disease control . In this study , we evaluated the role of gut microbiota during improvements in hyperglycemia and hyperlipidemia by two drugs : metformin and a specifically design ed Chinese herbal formula ( AMC ) for diabetic patients with hyperlipidemia . Both drugs significantly ameliorated blood glucose and lipid levels and shifted the gut microbiota . Blautia spp . were identified as being associated with improvements in glucose and lipid homeostasis for both drugs . AMC exerted larger effects on the gut microbiota together with better efficacies in improving HOMA-IR and plasma triglyceride levels , which were associated with the enrichment of Faecalibacterium spp . In brief , these data suggest that gut microbiota might be involved in the alleviation of diabetes with hyperlipidemia by metformin and the AMC herbal formula", "BACKGROUND For patients with type 2 diabetes who do not achieve target glycaemic control with conventional insulin treatment , advancing to a basal-bolus insulin regimen is often recommended . We aim ed to compare the efficacy and safety of long-acting glucagon-like peptide-1 receptor agonist dulaglutide with that of insulin glargine , both combined with pr and ial insulin lispro , in patients with type 2 diabetes . METHODS We did this 52 week , r and omised , open-label , phase 3 , non-inferiority trial at 105 study sites in 15 countries . Patients ( aged ≥18 years ) with type 2 diabetes inadequately controlled with conventional insulin treatment were r and omly assigned ( 1:1:1 ) , via a computer-generated r and omisation sequence with an interactive voice-response system , to receive once-weekly dulaglutide 1·5 mg , dulaglutide 0·75 mg , or daily bedtime glargine . R and omisation was stratified by country and metformin use . Participants and study investigators were not masked to treatment allocation , but were unaware of dulaglutide dose assignment . The primary outcome was a change in glycated haemoglobin A1c ( HbA1c ) from baseline to week 26 , with a 0·4 % non-inferiority margin . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT01191268 . FINDINGS Between Dec 9 , 2010 , and Sept 21 , 2012 , we r and omly assigned 884 patients to receive dulaglutide 1·5 mg ( n=295 ) , dulaglutide 0·75 mg ( n=293 ) , or glargine ( n=296 ) . At 26 weeks , the adjusted mean change in HbA1c was greater in patients receiving dulaglutide 1·5 mg ( -1·64 % [ 95 % CI -1·78 to -1·50 ] , -17·93 mmol/mol [ -19·44 to -16·42 ] ) and dulaglutide 0·75 mg ( -1·59 % [ -1·73 to -1·45 ] , -17·38 mmol/mol [ -18·89 to -15·87 ] ) than in those receiving glargine ( -1·41 % [ -1·55 to -1·27 ] , -15·41 mmol/mol [ -16·92 to -13·90 ] ) . The adjusted mean difference versus glargine was -0·22 % ( 95 % CI -0·38 to -0·07 , -2·40 mmol/mol [ -4·15 to -0·77 ] ; p=0·005 ) for dulaglutide 1·5 mg and -0·17 % ( -0·33 to -0·02 , -1·86 mmol/mol [ -3·61 to -0·22 ] ; p=0·015 ) for dulaglutide 0·75 mg . Five ( septicaemia ( n=1 in the dulaglutide 1·5 mg group ) ; pneumonia ( n=1 in the dulaglutide 0·75 mg group ) ; cardiogenic shock ; ventricular fibrillation ; and an unknown cause ( n=3 in the glargine group ) . We recorded serious adverse events in 27 ( 9 % ) patients in the dulaglutide 1·5 mg group , 44 ( 15 % ) patients in the dulaglutide 0·75 mg group , and 54 ( 18 % ) patients in the glargine group . The most frequent adverse events , arising more often with dulaglutide than glargine , were nausea , diarrhoea , and vomiting . INTERPRETATION Dulaglutide in combination with lispro result ed in a significantly greater improvement in glycaemic control than did glargine and represents a new treatment option for patients unable to achieve glycaemic targets with conventional insulin treatment . FUNDING Eli Lilly and Company", "Background : Dapagliflozin is a sodium‐glucose co‐transporter‐2 ( SGLT‐2 ) inhibitor that reduces blood glucose in patients with type 2 diabetes mellitus ( T2DM ) by promoting glycosuria via inhibiting urinary glucose reabsorption . In addition to improving blood glucose control , treatment with dapagliflozin results in glucose‐induced osmotic diuresis , weight loss , and blood pressure lowering . Previous trials of SGLT‐2 inhibitors showed reductions in cardiovascular ( CV ) events , including CV death and hospitalization for heart failure , and ischemic events in patients with atherosclerotic cardiovascular disease ( ASCVD ) . Research design and methods : DECLARE – TIMI 58 ( NCT01730534 ) is a phase 3b r and omized , double‐blind , placebo‐controlled trial design ed to evaluate the CV safety and efficacy of dapagliflozin that has completed r and omization of 17,160 patients with T2DM and a history of either established ASCVD ( n = 6,971 ) or multiple risk factors for ASCVD ( n = 10,189 ) . Patients were r and omized in a 1:1 fashion to dapagliflozin 10 mg or matching placebo . The primary safety outcome is the time to the first event of the composite of CV death , myocardial infa rct ion , or ischemic stroke ( major adverse cardiovascular events ; MACEs ) . The co‐ primary efficacy outcomes are the composite of CV death , myocardial infa rct ion , or ischemic stroke and the composite of CV death or hospitalization for heart failure . This event‐driven trial will continue until at least 1,390 subjects have a MACE outcome , thereby providing > 99 % power to test for the primary outcome of safety of dapagliflozin measured by rejecting the hypothesis that the upper bound of the CI > 1.3 for the primary outcome of MACE , as well as 85 % power to detect a 15 % relative risk reduction in MACE and an estimated 87 % power to detect a 20 % reduction in the composite of CV death or hospitalization for heart failure at a 1‐sided & agr ; level of .0231 . Conclusion : The DECLARE – TIMI 58 trial is testing the hypotheses that dapagliflozin is safe ( does not increase ) and may reduce the occurrence of major CV events . DECLARE – TIMI 58 is the largest study to address this question with an SGLT‐2 inhibitor in patients with T2DM and with established CV disease and without CV disease but with multiple risk factors ", "AIMS To assess initial pharmacotherapy of Type 2 diabetes with the sodium-glucose cotransporter-2 inhibitor dapagliflozin . METHODS This double-blind , placebo-controlled trial , r and omly allocated people with Type 2 diabetes aged 18 - 77 years and inadequate glycaemic control on diet and exercise [ HbA1c 53 - 86 mmol/mol ( 7.0 - 10.0 % ) ] to receive placebo ( n = 75 ) or dapagliflozin monotherapy 2.5 mg ( n = 65 ) , 5 mg ( n = 64 ) or 10 mg ( n = 70 ) once daily in the morning . After 24 weeks , low-dose double-blind metformin 500 mg/day was added to the placebo group regimen ( placebo+low-dose metformin group ) . Changes in HbA1c level , fasting plasma glucose and body weight , as well as adverse events , were assessed over 102 weeks . RESULTS Of the 274 participants r and omized , 167 completed the study ( 60.9 % ) . At 102 weeks , significant differences vs placebo+low-dose metformin with dapagliflozin 5 and 10 mg were observed for HbA1c ( -5.8 mmol/mol [ -0.53 % ] , P = 0.018 ; and -4.8 mmol/mol [ -0.44 % ] , P = 0.048 ) , respectively ) ; and for FPG ( -0.69 mmol/L , P = 0.044 ; and -1.12 mmol/l , P = 0.001 , respectively ) . For body weight , the difference between the dapagliflozin 10-mg group and the placebo+low-dose metformin group was significant ( -2.60 kg ; P = 0.016 ) . Hypoglycaemic events were uncommon , with rates of 5.3 % for placebo+low-dose metformin group and 0 - 4.6 % for the dapagliflozin groups . Genital infections and urinary tract infections were more common in the dapagliflozin groups than in the placebo+low-dose metformin group . CONCLUSIONS Dapagliflozin as monotherapy in treatment-naïve people with early Type 2 diabetes improved glycaemic control and reduced weight without increasing hypoglycaemia over 102 weeks . Dapagliflozin may provide an alternative initial pharmacotherapy in such people", "BACKGROUND The effects of empagliflozin , an inhibitor of sodium-glucose cotransporter 2 , in addition to st and ard care , on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known . METHODS We r and omly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily . The primary composite outcome was death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke , as analyzed in the pooled empagliflozin group versus the placebo group . The key secondary composite outcome was the primary outcome plus hospitalization for unstable angina . RESULTS A total of 7020 patients were treated ( median observation time , 3.1 years ) . The primary outcome occurred in 490 of 4687 patients ( 10.5 % ) in the pooled empagliflozin group and in 282 of 2333 patients ( 12.1 % ) in the placebo group ( hazard ratio in the empagliflozin group , 0.86 ; 95.02 % confidence interval , 0.74 to 0.99 ; P=0.04 for superiority ) . There were no significant between-group differences in the rates of myocardial infa rct ion or stroke , but in the empagliflozin group there were significantly lower rates of death from cardiovascular causes ( 3.7 % , vs. 5.9 % in the placebo group ; 38 % relative risk reduction ) , hospitalization for heart failure ( 2.7 % and 4.1 % , respectively ; 35 % relative risk reduction ) , and death from any cause ( 5.7 % and 8.3 % , respectively ; 32 % relative risk reduction ) . There was no significant between-group difference in the key secondary outcome ( P=0.08 for superiority ) . Among patients receiving empagliflozin , there was an increased rate of genital infection but no increase in other adverse events . CONCLUSIONS Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin , as compared with placebo , had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to st and ard care . ( Funded by Boehringer Ingelheim and Eli Lilly ; EMPA-REG OUTCOME Clinical Trials.gov number , NCT01131676 . )", "BACKGROUND Cardiovascular morbidity and mortality are higher among patients with type 2 diabetes , particularly those with concomitant cardiovascular diseases , than in most other population s. We assessed the effects of lixisenatide , a glucagon-like peptide 1-receptor agonist , on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event . METHODS We r and omly assigned patients with type 2 diabetes who had had a myocardial infa rct ion or who had been hospitalized for unstable angina within the previous 180 days to receive lixisenatide or placebo in addition to locally determined st and ards of care . The trial was design ed with adequate statistical power to assess whether lixisenatide was noninferior as well as superior to placebo , as defined by an upper boundary of the 95 % confidence interval for the hazard ratio of less than 1.3 and 1.0 , respectively , for the primary composite end point of cardiovascular death , myocardial infa rct ion , stroke , or hospitalization for unstable angina . RESULTS The 6068 patients who underwent r and omization were followed for a median of 25 months . A primary end-point event occurred in 406 patients ( 13.4 % ) in the lixisenatide group and in 399 ( 13.2 % ) in the placebo group ( hazard ratio , 1.02 ; 95 % confidence interval [ CI ] , 0.89 to 1.17 ) , which showed the noninferiority of lixisenatide to placebo ( P rate of hospitalization for heart failure ( hazard ratio in the lixisenatide group , 0.96 ; 95 % CI , 0.75 to 1.23 ) or the rate of death ( hazard ratio , 0.94 ; 95 % CI , 0.78 to 1.13 ) . Lixisenatide was not associated with a higher rate of serious adverse events or severe hypoglycemia , pancreatitis , pancreatic neoplasms , or allergic reactions than was placebo . CONCLUSIONS In patients with type 2 diabetes and a recent acute coronary syndrome , the addition of lixisenatide to usual care did not significantly alter the rate of major cardiovascular events or other serious adverse events . ( Funded by Sanofi ; ELIXA Clinical Trials.gov number , NCT01147250 . )", "Background Canagliflozin is a sodium – glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure , body weight , and albuminuria in people with diabetes . We report the effects of treatment with canagliflozin on cardiovascular , renal , and safety outcomes . Methods The CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk . Participants in each trial were r and omly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks . The primary outcome was a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . Results The mean age of the participants was 63.3 years , 35.8 % were women , the mean duration of diabetes was 13.5 years , and 65.6 % had a history of cardiovascular disease . The rate of the primary outcome was lower with canagliflozin than with placebo ( occurring in 26.9 vs. 31.5 participants per 1000 patient‐years ; hazard ratio , 0.86 ; 95 % confidence interval [ CI ] , 0.75 to 0.97 ; P canagliflozin with respect to the progression of albuminuria ( hazard ratio , 0.73 ; 95 % CI , 0.67 to 0.79 ) and the composite outcome of a sustained 40 % reduction in the estimated glomerular filtration rate , the need for renal‐replacement therapy , or death from renal causes ( hazard ratio , 0.60 ; 95 % CI , 0.47 to 0.77 ) . Adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation ( 6.3 vs. 3.4 participants per 1000 patient‐years ; hazard ratio , 1.97 ; 95 % CI , 1.41 to 2.75 ) ; amputations were primarily at the level of the toe or metatarsal . Conclusions In two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease , patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation , primarily at the level of the toe or metatarsal . ( Funded by Janssen Research and Development ; CANVAS and CANVAS‐R Clinical Trials.gov numbers , NCT01032629 and NCT01989754 , respectively .", "BACKGROUND Obesity causes frailty in older adults ; however , weight loss might accelerate age‐related loss of muscle and bone mass and result ant sarcopenia and osteopenia . METHODS In this clinical trial involving 160 obese older adults , we evaluated the effectiveness of several exercise modes in reversing frailty and preventing reduction in muscle and bone mass induced by weight loss . Participants were r and omly assigned to a weight‐management program plus one of three exercise programs — aerobic training , resistance training , or combined aerobic and resistance training — or to a control group ( no weight‐management or exercise program ) . The primary outcome was the change in Physical Performance Test score from baseline to 6 months ( scores range from 0 to 36 points ; higher scores indicate better performance ) . Secondary outcomes included changes in other frailty measures , body composition , bone mineral density , and physical functions . RESULTS A total of 141 participants completed the study . The Physical Performance Test score increased more in the combination group than in the aerobic and resistance groups ( 27.9 to 33.4 points [ 21 % increase ] vs. 29.3 to 33.2 points [ 14 % increase ] and 28.8 to 32.7 points [ 14 % increase ] , respectively ; P=0.01 and P=0.02 after Bonferroni correction ) ; the scores increased more in all exercise groups than in the control group ( P comparisons ) . Peak oxygen consumption ( milliliters per kilogram of body weight per minute ) increased more in the combination and aerobic groups ( 17.2 to 20.3 [ 17 % increase ] and 17.6 to 20.9 [ 18 % increase ] , respectively ) than in the resistance group ( 17.0 to 18.3 [ 8 % increase ] ) ( P comparisons ) . Strength increased more in the combination and resistance groups ( 272 to 320 kg [ 18 % increase ] and 288 to 337 kg [ 19 % increase ] , respectively ) than in the aerobic group ( 265 to 270 kg [ 4 % increase ] ) ( P both comparisons ) . Body weight decreased by 9 % in all exercise groups but did not change significantly in the control group . Lean mass decreased less in the combination and resistance groups than in the aerobic group ( 56.5 to 54.8 kg [ 3 % decrease ] and 58.1 to 57.1 kg [ 2 % decrease ] , respectively , vs. 55.0 to 52.3 kg [ 5 % decrease ] ) , as did bone mineral density at the total hip ( grams per square centimeter ; 1.010 to 0.996 [ 1 % decrease ] and 1.047 to 1.041 [ 0.5 % decrease ] , respectively , vs. 1.018 to 0.991 [ 3 % decrease ] ) ( P comparisons ) . Exercise‐related adverse events included musculoskeletal injuries . CONCLUSIONS Of the methods tested , weight loss plus combined aerobic and resistance exercise was the most effective in improving functional status of obese older adults . ( Funded by the National Institutes of Health ; LITOE Clinical Trials.gov number , NCT01065636 .", "BACKGROUND There is emerging evidence of the role of diabetes as a risk factor for frailty . However , the mechanisms of this association are uncertain . METHODS Prospect i ve cohort study of 1750 noninstitutionalized individuals aged 60 years or older recruited in 2008 - 2010 . At baseline , information was obtained on health behaviors , morbidity , cardiometabolic biomarkers , and antidiabetic treatments . Individuals were considered diabetic if they reported a physician diagnosis or had fasting serum glucose of 126 mg/dL or higher . Study participants were followed through 2012 to assess incident frailty , defined as at least 3 of the 5 Fried criteria . RESULTS At baseline , the cohort included 346 individuals with diabetes and 1404 without diabetes . Over a mean 3.5-year follow-up , 115 cases of incident frailty were ascertained . After adjustment for age , sex , and education , participants with diabetes showed an increased risk of frailty ( odds ratio [ OR ] 2.18 , 95 % confidence interval [ CI ] 1.42 - 3.37 ) . Additional adjustment for health behaviors and abdominal obesity yielded a 29.7 % reduction in the OR ( OR 1.83 , 95 % CI 1.16 - 2.90 ) . Subsequent adjustment for morbidity produced an additional 8.4 % reduction ( OR 1.76 , 95 % CI 1.10 - 2.82 ) , and for cardiometabolic biomarkers , a further 44 % reduction ( OR 1.32 , 95 % CI 0.70 - 2.49 ) . In particular , adjustment for HbA1c , lipoproteins , and triglycerides accounted for the greatest reductions . Finally , additional adjustment for oral antidiabetic medication reduced the OR to 1.01 ( 95 % CI 0.46 - 2.20 ) , whereas adjustment for nutritional therapy increased the OR to 1.64 ( 95 % CI 0.77 - 3.49 ) . CONCLUSIONS Diabetes mellitus is associated with higher risk of frailty ; this association is partly explained by unhealthy behaviors and obesity and , to a greater extent , by poor glucose control and altered serum lipid profile among diabetic individuals . Conversely , diabetes nutritional therapy reduces the risk of frailty ", "OBJECTIVE To compare the efficacy and safety of new insulin glargine 300 units/mL ( Gla-300 ) with glargine 100 units/mL ( Gla-100 ) in people with type 2 diabetes using basal insulin ( ≥42 units/day ) plus oral antihyperglycemic drugs ( OADs ) . RESEARCH DESIGN AND METHODS EDITION 2 was a multicenter , open-label , two-arm study . Adults receiving basal insulin plus OADs were r and omized to Gla-300 or Gla-100 once daily for 6 months . The primary end point was change in HbA1c . The main secondary end point was percentage of participants with one or more nocturnal confirmed ( ≤3.9 mmol/L [ ≤70 mg/dL ] ) or severe hypoglycemic events from week 9 to month 6 . RESULTS R and omized participants ( n = 811 ) had a mean ( SD ) HbA1c of 8.24 % ( 0.82 ) and BMI of 34.8 kg/m2 ( 6.4 ) . Glycemic control improved similarly with both basal insulins ; least squares mean ( SD ) reduction from baseline was −0.57 % ( 0.09 ) for Gla-300 and −0.56 % ( 0.09 ) for Gla-100 ( mean difference −0.01 % [ 95 % CI −0.14 to 0.12 ] ) , with 10 % higher dose of Gla-300 . Less nocturnal confirmed ( ≤3.9 mmol/L [ ≤70 mg/dL ] ) or severe hypoglycemia was observed with Gla-300 from week 9 to month 6 ( relative risk 0.77 [ 95 % CI 0.61–0.99 ] ; P = 0.038 ) and during the first 8 weeks . Fewer nocturnal and any time ( 24 h ) hypoglycemic events were reported during the entire 6-month period . Weight gain was lower with Gla-300 than with Gla-100 ( P = 0.015 ) . No between-treatment differences in safety parameters were identified . CONCLUSIONS Gla-300 was as effective as Gla-100 and associated with a lower risk of hypoglycemia during the night and at any time of the day", "Background : Canagliflozin is a sodium glucose cotransporter 2 inhibitor that significantly reduces the composite of cardiovascular death , nonfatal myocardial infa rct ion , or nonfatal stroke in patients with type 2 diabetes mellitus and elevated cardiovascular risk . The comparative effects among participants with and without a history of cardiovascular disease ( secondary versus primary prevention ) were prespecified for evaluation . Methods : The CANVAS Program ( Canagliflozin Cardiovascular Assessment Study ) r and omly assigned 10 142 participants with type 2 diabetes mellitus to canagliflozin or placebo . The primary prevention cohort comprised individuals ≥50 years of age with ≥2 risk factors for cardiovascular events but with no prior cardiovascular event , and the secondary prevention cohort comprised individuals ≥30 years of age with a prior cardiovascular event . The primary end point was a composite of cardiovascular death , nonfatal myocardial infa rct ion , or nonfatal stroke . Secondary outcomes included heart failure hospitalization and a renal composite ( 40 % reduction in estimated glomerular filtration rate , renal replacement therapy , or renal death ) . Results : Primary prevention participants ( N=3486 ; 34 % ) were younger ( 63 versus 64 years of age ) , were more often female ( 45 % versus 31 % ) , and had a longer duration of diabetes mellitus ( 14 versus 13 years ) compared with secondary prevention participants ( N=6656 ; 66 % ) . The primary end point event rate was higher in the secondary prevention group compared with the primary prevention group ( 36.9 versus 15.7/1000 patient-years , P with canagliflozin compared with placebo ( 26.9 versus 31.5/1000 patient-years ; hazard ratio [ HR ] , 0.86 ; 95 % confidence interval [ CI ] , 0.75–0.97 ; P cohorts . Renal outcomes ( HR , 0.59 ; 95 % CI , 0.44–0.79 versus HR , 0.63 ; 95 % CI , 0.39–1.02 ; interaction P value=0.73 ) and heart failure hospitalization ( HR , 0.68 ; 95 % CI , 0.51–0.90 versus HR , 0.64 ; 95 % CI , 0.35–1.15 ; interaction P value=0.91 ) were similarly reduced in the secondary and primary prevention cohorts , respectively . Lower extremity amputations were similarly increased in the secondary and primary prevention cohorts ( HR , 2.07 ; 95 % CI , 1.43–3.00 versus HR , 1.52 ; 95 % CI , 0.70–3.29 ; interaction P value=0.63 ) . Conclusions : Patients with type 2 diabetes mellitus and prior cardiovascular events had higher rates of cardiovascular outcomes compared with the primary prevention patients . Canagliflozin reduced cardiovascular and renal outcomes with no statistical evidence of heterogeneity of the treatment effect across the primary and secondary prevention groups . Additional studies will provide further insights into the effects of canagliflozin in these patient population s. Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifiers : NCT01032629 and NCT01989754" ]	41189c30-06ff-11f0-808a-c43d1ab1c353
It is speculated that lifestyle interventions known to improve diabetic metabolic state may exert their effects via adipokines . The aim of this systematic review and meta- analysis was to evaluate the chronic effects of physical exercise on adiponectin and leptin levels in adult prediabetic and diabetic individuals . PubMed , Embase , Scopus , The Cochrane Library , clinical trials.gov , and WHO Clinical Trials Registry were search ed for r and omized controlled trials . Pooled effects of interventions were assessed as mean difference ( MD ) with r and om effects model . Sensitivity analysis was conducted to test data robustness and subgroup analysis for study heterogeneity . Twenty-two trials with 2996 individuals were included in the meta- analysis . Physical exercise increased levels of adiponectin ( MD : 0.42 µg/mL ; 95 % confidence interval ( CI ) , 0.23 , 0.60 , p and reduced leptin levels ( MD : −1.89 ng/mL ; 95 % CI , −2.64 , −1.14 , p Study heterogeneity was generally high . As for physical exercise modalities , aerobic exercise , but not other modalities , increased adiponectin and reduced leptin levels . In conclusion , physical exercise and , specifically , aerobic exercise , leads to higher adiponectin and lower leptin levels in prediabetic and diabetic adults . However , cautious interpretation of current findings is warranted	[ "OBJECTIVE This study investigated whether fitness changes result ing from lifestyle interventions for weight loss may independently contribute to the improvement of low adiponectin levels in obese individuals with diabetes . RESEARCH DESIGN AND METHODS Look AHEAD ( Action for Health in Diabetes ) r and omized overweight/obese individuals with type 2 diabetes to intensive lifestyle intervention ( ILI ) for weight loss or to diabetes support and education ( DSE ) . Total and high – molecular weight adiponectin ( adiponectins ) , weight , and cardiorespiratory fitness ( submaximal exercise stress test ) were measured in 1,397 participants at baseline and at 1 year , when ILI was most intense . Regression analyses examined the associations of 1-year weight and fitness changes with change in adiponectins . RESULTS ILI result ed in greater improvements in weight , fitness , and adiponectins at 1 year compared with DSE ( P Weight loss and improved fitness were each associated with changes in adiponectins in men and women ( P Weight loss contributed an additional 4–5 % to the variance of change in adiponectins than did increased fitness in men ; in women , the contributions of improved fitness ( 1 % greater ) and of weight loss were similar . When weight and fitness changes were both accounted for , weight loss in men and increased fitness in women retained their strong associations ( P Improvements in fitness and weight with ILI were favorably but distinctly associated with changes in adiponectin levels in overweight/obese men and women with diabetes . Future studies need to investigate whether sex-specific biological determinants contribute to the observed associations", "Recent guidelines on exercise for weight loss and weight maintenance include resistance training as part of the exercise prescription . Yet few studies have compared the effects of similar amounts of aerobic and resistance training on body mass and fat mass in overweight adults . STRRIDE AT/RT , a r and omized trial , compared aerobic training , resistance training , and a combination of the two to determine the optimal mode of exercise for obesity reduction . Participants were 119 sedentary , overweight or obese adults who were r and omized to one of three 8-mo exercise protocol s : 1 ) RT : resistance training , 2 ) AT : aerobic training , and 3 ) AT/RT : aerobic and resistance training ( combination of AT and RT ) . Primary outcomes included total body mass , fat mass , and lean body mass . The AT and AT/RT groups reduced total body mass and fat mass more than RT ( P lean body mass more than AT ( P AT and RT did not result in significantly more fat mass or body mass reductions over AT alone . Balancing time commitments against health benefits , it appears that AT is the optimal mode of exercise for reducing fat mass and body mass , while a program including RT is needed for increasing lean mass in middle-aged , overweight/obese individuals", "BACKGROUND In a r and omized , controlled , 2 x 2 factorial trial on the effect of long-term changes in diet and exercise , a significant reduction in body weight and fat mass was observed . Alterations in leptin and plasminogen activator inhibitor-1 concentrations were previously reported from this study . OBJECTIVE We examined the separate and combined effects of a 1-y exercise and diet intervention on several adipokines ; adiponectin , interleukin-6 and -8 , tumor necrosis factor-alpha , monocyte chemoattractant protein-1 , hepatocyte growth factor , nerve growth factor , C-reactive protein , and resistin . DESIGN One hundred eighty-eight men with several risk factors for diabetes and cardiovascular disease were r and omly allocated to 4 groups : diet , exercise , combined diet and exercise , and control . RESULTS Plasma adiponectin concentrations remained unchanged , whereas body mass index and fat mass decreased after dietary changes and an increase in physical activity . In the control group , adiponectin concentrations were reduced . Analyzed according to the factorial design , only diet intervention had a significant ( P = 0.03 ) positive effect on plasma adiponectin relative to control , and this effect was largely explained by changes in fat mass . After adjustment for change in percentage body fat , there were significant positive effects on tumor necrosis factor-alpha in all 3 intervention groups ( P = 0.01 for the diet group , 0.03 for the exercise group , and 0.05 for the combined diet and exercise group ) . Minor changes were observed for the other adipokines . Neither baseline concentrations of nor changes in adiponectin and plasminogen activator inhibitor-1 were significantly correlated to the other adipokines , whereas concentrations of and changes in the other adipokines were significantly correlated . CONCLUSION Diet intervention had a significant positive effect on adiponectin concentrations , which is largely explained by a reduction in fat mass", "Type 2 diabetes ( T2D ) is an age-related chronic disease associated with metabolic dysregulation , chronic inflammation , and activation of peripheral blood mononuclear cells ( P BMC ) . The aim of this study was to assess the effects of a concurrent exercise training program on inflammatory status and metabolic parameters of T2D patients . Sixteen male patients ( age range 55–70 ) were r and omly assigned to an intervention group ( n = 8) , which underwent a concurrent aerobic and resistance training program ( 3 times a week ; 16 weeks ) , or to a control group , which followed physicians ' usual diabetes care advices . Training intervention significantly improved patients ' body composition , blood pressure , total cholesterol , and overall fitness level . After training , plasma levels of adipokines leptin ( −33.9 % ) and RBP4 ( −21.3 % ) , and proinflammatory markers IL-6 ( −25.3 % ) , TNF-α ( −19.8 % ) and MCP-1 ( −15.3 % ) decreased , whereas anabolic hormone IGF-1 level increased ( + 16.4 % ) . All improvements were significantly greater than those of control patients . Plasma proteomic profile of exercised patients showed a reduction of immunoglobulin K light chain and fibrinogen as well . Training also induced a modulation of IL-6 , IGF-1 , and IGFBP-3 mRNAs in the P BMC s. These findings confirm that concurrent aerobic and resistance training improves T2D-related metabolic abnormalities and has the potential to reduce the deleterious health effects of diabetes-related inflammation", "BACKGROUND Diabetes is the most important cause of peripheral neuropathy ( DPN ) . No definitive treatment for DPN has been established , and very few data on the role of exercise training on DPN have been reported . AIM OF THE STUDY We sought to examine the effects of long-term exercise training on the development of DPN in both Types 1 and 2 diabetic patients . PARTICIPANTS AND METHODS Seventy-eight diabetic patients without signs and symptoms of peripheral DPN were enrolled , r and omized , and subdivided in two groups : 31 diabetic participants [ 15 f , 16 m ; 49+/-15.5 years old ; body mass index ( BMI ) = 27.9+/-4.7 ] , who performed a prescribed and supervised 4 h/week brisk walking on a treadmill at 50 % to 85 % of the heart rate reserve ( exercise group : EXE ) , and a control group of 47 diabetic participants ( CON ; 24 f , 23 m ; 52.9+/-13.4 years old ; BMI = 30.9+/-8.4 ) . Vibration perception threshold ( VPT ) , nerve distal latency ( DL ) , nerve conduction velocity ( NCV ) , and nerve action potential amplitude ( NAPA ) in the lower limbs were measured . RESULTS We found significant differences on Delta ( delta ) in NCV for both peroneal and sural motor nerve between the EXE and CON groups during the study period ( P motor neuropathy and sensory neuropathy during the 4 years of the study was significantly higher in the CON than the EXE group ( 17 % vs. 0.0 % , P increased VPT ( 25 V ) during the study was significantly higher in the CON than the EXE group ( 21.3 % vs. 12.9 % , P Change on Hallux VPT from baseline to the end of the study was significantly different between the EXE and CON groups ( P Malleolus VPT between the two groups occurred . CONCLUSIONS This study suggests , for the first time , that long-term aerobic exercise training can prevent the onset or modify the natural history of DPN", "This study examined the independent and combined effects of diet and exercise on adipocytokine and inflammatory cytokines in postmenopausal women with type 2 diabetes . Using a r and omized , controlled design , 33 women ( age , 50 - 70 years ) were assigned to diet alone ( D ) , exercise alone ( EX ) , or diet + exercise ( D + E ) for 14 weeks . Before and after the interventions , blood sample s for adipocytokines and inflammatory markers were drawn , a meal test was performed , and abdominal fat distribution was measured by magnetic resonance imaging ( MRI ) . Body weight decreased approximately 4.5 + /- 0.6 kg ( P D + E interventions , whereas only small changes in body weight were found with the exercise-alone intervention . Plasma C-reactive protein levels were decreased by approximately 15 % with all 3 interventions , whereas leptin levels were reduced with the D and D + E intervention ( D : pre = 48.7 + /- 6.0 , post = 38.9 + /- 5.0 ng/mL ; D + E : pre = 38.5 + /- 6.0 , post = 22.9 + /- 5.0 ng/mL ; P leptin levels to decrease in the EX group ( P = .06 ) . Plasma resistin levels were not altered by the 3 interventions from pre- to posttreatment ( D : pre = 6.9 + /- 0.6 , post = 6.2 + /- 0.4 ng/mL ; D + E : pre = 5.6 + /- 0.6 , post = 5.7 + /- 0.4 ng/mL ; E : pre = 6.2 + /- 0.6 , post = 5.9 + /- 0.6 ng/mL , P > .05 ) , and no differences in adiponectin and tumor necrosis factor alpha ( TNF- alpha ) levels were found . Visceral adipose tissue and tumor necrosis factor alpha were the only predictors of calculated insulin resistance ( P adipocytokines and inflammatory cytokines in older women with type 2 diabetes , suggesting that dramatic weight loss or clinical interventions are needed", "OBJECTIVE —We investigated whether circulating adipokine concentrations can be altered by lifestyle intervention according to general recommendations in subjects at risk for diabetes as well as the potential of leptin , adiponectin , and resistin as biomarkers for lifestyle-induced improvements in glucose metabolism and insulin resistance . RESEARCH DESIGN AND METHODS —In the Study on Lifestyle intervention and Impaired glucose tolerance Maastricht , 147 men and women with impaired glucose tolerance ( IGT ) were r and omized to either a combined diet- and -exercise intervention or a control program . At baseline and after 1 year , an oral glucose tolerance test , an exercise test , and anthropometric measurements were performed . After 1 year , complete data of 103 subjects ( 50 intervention and 53 control subjects ) were obtained . RESULTS —Lifestyle intervention reduced plasma leptin concentrations ( −14.2 % ) in IGT subjects but did not alter plasma adiponectin ( −0.3 % ) or resistin ( −6.5 % ) concentrations despite marked improvements in glucose tolerance and insulin resistance . CONCLUSIONS —Changes in leptin concentration were related to improvements in insulin sensitivity independent of changes in body composition", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "CONTEXT Exercise guidelines for individuals with diabetes include both aerobic and resistance training although few studies have directly examined this exercise combination . OBJECTIVE To examine the benefits of aerobic training alone , resistance training alone , and a combination of both on hemoglobin A(1c ) ( HbA(1c ) ) in individuals with type 2 diabetes . DESIGN , SETTING , AND PARTICIPANTS A r and omized controlled trial in which 262 sedentary men and women in Louisiana with type 2 diabetes and HbA(1c ) levels of 6.5 % or higher were enrolled in the 9-month exercise program between April 2007 and August 2009 . INTERVENTION Forty-one participants were assigned to the nonexercise control group , 73 to resistance training 3 days a week , 72 to aerobic exercise in which they expended 12 kcal/kg per week ; and 76 to combined aerobic and resistance training in which they expended 10 kcal/kg per week and engaged in resistance training twice a week . Main Outcome Change in HbA(1c ) level . Secondary outcomes included measures of anthropometry and fitness . RESULTS The study included 63.0 % women and 47.3 % nonwhite participants who were a mean ( SD ) age of 55.8 years ( 8.7 years ) with a baseline HbA(1c ) level of 7.7 % ( 1.0 % ) . Compared with the control group , the absolute mean change in HbA(1c ) in the combination training exercise group was -0.34 % ( 95 % confidence interval [ CI ] , -0.64 % to -0.03 % ; P = .03 ) . The mean changes in HbA(1c ) were not statistically significant in either the resistance training ( -0.16 % ; 95 % CI , -0.46 % to 0.15 % ; P = .32 ) or the aerobic ( -0.24 % ; 95 % CI , -0.55 % to 0.07 % ; P = .14 ) groups compared with the control group . Only the combination exercise group improved maximum oxygen consumption ( mean , 1.0 mL/kg per min ; 95 % CI , 0.5 - 1.5 , P reduced waist circumference from -1.9 to -2.8 cm compared with the control group . The resistance training group lost a mean of -1.4 kg fat mass ( 95 % CI , -2.0 to -0.7 kg ; P combination training group lost a mean of -1.7 ( -2.3 to -1.1 kg ; P patients with type 2 diabetes mellitus , a combination of aerobic and resistance training compared with the nonexercise control group improved HbA(1c ) levels . This was not achieved by aerobic or resistance training alone . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00458133", "Background Inflammation plays a major role in diabetes‐associated cardiovascular disease ( CVD ) . There is uncertainty whether diet and physical activity interventions can be successfully integrated into healthcare setting s and reduce markers of inflammation and risk of CVD in patients with type 2 diabetes ( T2D ) . Methods and Results Systemic markers of inflammation were determined in a 12‐month , real‐world , multicenter , r and omized , controlled trial that investigated the effect of diet , diet plus physical activity , and usual care in 593 individuals with newly diagnosed T2D . During the first 6 months , serum C‐reactive protein ( CRP ) improved by −21 ( −36 to −1.4)% and −22 ( −38 to −3.1)% in diet and diet plus physical activity arms versus usual care . There were also improvements in adiponectin and soluble intercellular adhesion molecule‐1 ( sICAM‐1 ) . Though medication‐adjusted CRP was improved between 6 and 12 months for usual care , both interventions were more successful in reducing the relative risk of a high‐risk CRP level of > 3 mg/L ( risk ratios of 0.72 [ 0.55 to 0.95 ] for diet versus usual care and 0.67 [ 0.50 to 0.90 ] for diet plus activity versus usual care ) . Furthermore , sICAM‐1 ( a marker of vascular risk ) , remained substantially lower than usual care in both intervention arms at 12 months . Conclusions Motivational , unsupervised diet and /or diet plus physical activity interventions given soon after diagnosis in real‐world healthcare setting s improve markers of inflammation and cardiovascular risk in patients with T2D , even after accounting for the effect of adjustments to medication to try and control blood pressure , glycated hemoglobin , and lipids . Clinical Trial Registration URL : http://www.controlled-trials.com/. Unique identifier : IS RCT N92162869", "Aims . To examine one-year changes in oxidative damage and inflammation level in type 2 diabetic patients undergoing behavioral treatment for subsyndromal depression . Material s and Methods . A r and omized controlled comparison of psychoeducation ( A ) , physical exercise ( B ) , and enhanced treatment as usual ( C ) was performed in 209 eligible subjects in a tertiary diabetes care setting . Depressive symptoms ( primary outcome ) and selected biomarkers of oxidative damage and inflammation ( secondary outcomes ) were assessed at baseline and six- and twelve-month follow-up . Results . Out of the 74 , 67 , and 68 patients r and omised into groups A , B , and C , respectively , 201 completed the interventions , and 179 were analysed . Participants in all three groups equally improved in depressive symptoms from baseline to one-year follow-up ( repeated measures ANOVA ; F = 12.51 , p 0.07 ) . Urinary 8-oxo-deoxyguanosine ( u-8-oxodG ) decreased ( F = 10.66 , p did sialic acid and leukocytes ( F = 84.57 , η 2 = 0.32 and F = 12.61 , η 2 = 0.07 , resp . ; p while uric acid increased ( F = 12.53 , p of depressive symptoms at 6 months significantly predicted one-year reduction in u-8-oxodG ( β = 0.15 , p = 0.044 ) . Conclusion . Simple behavioral interventions are capable not only of alleviating depressive symptoms , but also of reducing the intensity of damaging oxidative/inflammatory processes in type 2 diabetic patients with subsyndromal depression . This trial is registered with IS RCT N05673017", "Hispanics are at increased risk of morbidity and mortality due to their high prevalence of diabetes and poor glycemic control . Strength training is the most effective lifestyle intervention to increase muscle mass but limited data is available in older adults with diabetes . We determined the influence of strength training on muscle quality ( strength per unit of muscle mass ) , skeletal muscle fiber hypertrophy , and metabolic control including insulin resistance ( Homeostasis Model Assessment –HOMA-IR ) , C-Reactive Protein ( CRP ) , adiponectin and Free Fatty Acid ( FFA ) levels in Hispanic older adults . Sixty-two community-dwelling Hispanics ( > 55 y ) with type 2 diabetes were r and omized to 16 weeks of strength training plus st and ard care ( ST group ) or st and ard care alone ( CON group ) . Skeletal muscle biopsies and biochemical measures were taken at baseline and 16 weeks . The ST group show improved muscle quality ( mean±SE : 28±3 ) vs CON ( -4±2 , p increased type I ( 860±252µm2 ) and type II fiber cross-sectional area ( 720±285µm2 ) compared to CON ( type I : -164±290µm2 , p=0.04 ; and type II : -130±336µm2 , p=0.04 ) . This was accompanied by reduced insulin resistance [ ST : median ( interquartile range ) -0.7(3.6 ) vs CON : 0.8(3.8 ) , p=0.05 ] ; FFA ( ST : -84±30µmol/L vs CON : 149±48µmol/L , p=0.02 ) ; and CRP [ ST : -1.3(2.9)mg/L vs CON : 0.4(2.3)mg/L , p=0.05 ] . Serum adiponectin increased with ST [ 1.0(1.8)µg/mL ] compared to CON [ -1.2(2.2)µg/mL , p ] . Strength training improved muscle quality and whole-body insulin sensitivity . Decreased inflammation and increased adiponectin levels were related with improved metabolic control . Further studies are needed to underst and the mechanisms associated with these findings . However , these data show that strength training is an exercise modality to consider as an adjunct of st and ard of care in high risk population s with type 2 diabetes", "OBJECTIVES This study assessed the effect of a 12-week sports-based exercise intervention on glucose regulation , anthropometry and inflammatory markers associated with the prevalence of type 2 diabetes mellitus ( T2DM ) in Indigenous Australian men . DESIGN Twenty-six inactive Indigenous Australian men ( 48.6±6.6 years ) were r and omized into exercise ( n=16 ) or control (n=10)conditions . METHODS Training included ∼2 - 3 days/week for 12 weeks of sports and gym exercises in a group environment , whilst control participants maintained normal activity and dietary patterns . Pre- and post-intervention testing included : anthropometry , peak aerobic capacity , fasting blood chemistry of inflammatory cytokines , adiponectin , leptin , cholesterol , glucose , insulin and C-peptide . An oral glucose tolerance test measured glucose , insulin and C-peptide 30 , 60 , 90 and 120min post 75 g glucose ingestion . RESULTS The exercise condition decreased insulin area under the curve ( 25±22 % ) , increased estimated insulin sensitivity ( 35±62 % ) and decreased insulin resistance ( 9±35 % ; p0.05 ) . The exercise condition decreased in body mass index , waist circumference and waist to hip ratio ( p0.05 ) . Leptin decreased in the exercise group , with no changes for adiponectin ( p>0.05 ) or inflammatory markers ( p>0.05 ) in either condition . Aerobic fitness variables showed significant increases in peak oxygen consumption for the exercise condition compared to no change in control ( p>0.05 ) . CONCLUSIONS Findings indicate positive clinical outcomes in metabolic , anthropometric and aerobic fitness variables . This study provides evidence for sport and group-based activities leading to improved clinical risk factors associated with T2DM development in clinical ly obese Indigenous Australian men", "AIM The effects of exercise intervention and to assess its long-term efficacy in preventing subsequent cardiovascular events in patients with type 2 diabetes were little known on r and omized controlled trial . METHODS Thirty-eight type 2 diabetic patients ( 21 men and 17 women ) were assigned to either the exercise group ( n=21 ) or the control group without exercise training ( n=17 ) by simple r and omization . The exercise training group was scheduled for aerobic and resistance exercise programs for 3 months . After the 3-month , we investigated endothelial function , insulin resistance , adipocytokines and inflammatory markers . The endothelial function was evaluated by examining a flow-mediated endothelium-dependent vasodilatation ( FMD ) . Furthermore , we followed the incidence of cardiovascular events for 24 months . RESULTS After 3-month , HbA1C was decreased significantly in both groups . FMD was increased from 7.3+/-4.7 % to 10.9+/-6.2 % only in the exercise group ( p cardiovascular events more frequently than did the exercise group ( p Exercise improves endothelial dysfunction independently of glycemic control and insulin sensitivity in patients with type 2 diabetes . The beneficial effects of 3-month exercise to reduce cardiovascular events persist for 24 months", "BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin", "The purpose of this study was to determine the effect of exercise training on the levels of C-reactive protein ( CRP ) and adiponectin , and to assess whether exercise-induced changes in insulin resistance could be explained in part by changes in these inflammation markers . Study participants included 51 middle-aged ( 45.3+/-8.3 years ; mean+/-SD ) , overweight ( 33.7+/-4.8 BMI ) , insulin-resistant , nondiabetic individuals . Subjects had their insulin sensitivity , body fat , CRP , and adiponectin levels measured , and their predicted maximal fitness calculated before and after 16 weeks of moderate , intense , or no exercise training . Modest improvements in fitness , body composition , and insulin sensitivity were observed , but these changes were not associated with decreased CRP or increased adiponectin levels , even when subjects were stratified by their change in fitness or obesity . Regression analysis demonstrated that the change in percentage of body fat was significantly related to changes in insulin sensitivity , whereas changes in VO2 MAX , CRP , and adiponectin were not . Participation in moderate to intense exercise was not associated with improved measures of chronic inflammation markers , as measured by CRP and adiponectin . Moreover , improvements in insulin sensitivity result ing from exercise or modest weight loss did not appear to be related to changes in these markers", "Aims /hypothesisAdipokines may be important in mediating signals from adipocytes to insulin-sensitive tissue and vasculature . We studied the effect of different glucose-lowering therapies on serum levels of plasminogen activator inhibitor-1 ( PAI-1 ) , high-sensitivity C-reactive protein ( hs-CRP ) , TNF-α , leptin , adiponectin and ghrelin in patients with type 2 diabetes . Subjects and methods Twenty-eight patients with poorly controlled type 2 diabetes who were receiving oral hypoglycaemic agents were allocated to one of the following groups , and treated for 1 year : ( 1 ) lifestyle intervention ( L ) ; ( 2 ) insulin treatment ( I ) ; and ( 3 ) combined treatment ( L+I ) . Results Similar improvements in glycaemic control occurred in all three groups . There was a reduction in body weight of 3.0 kg ( median ) ( 95 % CI −5.9 to −2.0 ) in group L , whereas in groups L+I and I body weight increased by 3.5 kg ( 95 % CI 1.5–4.9 ) and 4.9 kg ( 95 % CI −3.1 to 8.2 ) , respectively . By trend analyses , group L had reduced levels of PAI-1 ( p=0.002 ) , hs-CRP ( p the levels of leptin or adiponectin . In group I , the median levels of PAI-1 ( p=0.008 ) , TNF-α ( p=0.058 ) and leptin ( p=0.004 ) increased . In the L+I group there was a reduction in PAI-1 levels ( p=0.014 ) and an increase in levels of leptin ( p in the levels of PAI-1 , hs-CRP , TNF-α and leptin between groups were also significant ( all p lifestyle intervention in type 2 diabetes had more beneficial effects on adipokine levels than when the same lowering of HbA1c was achieved with insulin treatment", "For decades , exercise has been considered a cornerstone of diabetes management , along with diet and medication . However , high- quality evidence on the importance of exercise and fitness in diabetes was lacking until recent years . The present document summarizes the most clinical ly relevant recent advances related to people with type 2 diabetes and the recommendations that follow from these . Our recently published technical review on physical activity/exercise and type 2 diabetes ( 1 ) includes greater detail on individual studies , on prevention of diabetes , and on the physiology of exercise . The present statement focuses on type 2 diabetes . Issues primarily germane to type 1 diabetes will be covered in a subsequent technical review and ADA Statement . The levels of evidence used are defined by the ADA in ref . 2 . Two r and omized trials each found that lifestyle interventions including ∼150 min/week of physical activity and diet-induced weight loss of 5–7 % reduced the risk of progression from impaired glucose tolerance ( IGT ) to type 2 diabetes by 58 % ( 3,4 ) . A cluster-r and omized trial found that diet alone , exercise alone , and combined diet and exercise were equally effective in reducting the progression from IGT to diabetes ( 5 ) . Therefore , there is firm and consistent evidence that programs of increased physical activity and modest weight loss reduce the incidence of type 2 diabetes in individuals with IGT . Boule et al. ( 6 ) undertook a systematic review and meta- analysis on the effects of structured exercise interventions in clinical trials of ≥8 weeks duration on HbA1c ( A1C ) and body mass in people with type 2 diabetes . Postintervention A1C was significantly lower in exercise than control groups ( 7.65 vs. 8.31 % , weighted mean difference −0.66 % ; P contrast , postintervention body weight did not differ between the exercise and control groups . Meta-regression confirmed that the beneficial effect of exercise on A1C", "Background Diabetes mellitus ( DM ) and chronic inflammation are strongly related to increased cardiovascular risk . The purpose of this study was to evaluate whether an aerobic training programme would ameliorate inflammatory and anti-inflammatory markers in patients with type 2 DM . Design Interventional study . Methods A total of 60 overweight individuals with type 2 DM , but without vascular complications , were r and omly assigned to either a 6-month aerobic exercise training programme ( four times/week , 45 - 60 min/session ) , design ated as exercise group , or to the control group . All participants were on an oral antidiabetic regimen and none was receiving lipid-lowering medications . Anthropometric parameters , cardiorespiratory fitness , glycaemic and lipid profiles , high sensitivity C-reactive protein ( hs CRP ) , adiponectin , interleukin (IL)-10 , IL-18 , tumour necrosis factor (TNF)-a , insulin , reciprocal index of homoeostasis model assessment ( HOMA-IR ) , body fat and blood pressure ( BP ) were measured at baseline and at the end of the study . Results In comparison with baseline and control group , exercise-treated patients improved glucose control , lipid profile , exercise capacity ( Vo2 peak ) and exhibited decreased insulin resistance and systolic BP considerably ( P changed slightly across treatment ( P > 0.05 ) , whereas diastolic BP and fat mass tended to decrease ( P = 0.071 and 0.061 , respectively ) . Exercise training reduced hs CRP ( from 0.48 ± 0.16 to 0.29 ± 0.2 mg/dl ; P = 0.04 ) and IL-18 ( from 315.19 ± 122.76 to 203.77 ± 96.02 pg/ml ; P = 0.02 ) . Moreover , exercise provided anti-inflammatory protection through IL-10 increment ( P = 0.039 ) and IL-18/IL-10 ratio downregulation ( P = 0.014 ) . In multiple regression analysis , alteration in IL-18 was independently correlated with hs CRP and Vo2 peak changes ( P ) . Conclusion Aerobic exercise training without significant weight loss improves metabolic profile and exerts anti-inflammatory effects in patients with type 2 DM . Eur J Cardiovasc Prev Rehabil 14 : 837 - 843 © 2007 The European Society of", "Background : Dysregulation of adipokines , such as adiponectin and leptin , is associated with a variety of chronic diseases , including cancer . Physical activity protects against breast cancer and one of the mechanisms which may underlie this association is exercise-induced changes in adipokine levels . The WISER Sister Trial was a three-armed r and omized controlled trial in premenopausal women ( n = 137 ) with an elevated risk for breast cancer . Methods : A 5-menstrual-cycle-long dosed aerobic exercise intervention compared low-dose exercise ( 150 min/wk ; n = 44 ) or high-dose exercise ( 300 min/wk ; n = 48 ) with a control group asked to maintain usual activity levels ( n = 45 ) . Exercise intensity progressed to and was maintained at 70 % to 80 % of age predicted heart rate max . Body composition and adipokine levels were measured at baseline and follow-up . Results : We observed significant linear trends for increased fitness capacity ( Δ% : −2.0 % control , 10.1 % low dose , 13.1 % high dose ) , decreased fat tissue-to-total tissue mass ( Δ% : 0.7 % control , −2.9 % low dose , −3.7 % high dose ) , increased body fat adjusted adiponectin ( Δ% : −0.6 % control , 0.6 % low dose , 0.9 % high dose ) , and decreased body fat adjusted leptin ( Δ% : 0.7 % control , −8.2 % low dose , −10.2 % high dose ) . Conclusions : In this r and omized clinical trial of premenopausal women at risk for breast cancer , we demonstrate a dose – response effect of exercise on adiponectin and leptin and that dose response is dependent on changes in body fat . Impact : Improved adipokine levels , achieved by aerobic exercise training-induced decreases in body fat , may decrease breast cancer risk for high-risk premenopausal women . Cancer Epidemiol Biomarkers Prev ; 25(8 ) ; 1195–200 . © 2016 AACR", "OBJECTIVE We investigated the effect of an intensive training program on fasting leptin and adiponectin levels . METHODS Sixteen middle-aged men with type 2 diabetes were r and omly assigned to either a training or control group . The training program consisted of 8 weeks of supervised endurance exercise ( 75 % VO(2peak ) , 45 min ) twice a week , with intermittent exercise ( five 2 min exercises at 85 % VO(2peak ) separated by 3 min exercises at 50 % VO(2peak ) ) once a week , on an ergocycle . RESULTS Training decreased abdominal fat by 44 % , increased mid-thigh muscle cross-sectional area by 24 % , and improved insulin sensitivity by 58 % without significant change in body weight . Compared with controls , no significant variation in leptin or adiponectin levels was observed . However , in the trained group , change in adiponectin correlated with change in body weight ( Spearman rank correlation , r(s):-0.76 , P=0.03 ) but not with insulin sensitivity or abdominal adiposity variations . CONCLUSIONS An 8 week intensive training program inducing a marked reduction in abdominal fat and increase in insulin sensitivity does not affect adiponectin and leptin levels in men with type 2 diabetes", "Lipid accumulation in muscle is associated with diminished insulin sensitivity . It was hypothesized that resistance exercise decreases muscular adipose tissue and reduces the level of retinol-binding protein-4 ( RBP4 ) , which is linked to adipose tissue and insulin sensitivity in diabetics . Forty-four women with type 2 diabetes were r and omly assigned to three groups for a period of 12 weeks : control ( asked to maintain a sedentary lifestyle ) ; resistance exercise ( elastic b and exercise at moderate intensity five times per week ) ; and aerobic exercise ( walking for 60 min at moderate intensity five times per week ) . Subcutaneous ( SCAT ) , subfascial ( SFAT ) and intramuscular ( IMAT ) adipose tissues at mid-thigh level were assessed using computed tomography , and RBP4 level and insulin sensitivity ( fractional disappearance rate of insulin , k ITT ) were assessed before and after intervention . Changes in SCAT , SFAT , IMAT , RBP4 and k ITT were similar among the three groups . Within-group analysis revealed that body mass index and waist circumference decreased significantly in both exercise groups , but RBP4 decreased significantly only with resistance exercise . Resistance exercise did not alter muscular adipose tissue or improve insulin sensitivity", "BACKGROUND Excess body weight and a sedentary lifestyle are associated with the development of several diseases , including cardiovascular disease , diabetes and cancer in women . One proposed mechanism linking obesity to chronic diseases is an alteration in adipose-derived adiponectin and leptin levels . We investigated the effects of 12-month reduced calorie , weight loss and exercise interventions on adiponectin and leptin concentrations . METHODS Overweight/obese postmenopausal women ( n = 439 ) were r and omized as follows : ( i ) a reduced calorie , weight-loss diet ( diet ; N = 118 ) , ( ii ) moderate-to-vigorous intensity aerobic exercise ( exercise ; N = 117 ) , ( iii ) a combination of a reduced calorie , weight-loss diet and moderate-to-vigorous intensity aerobic exercise ( diet + exercise ; N = 117 ) , and ( iv ) control ( N = 87 ) . The reduced calorie diet had a 10 % weight-loss goal . The exercise intervention consisted of 45 min of moderate-to-vigorous aerobic activity 5 days per week . Adiponectin and leptin levels were measured at baseline and after 12 months of intervention using a radioimmunoassay . RESULTS Adiponectin increased by 9.5 % in the diet group and 6.6 % in the diet + exercise group ( both P ≤ 0.0001 vs. control ) . Compared with controls , leptin decreased with all interventions ( diet + exercise , -40.1 % , P diet , -27.1 % , P exercise , -12.7 % , P = 0.005 ) . The results were not influenced by the baseline body mass index ( BMI ) . The degree of weight loss was inversely associated with concentrations of adiponectin ( diet , P-trend = 0.0002 ; diet + exercise , P-trend = 0.0005 ) and directly associated with leptin ( diet , P-trend diet + exercise , P-trend through diet or diet + exercise increased adiponectin concentrations . Leptin concentrations decreased in all of the intervention groups , but the greatest reduction occurred with diet + exercise . Weight loss and exercise exerted some beneficial effects on chronic diseases via effects on adiponectin and leptin" ]	41189c6c-06ff-11f0-808a-c43d1ab1c353
ABSTRACT Interest is increasing regarding the potential health effects of red yeast rice ( RYR ) consumption , which is described as a “ natural statin ” in China . This review aims to evaluate the efficacy of RYR on blood pressure ( BP ) , lipid profile , and C-reactive protein ( CRP ) in treating hypertension . Seven electronic data bases including the Cochrane Central Register of Controlled Trials , EMBASE , PubMed , the Chinese National Knowledge Infrastructure ( CNKI ) , the Chinese Scientific Journal Data base ( VIP ) , the Chinese Biomedical Literature Data base ( CBM ) , and the Wanfang data base were search ed . To investigate the role of RYR for hypertension , r and omized controlled trials for the use of RYR either as monotherapy or in combination with conventional medicine versus placebo , no intervention , or conventional medicine for hypertension were identified . A total of 21 trials containing 4558 patients were analyzed , the majority of which had low method ological quality . “ RYR plus conventional therapy ” exhibited significant lowering effects on serum total cholesterol ( TC ) , low-density lipoprotein cholesterol ( LDL-C ) , and CRP but exhibited no significant effect on systolic BP , diastolic BP , triglycerides ( TG ) , and high-density lipoprotein cholesterol ( HDL-C ) compared with “ placebo plus conventional therapy . ” “ RYR plus conventional therapy ” showed significant lowering effects on systolic BP , TC , LDL-C , and CRP but no effect on diastolic BP , TG , and HDL-C compared with “ placebo plus conventional therapy . ” No significant difference in BP and lipid profile between “ RYR plus conventional therapy ” and “ statins plus conventional therapy ” was observed . “ RYR plus statins ” appeared to be more effective in lowering BP , TC , TG , and LDL-C but without a significant difference in HDL-C compared to statins . No serious adverse events were reported . The results of this meta- analysis suggested some supportive but limited evidence regarding RYR for hypertension . Further rigorously design ed trials are warranted before RYR could be recommended to hypertensive patients	[ "Abstract Background . The lowering of cholesterol concentrations in individuals at high risk for cardiovascular disease improves clinical outcome . Xuezhikang has a marked impact on lipids . Methods . In this r and omized , double-blinded , placebo-controlled , parallel-group clinical trial , a total of 2704 hypertensive patients with previous myocardial infa rct ion ( MI ) were assigned either to placebo ( n = 1341 ) or to Xuezhikang ( 0.6 g twice daily , n = 1363 ) for an average of 4.5 years . The primary end-point was recurrent coronary events ; the secondary end-point was all-cause mortality and other clinical events , including adverse effects . Results . There were no differences between the Xuezhikang and placebo group in base-line characteristics . However , Xuezhikang treatment reduced the incidence of coronary events by 43.0 % ( P = 0.02 ) , deaths from coronary heart disease ( CHD ) by 30.0 % ( P all-cause mortality by 35.8 % ( P = 0.001 ) . Conclusions . This study , for the first time , demonstrated that long-term Xuezhikang therapy result ed in significant reduction in cardiovascular events and death in Chinese hypertensive patients with previous MI in a safe manner", "Lipid-lowering therapy in individuals with high risk of cardiovascular disease reduces the incidence of coronary heart disease . However , few studies have assessed the benefits of cholesterol lowering for primary prevention of coronary heart disease in hypertensive patients with mild dyslipidemia or without conventional dyslipidemia . The large , r and omized Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese Study showed a 33 % reduction in coronary heart disease incidence with pravastatin as the primary prevention in Japanese patients . We conducted an exploratory analysis of the effect of diet plus pravastatin therapy on the primary prevention of cardiovascular events ( coronary heart disease , coronary heart disease plus cerebral infa rct ion , and cardiovascular disease ) in the 3277 patients with hypertension during the 5-year follow-up . There were no significant differences in mean baseline total cholesterol , blood pressure levels , or variation in blood pressure during the 5-year period between the diet ( n=1664 ) and diet plus pravastatin ( n=1613 ) groups . In the diet plus pravastatin group , the relative risk of coronary heart disease plus cerebral infa rct ion was reduced by 35 % ( hazard ratio : 0.65 ; CI : 0.46 to 0.93 ; P=0.02 ) , cerebral infa rct ion by 46 % ( hazard ratio : 0.54 ; CI : 0.29 to 0.98 ; P=0.04 ) , and cardiovascular disease by 33 % ( hazard ratio : 0.67 ; CI : 0.49 to 0.91 ; P=0.01 ) . In patients without a history of cardiovascular disease who have hypertension and mildly elevated cholesterol , pravastatin was effective in reducing the incidence of cardiovascular disease , particularly cerebral infa rct ion . Hence , in patients with hypertension with mildly elevated cholesterol levels , treatment with a statin is advisable to reduce the burden of cardiovascular disease", "Objective To observe the effect of combined therapy with Xuezhikang Capsule ( 血脂康胶囊 , XZK ) and Valsartan on left ventricular hypertrophy ( LVH ) and heart rate turbulence ( HRT ) in hypertensive patients . Methods Ninety primary hypertensive patients with LVH were r and omly assigned to three groups . Basic treatment , including aspirin , β-blockers , calcium antagonists , etc . were administered to all patients . Additionally , Valsartan ( VS , 80 mg once a day ) was given to the 30 patients in the VS group . Valsartan ( in the same dosage ) and XZK ( 600 mg , twice a day ) were given to the 32 patients in the Chinese medicine ( CM ) group , while none was given to the 28 patients in the control group . The therapeutic course lasted for 24 months . Changes in left ventricular mass index ( LVMI ) measured by cardiac ultrasonic indices , HRT parameters , including the original heart rate ( TO ) and slope coeffificient ( TS ) , systolic and diastolic blood pressures ( SBP and DBP ) , as well as blood cholesterol level ( TC ) were measured before and after treatment . Results After treatment , TO and LVMI were lowered , while TS increased in both the VS group and the CM group ( P in terms of TO , LVMI , SBP , DBP and TS ( P terms of TO , LVMI and TS ( P Moreover , HRT parameters showed an evident correlation with LVMI ( r=0.519–0.635 , P Combined therapy with XZK and Valsartan can improve hypertensive LVH and HRT parameters , and lessen the damage on the autonomous nervous system", "Summary Background The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome . No study , however , has assessed benefits of cholesterol lowering in the primary prevention of coronary heart disease ( CHD ) in hypertensive patients who are not conventionally deemed dyslipidaemic . Methods Of 19 342 hypertensive patients ( aged 40–79 years with at least three other cardiovascular risk factors ) r and omised to one of two antihypertensive regimens in the Anglo-Sc and inavian Cardiac Outcomes Trial , 10 305 with nonfasting total cholesterol concentrations 6.5 mmol/L or less were r and omly assigned additional atorvastatin 10 mg or placebo . These patients formed the lipid-lowering arm of the study . We planned follow-up for an average of 5 years , the primary endpoint being non-fatal myocardial infa rct ion and fatal CHD . Data were analysed by intention to treat . Findings Treatment was stopped after a median follow-up of 3.3 years . By that time , 100 primary events had occurred in the atorvastatin group compared with 154 events in the placebo group ( hazard ratio 0.64 [ 95 % CI 0.50–0.83 ] , p = 0.0005 ) . This benefit emerged in the first year of follow-up . There was no significant heterogeneity among prespecified subgroups . Fatal and non-fatal stroke ( 89 atorvastatin vs 121 placebo , 0.73 [ 0.56–0.96 ] , p = 0.024 ) , total cardiovascular events ( 389 vs 486 , 0.79 [ 0.69–0.90 ] , p = 0.0005 ) , and total coronary events ( 178 vs 247 , 0.71 [ 0.59–0.86 ] , p = 0.0005 ) were also significantly lowered . There were 185 deaths in the atorvastatin group and 212 in the placebo group ( 0.87 [ 0.71–1.06 ] , p = 0.16 ) . Atorvastatin lowered total serum cholesterol by about 1.3 mmol/L compared with placebo at 12 months , and by 1.1 mmol/L after 3 years of follow-up . Interpretation The reductions in major cardiovascular events with atorvastatin are large , given the short follow-up time . These findings may have implication s for future lipid-lowering guidelines", "BACKGROUND We examined the cholesterol-lowering effects of a proprietary Chinese red-yeast-rice supplement in an American population consuming a diet similar to the American Heart Association Step I diet using a double-blind , placebo-controlled , prospect ively r and omized 12-wk controlled trial at a university research center . OBJECTIVE We evaluated the lipid-lowering effects of this red-yeast-rice dietary supplement in US adults separate from effects of diet alone . DESIGN Eighty-three healthy subjects ( 46 men and 37 women aged 34 - 78 y ) with hyperlipidemia [ total cholesterol , 5.28 - 8.74 mmol/L ( 204 - 338 mg/dL ) ; LDL cholesterol , 3.31 - 7.16 mmol/L ( 128 - 277 mg/dL ) ; triacylglycerol , 0.62 - 2.78 mmol/L ( 55 - 246 mg/dL ) ; and HDL cholesterol 0.78 - 2.46 mmol/L ( 30 - 95 mg/dL ) ] who were not being treated with lipid-lowering drugs participated . Subjects were treated with red yeast rice ( 2.4 g/d ) or placebo and instructed to consume a diet providing 30 % of energy from fat , total cholesterol , total triacylglycerol , and HDL and LDL cholesterol measured at weeks 8 , 9 , 11 , and 12 . RESULTS Total cholesterol concentrations decreased significantly between baseline and 8 wk in the red-yeast-rice-treated group compared with the placebo-treated group [ ( x+/-SD ) 6.57+/-0.93 mmol/L ( 254+/-36 mg/dL ) to 5.38+/-0.80 mmol/L ( 208+/-31 mg/dL ) ; P LDL cholesterol and total triacylglycerol were also reduced with the supplement . HDL cholesterol did not change significantly . CONCLUSIONS Red yeast rice significantly reduces total cholesterol , LDL cholesterol , and total triacylglycerol concentrations compared with placebo and provides a new , novel , food-based approach to lowering cholesterol in the general population", "BACKGROUND Some studies have suggested reductions in blood pressure (BP)with statin treatment , particularly in persons with hypertension . R and omized trial evidence is limited . METHODS We performed a r and omized , double-blind , placebo-controlled trial with equal allocation to simvastatin , 20 mg ; pravastatin sodium,40 mg ; or placebo for 6 months . Nine hundred seventy-three men and women without known cardiovascular disease or diabetes mellitus , with low-density lipoprotein cholesterol screening levels of 115 to 190 mg/dL , had assessment of systolic and diastolic BP ( SBP and DBP , respectively ) . Blood pressure values were compared for placebo vs statins by intention-to-treat ( ITT ) analysis . Additional analyses were performed that ( 1 ) were confined to subjects with neither high baseline BP ( SBP>140 mm Hg or DBP>90 mm Hg ) nor receiving BP medications , to exclude groups in whom BP medications or medication changes may have influenced results , and ( 2 ) separately evaluated simvastatin and pravastatin ( vs placebo ) . The time course of BP changes after statin initiation and the effect of stopping statins on BP were examined . RESULTS Statins modestly but significantly reduced BP relative to placebo , by 2.2 mm Hg for SBP ( P=.02 ) and 2.4 mm Hg for DBP ( P Blood pressure reductions ranged from 2.4 to 2.8 mm Hg for both SBP and DBP with both simvastatin and pravastatin , in those subjects with full follow-up , and without potential for influence by BP medications ( ie , neither receiving nor meriting BP medications ) . CONCLUSIONS Reductions in SBP and DBP occurred with hydrophilic and lipophilic statins and extended to normotensive subjects . These modest effects may contribute to the reduced risk of stroke and cardiovascular events reported on statins . Trial Registration clinical trials.gov Identifier : NCT00330980", "BACKGROUND AND AIM Some clinical evidence supports a statin antihypertensive effect . Our aim is to evaluate the statin effect on blood pressure control in hypertensive patients in the setting of clinical practice , and the role of some predetermined individual patient characteristics ( age , gender , baseline BP levels , pre-treatment LDL-C levels ) on the supposed statin BP lowering effect . METHODS AND RESULTS Two hundred and fifty-four hypertensive patients with hypercholesterolemia were enrolled in the Ambulatory service of the Hypertension Research Unit of Bologna University Hospital . After 2 - 4 weeks of a run-in period patients were allocated to statin treatment and followed-up for 24 weeks . The blood pressure response to statins was compared in several subgroups of patients according to age , gender , baseline BP and pre-treatment cholesterolemia . In the overall study population , the use of statins was associated with a significant reduction in systolic ( -7.6+/-4 mmHg , p and diastolic blood pressures ( -5.2+/-3 mmHg , p blood pressure decrease was more pronounced in patients younger than 65 years ( p systolic blood pressure ( p statins ( p BP-lowering effect of statins , consistent with some other literature . Some parameters like age , baseline systolic blood pressure and cholesterolemia influence the antihypertensive effect of statins . The lack of consideration for these confounding factors may be one of the reasons for the conflicting results about the BP lowering effects of statins ", "AIM Patients with resistant hypertension are at high risk for adverse cardiovascular events . Efforts have been focused on lowering the surrogate endpoint of blood pressure ( BP ) with scant focus on reduction of hard cardiovascular endpoints . However , whether or not intensive lipid lowering is beneficial for reducing the risk of cardiovascular events in this high-risk cohort is not known . METHODS AND RESULTS We evaluated 10 001 patients with coronary artery disease and a low-density lipoprotein cholesterol level atorvastatin 80 vs. 10 mg , enrolled in the Treating to New Targets trial . Treatment-resistant hypertension ( TRH ) was defined as BP ≥140 mmHg despite being on three antihypertensive agents or 140 mmHg on four or more agents . Subjects were followed up for a median duration of 4.9 years . The primary outcome was major cardiovascular events ( composite of non-fatal myocardial infa rct ion ( MI ) , fatal coronary heart disease ( CHD ) , resuscitated cardiac arrest , and stroke ) . Among the 10 001 patients in the trial , 1112 ( 11.1 % ) patients had TRH . Atorvastatin 80 mg , in patients with TRH , was associated with a significant reduction in the risk of the primary outcome ( HR = 0.70 ; 95 % CI 0.52 - 0.93 ; P = 0.01 ) , driven largely by a significant reduction in CHD deaths ( HR = 0.55 ; 95 % CI 0.32 - 0.97 ; P = 0.04 ) . In addition , atorvastatin 80 mg was associated with a reduction in major coronary events ( HR = 0.67 ; 95 % CI 0.49 - 0.93 ; P = 0.02 ) , and any cardiovascular or coronary event and with a trend ( P = 0.05 ) towards reduction in all-cause mortality ( HR = 0.68 ; 95 % CI 0.46 - 1.01 ) when compared with atorvastatin 10 mg . The results were similar when analysed for the two separate components of the TRH cohort . CONCLUSION In subjects with TRH , intensive lipid lowering with atorvastatin 80 mg is associated with a significant reduction in cardiovascular events ", "OBJECTIVE To investigate whether statins have effect on diastolic function of both left and right ventricles in hypertensive patients . METHODS This is a r and omized , mono-blind , placebo-controlled study . 120 systemic hypertensive ( HT ) patients with normal or slightly elevated cholesterol were r and omized to placebo or Xuezhikang ( 1200 mg/d ) for 24 weeks . Extended-release nifedipine was administrated to the HT patients . 30 healthy volunteers served as controls . Plasma were obtained at baseline and 24 weeks after Xuezhikang therapy . Cholesterol and carboxy-terminal peptide of procollagen type I ( PIP ) were measured . Early diastolic velocity ( Em ) and late diastolic velocity ( Am ) were obtained from right atrioventricular ring and left atrioventricular ring with pulsed wave tissue Doppler imaging . RESULTS The levels of plasma PIP were higher in HT patients . After 24 weeks , the levels of plasma LDL-C , TC and PIP were significantly lower in Xuezhikang group than those in placebo group ; Systolic and diastolic pressure were decreased both in placebo group and Xuezhikang group meanwhile pulse pressure was decreased and Em/Am ratio at left atrioventricular ring was higher in Xuezhikang group as compared with those in placebo group . CONCLUSION In systemic hypertensive patients , Xuezhikang exerts a beneficial effect on diastolic function of left ventricule via controlling blood pressure , lowering blood lipid and inhibiting myocardial fibrosis", "Background —Endothelial dysfunction is associated with inflammation and postpr and ial hypertriglyceridemia . Xuezhikang , an extract of Cholestin , a dietary supplement , has lipid-modulating and antiinflammatory effects . We explored the effects of xuezhikang on endothelial function and high-sensitivity C-reactive protein ( hs-CRP ) in patients with coronary heart disease ( CHD ) . Methods and Results —We prospect ively r and omized 50 CHD patients to xuezhikang 1200 mg/d or placebo for 6 weeks . Fasting hs-CRP concentrations , flow-mediated vasodilation ( FMD ) at 0 and 4 hours , and lipid parameters at 0 , 2 , 4 , and 6 hours were monitored after a high-fat meal ( 800 calories ; 50 g fat ) in all patients . All patients underwent a high-fat meal test at the beginning of the study and after 6 weeks of treatment . Postpr and ial FMD was significantly worse at 4 hours after a high-fat meal ( P the triglyceride curve ( TG-AUC ) ( r=0.345 , P xuezhikang , fasting hs-CRP levels and TG-AUC ( P prepr and ial and postpr and ial FMD significantly improved ( P serum lipids and FMD in the placebo arm . In multivariable regression analysis , changes in TG-AUC and fasting hs-CRP levels were predictive of improvement in prepr and ial FMD ( P endothelial function through its potent antiinflammatory and lipid-lowering effects", "BACKGROUND Increased serum lipoprotein(a ) [ Lp(a ) ] and high-sensitivity C-reactive protein ( hsCRP ) concentrations are independent risk factors for coronary heart disease ( CHD ) . Xuezhikang , an extract of cholestin , effectively lowers fasting cholesterol and triglyceride concentrations . We studied whether xuezhikang lowered Lp(a ) and hsCRP concentrations . METHODS We r and omly divided 60 CHD patients into two groups to receive xuezhikang ( 1200 mg daily ) or placebo for 6 weeks . The fasting hsCRP concentration and the postpr and ial changes of serum lipid concentrations at 2 , 4 , and 6 h after a high-fat meal ( 800 calories ; 50 g of fat ) were measured before and after the 6-week protocol . RESULTS The two groups had similar baseline fasting lipid and hsCRP concentrations . The postpr and ial triglyceride and Lp(a ) concentrations were significantly increased ( P fasting and postpr and ial lipid concentrations decreased significantly in the xuezhikang group , accompanied by a significant reduction in fasting hsCRP concentration ( P lipid concentrations , whereas the fasting serum hsCRP concentration was reduced significantly ( P hsCRP was closely related to the changes in fasting Lp(a ) concentration ( r = 0.402 ; P Xuezhikang effectively decreased fasting Lp(a ) and postpr and ial triglyceride concentrations , which were associated with reductions of fasting hsCRP concentrations in CHD patients", "Background In recent years , red yeast rice ( RYR ) supplements have been marketed aggressively as a natural way to lower cholesterol ; however , the large majority of commercially available products have not been studied according to current research st and ards . Methods In a double blind placebo controlled r and omized trial , 52 physicians and their spouses with a total cholesterol level of > 200 mg/dL were r and omly allocated to receive a RYR extract or placebo for 8 weeks . As a primary outcome measure , we compared the before-after difference in lipid levels between both groups . As secondary outcome measures we looked at side-effects , CK elevation and a change in cardiovascular risk . Results LDL ( low density lipoprotein ) cholesterol was lowered with 36 mg/dL ( 22 % ) and total cholesterol with 37 mg/dL ( 15 % ) in the intervention group . This result was statistically significant as compared to the control group , in which no reduction in total cholesterol and LDL was observed ( p CK ( creatine kinase)-elevation or reported side-effects between study groups . In 5/31 participants in the intervention group , the lipid lowering effect result ed in lower cardiovascular risk as measured with SCORE ( Systematic COronary Risk Evaluation ) . Conclusions The RYR formulation under study was effective in lowering cholesterol and LDL cholesterol in this study population . RYR therapy may be an attractive and relatively well studied alternative in patients who are intolerant for statins or who have objections against pharmacological lipid lowering . However , consumers need to be warned that the actual content of commercially available preparations is not assured by governmental regulations , which raises effectiveness and safety issues . Trial registration Clinical trials.gov , nr :", "Objective To investigate the possibility that statins reduce blood pressure as well as cholesterol concentrations through clinic and 24 hour ambulatory blood pressure monitoring . Design R and omised placebo controlled double blind trial . Setting 13 hospitals in Italy Participants 508 patients with mild hypertension and hypercholesterolaemia , aged 45 to 70 years . Intervention Participants were r and omised to antihypertensive treatment ( hydrochlorothiazide 25 mg once daily or fosinopril 20 mg once daily ) with or without the addition of a statin ( pravastatin 40 mg once daily ) . Main outcome measures Clinic and ambulatory blood pressure measured every year throughout an average 2.6 year treatment period . Results Both the group receiving antihypertensive treatment without pravastatin ( n=254 ) ( with little change in total cholesterol ) and the group receiving antihypertensive treatment with pravastatin ( n=253 ) ( with marked and sustained reduction in total cholesterol and low density lipoprotein cholesterol ) had a clear cut sustained reduction in clinic measured systolic and diastolic blood pressure as well as in 24 hour , and day and night , systolic and diastolic blood pressure . Pravastatin performed slightly worse than placebo , and between group differences did not exceed 1.9 ( 95 % confidence interval −0.6 to 4.3 , P=0.13 ) mm Hg throughout the treatment period . This was also the case when participants who remained on monotherapy with hydrochlorothiazide or fosinopril throughout the study were considered separately . Conclusions Administration of a statin in hypertensive patients in whom blood pressure is effectively reduced by concomitant antihypertensive treatment does not have an additional blood pressure lowering effect . Trial registration BRISQUI_*IV_2004_001 ( registered at Osservatorio Nazionale sulla Sperimentazione Clinica dei Medicinali — National Monitoring Centre on Clinical Research with Medicines )", "Objective . The aim of this overview was to summarize the outcome measures of Chinese herbal medicine ( CHM ) for the treatment of hypertension based on available systematic review s ( SRs ) , so as to evaluate the potential benefits and advantages of CHM on hypertension . Methods . Literature search es were conducted in the Cochrane Data base of Systematic Review s , MEDLINE , and 4 data bases in Chinese . SRs of CHM for hypertension were included . Two independent review ers ( J. Wang and X. J. Xiong ) extracted the data . Results . 10 SRs were included . 2 SRs had primary endpoints , while others focused on secondary endpoints to evaluate CHM for hypertension such as blood pressure ( BP ) and Traditional Chinese Medicine ( TCM ) syndrome . 6 SRs have reported the adverse effects , whereas the other 4 SRs have not mentioned it at all . Many CHM appeared to have significant effect on improving BP , TCM syndrome , and so on . However , most SRs failed to make a definite conclusion for the effectiveness of CHM for hypertension due to poor evidence . Conclusion . Primary endpoints have not been widely used currently . The benefits of CHM for hypertension need to be confirmed in the future with r and omized controlled trials ( RCTs ) of more persuasive primary endpoints and high- quality SRs", "The effect of xuezhikang on postpr and ial triglyceride ( TG ) level was investigated in patients with coronary heart disease ( CHD ) after a high-fat meal ( 800 cal ; 50 g fat ) . Fifty CHD patients were r and omly divided into two groups to accept xuezhikang ( xuezhikang group ) 1200 mg/day ( 600 mg twice daily ) or not ( control group ) on the base of routine therapy which included aspirin , metoprolol and fosinopril and nitrates during the whole 6 weeks following-up . Xuezhikang significantly reduced fasting serum total cholesterol ( TC ) ( -20 % ) , low-density lipoprotein cholesterol ( LDL-C , -34 % ) , TG ( -32 % ) and apoB ( -27 % ) levels , and raised fasting high-density lipoprotein cholesterol ( HDL-C , 18 % ) and apoA-I ( 13 % ) levels ( P postpr and ial serum TG levels at 2 , 4 and 6 h decreased 32 , 38 and 43 % , respectively , in xuezhikang group ( P TG area under the curve over the fasting TG level ( TG-AUC ) significantly decreased in CHD patients accepted xuezhikang with normal ( less than 1.7 mmol/l ) and elevated ( 1.74 to 2.92 mmol/l ) fasting TG levels by 45 and 50 % , respectively ( P fasting and postpr and ial lipid and apolipoprotein levels . The change of TG-AUC was significantly related to the changes of fasting TG , TC , LDL-C , and HDL-C levels after the treatment , which were related to the changes of fasting apoA-I and apoB levels significantly ( P Xuezhikang was shown to be beneficial in the treatment of reflecting postpr and ial triglyceridemia in CHD patients with normal and mildly elevated fasting TG levels", "BACKGROUND Previous studies have suggested that the lipid-lowering agents , statins , may help reduce blood pressure ( BP ) . The goal of the present study was to characterize the effect of pravastatin on BP in hypercholesterolemic and hypertensive patients already receiving antihypertensive drugs . METHODS AND RESULTS Eighty-two patients with hypercholesterolemia were retrospectively studied before and after 3 months of treatment with pravastatin . Forty-four patients had hypertension ( HT group ) and were receiving antihypertensive treatment , while the remaining 38 patients were normotensive ( NT group ) . Patients in the HT group were further subdivided into those with uncontrolled or controlled BP . Pravastatin treatment significantly reduced systolic BP ( SBP ) in the HT group ( 134+/-16 to 130+/-13 mmHg , p low-density lipoprotein cholesterol in both groups ( HT group 178+/-27 to 132+/-17 mg/dl , p pravastatin significantly decreased SBP in the uncontrolled BP group ( 148+/-7 to 138+/-12 mmHg , p statins and antihypertensive drugs could result in improved BP control in hypertensive patients with hypercholesterolemia", "OBJECTIVES To evaluate whether lipid-lowering therapy with xuezhikang reduces the risk of coronary events and total mortality in patients with coronary heart disease ( CHD ) aged 65 and older . DESIGN Subgroup analysis of the China Coronary Secondary Prevention Study , a r and omized , double-blind , placebo-controlled , clinical trial . SETTING Sixty-six hospitals in China . PARTICIPANTS A total of 1,445 patients , aged 65 to 75 , were chosen from 4,780 patients with a history of myocardial infa rct ion . INTERVENTION The patients were r and omized to the xuezhikang ( n=735 ) or the placebo ( n=710 ) group and followed for a mean of 4 years . MEASUREMENTS The primary endpoint was recurrent coronary events ; the secondary endpoint was all-cause mortality and other clinical events , including adverse effects . RESULTS Elderly patients were at greater risk for coronary events , death from coronary events , all-cause mortality , and malignancies than younger patients . Xuezhikang therapy reduced the incidence of coronary events 36.9 % ( P=.001 ) , death from coronary heart disease 31.0 % ( P=.04 ) , all-cause mortality 31.9 % ( P=.01 ) , stroke 44.1 % ( P=.04 ) , the need for a percutaneous coronary intervention or coronary artery bypass graft 48.6 % ( P=.07 ) , and malignancies 51.4 % ( P=.03 ) . Based on the treatment of elderly patients with xuezhikang for an average of 4 years , the number needed to treat ( NNT ) to prevent one coronary event , one coronary death , and one mortality due to all causes was estimated to be 18 , 33 , and 23 , respectively . In a like manner , the estimated NNT to prevent one coronary event , one coronary death , and one mortality due to all causes in younger patients was 23 , 82 , and 51 , respectively . There was not a significantly greater number of adverse effects in the xuezhikang group than in the placebo group . CONCLUSION This is the first study demonstrating that treatment with xuezhikang capsules is safe and effective for the secondary prevention of CHD in older Chinese people", "Several previous trials from Western population studies have showed that statins may help reduce blood pressure ( BP ) . However , r and omized clinical data is limited . Xuezhikang , a partially extract of red yeast rice , contains a family of naturally occurring statins , and has a marked impact on lipids , but it is unknown whether Xuezhikang has any effect on BP during long-term follow-up in the Chinese population . This is a post-hoc subgroup analysis of a r and omized , double-blinded , placebo-controlled , parallel group clinical trial , Chinese Coronary Secondary Prevention Study ( CCSPS ) . A total of 2704 hypertensive patients with previous myocardial infa rct ion ( MI ) were assigned either to placebo ( n = = 1341 ) or to Xuezhikang ( n = = 1363 ) daily for an average of 4.5 years . The primary outcome was the unadjusted changes in mean arterial pressure ( MAP ) from baseline to 6 months . We also assessed systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , and pulse pressure . Analysis of covariance was used to calculate the adjusted effects of treatment on changes in these outcomes at 6 , 12 , 24 , and 48 months post-r and om- ization , after controlling for potential confounders . This analysis included 2704//4870 ( 55.5%% ) hypertensive patients for whom BP was measured at baseline and at least one follow-up visit after r and omization . Median duration of the follow-up was 4.5 years ( 54 months ) , and 25 patients ( 0.92%% ) were lost to the last follow-up because of adverse effects . The results showed that the unadjusted and adjusted changes in MAP , SBP , DBP , or pulse pressure from baseline were not significantly different for Xuezhikang or placebo recipients at 6 , 12 , 24 , and 48 months after r and omization . In this post-hoc subgroup analysis , we failed to demonstrate any significant reducing effects of Xuezhikang on BP in Chinese hypertensive patients with previous MI , suggesting that further prospect i ve study on the effects of statins on BP would be needed , especially in high-risk patients", "Coronary heart disease , hypertension , and dyslipidemia are highly prevalent and commonly coexist in people who are middle-aged and older . Previous data suggested that lowering cholesterol concentrations in individuals at high risk of cardiovascular disease improved clinical outcomes . Xuezhikang , a partial extract of red yeast rice containing statin , has a marked impact on lipids . The purpose of this study , therefore , was to evaluate the impact of Xuezhikang on reducing cardiovascular events and mortality in elderly Chinese hypertensive patients with a history of myocardial infa rct ion ( MI ) enrolled in the Chinese Coronary Secondary Prevention Study . In this r and omized trial , 1530 elderly hypertensive patients ( > or = 65-years-old ) with previous MI were assigned either to placebo ( n = 758 ) or to Xuezhikang ( n = 772 ) daily for an average of 4.5 years . The primary endpoint was recurrent coronary events ; the secondary endpoint was all-cause mortality and other clinical events , including adverse effects . There were 68 cases of coronary events ( 8.8 % ) detected in the Xuezhikang group and 108 cases ( 14.3 % ) in the placebo group ( 38.2 % risk reduction by Xuezhikang therapy ) . Death from coronary heart disease ( CHD ) totaled 49 cases in the Xuezhikang group ( 6.4 % ) and 68 cases in the placebo group ( 9.0 % ) , indicating that Xuezhikang significantly decreased the risk of CHD death by 29.2 % . Our study demonstrated that Xuezhikang therapy could effectively and safely reduce cardiovascular events and all-cause death in Chinese elderly hypertensive patients with previous MI . This finding may have an important implication for the treatment of elderly hypertensive patients with CHD", "Objective To investigate the impacts of Xuezhikang ( 血脂康 , XZK ) or pravastatin combined with antihypertensive drugs on circulating endothelial progenitor cells ( CEPCs ) in essential hypertensive ( EH ) patients . Methods Eighty-eight EH patients were enrolled into the study and r and omly assigned to the antihypertensive drug treatment group ( ATH group , 29 cases ) , the pravastatin treatment group ( PRA group , 29 cases ) and the Xuezhikang treatment group ( XZK group , 30 cases ) . Patients in the 3 groups were treated with routine antihypertensive drugs . In addition , pravastatin and Xuezhikang were given to the patients in the PRA group and XZK group , respectively . After an eight-week treatment , CEPCs were counted using a laser scanning confocal microscope , and their proliferation function was evaluated by the MTT colorimetric assay and the adherent cell number was counted to estimate the adhesion function . Results After the treatment , CEPCs in the PRA group ( 116.60±5.70 ) and XZK group ( 114.40±6.55 ) was significantly higher than that in the ATH group ( 88.00±6.32 , P in the PRA group ( 0.406±0.016 , 33.60±4.26 ) and XZK group ( 0.415±0.018 , 34.30±3.77 ) were obviously superior to those in the ATH group ( 0.333±0.021 , P of XZK or pravastatin with the anti-hypertensive therapy could increase the CEPCs number and improve their function in EH patients with the blood pressure controlled by antihypertensive drugs , leading to benefits independent of pressure-lowering effects", "Lipid-lowering therapy has been proven to reduce macrovascular complications of type 2 diabetes . Xuezhikang is an extract of cholestin and has a markedly modulating effect on lipids , but the effect of xuezhikang on reducing coronary events in diabetic patients with coronary heart disease ( CHD ) is less clear . A total of 591 diabetic patients with CHD were r and omized to the xuezhikang group ( n = 306 ) and the placebo group ( n = 285 ) . During the average 4 years of follow-up , there were 28 cases of CHD events ( 9.2 % ) in the xuezhikang group and 53 cases ( 18.6 % ) in the placebo group . Risk reduction for CHD events was 50.8 % ( P xuezhikang treatment . Xuezhikang decreased the risk of non-fatal MI by 63.8 % , fatal MI by 58.5 % , CHD sudden death by 26.9 % , and other CHD death by 53.4 % . CHD death totaled to 21 cases in the xuezhikang group ( 6.9 % ) and 35 cases in the placebo group ( 12.3 % ) , indicating that xuezhikang significantly decreased the risk of CHD death by 44.1 % ( P died from various causes , among which there were 27 patients in the xuezhikang group and 45 patients in the placebo group . The risk for all-cause death was 44.1 % lower in the xuezhikang group than in the placebo group ( P xuezhikang therapy can be effective on reduction of cardiovascular events in diabetic patients with CHD with a reliable safety", "OBJECTIVE To investigate the benefits of long-term therapy with Xuezhikang , a cholestin extract , in combination with calcium channel blockers for improvement of left ventricular ( LV ) hypertrophy and function in patients with essential hypertension , as determined using echocardiography . DESIGN Fifty-five ( 55 ) hypertensive patients with normal blood low-density lipoprotein cholesterol ( LDL-C ) levels were r and omly assigned to the Xuezhikang group ( n = 28 , 1200 mg/d of Xuezhikang ) or the placebo group ( n = 27 , matched placebo ) . All of the patients were treated with extended-release nifedipine ( 20 mg twice daily ) . Thirty ( 30 ) normotensive subjects , matched for age and gender , were selected as a control group . Conventional echocardiography and tissue Doppler imaging were used to measure the left ventricle ( LV ) wall thickness and LV diastolic function at weeks 0 , 24 , and 72 during the period of observation . The serum levels of lipids , carboxy-terminal propeptide of procollagen type I ( PIP ) , and C-reactive protein ( CRP ) were determined as well . RESULTS The hypertensive patients had significantly elevated PIP and CRP levels in serum , increased LV wall thickness , and impaired LV diastolic function compared with the normotensive subjects ( 0.01 transmitral flow velocities ( E/A ratio ) ( 1.11 + /- 0.36 versus 0.85 + /- 0.24 , p myocardial motion velocities ( Em/Am ratio ) at the septal mitral annulus ( 0.90 + /- 0.19 versus 0.70 + /- 0.18 , p lateral mitral annulus ( 1.06 + /- 0.20 versus 0.86 + /- 0.14 , p LV wall thickness after 72 weeks of therapy with Xuezhikang . The serum levels of PIP ( 0.43 + /- 0.13 ng/mL versus 0.51 + /- 0.20 ng/mL , p CRP ( 0.32 + /- 0.13 mg/L versus 0.40 + /-0.17 mg/L , p LV diastolic function and blood pressure or lipid profile with Xuezhikang therapy . CONCLUSION Long-term therapy with Xuezhikang improved LV diastolic function , probably mediated through antifibrotic and anti-inflammatory effects and independent of blood pressure and lipid profiles in patients with essential hypertension", "BACKGROUND Small studies have suggested that lipid-lowering strategies , and particularly statins , could influence blood pressure ( BP ) control . The aim of the present study was to evaluate the effect of different lipid-lowering strategies on BP control of subjects with hypercholesterolemia who were enrolled in the prospect i ve , population -based , longitudinal Brisighella Heart Study . METHODS A total of 1356 subjects with total cholesterol levels > or=239 mg/dL were r and omly treated for 5 years ( 1988 - 1993 ) with 1 of these lipid-lowering regimens : low-fat diet , cholestyramine , gemfibrozil , or simvastatin . Participants were divided at baseline into 4 quartiles according to systolic BP level and examined for the percent change in systolic and diastolic BP during the 5 years of treatment . RESULTS A significant decrease in BP was observed in the 2 upper quartiles of systolic BP ( > or=140 mm Hg ) and was greater in subjects treated with cholesterol-lowering drugs who also had a greater reduction in plasma levels of low-density lipoprotein cholesterol . The BP decrease was greater in patients treated with statin drugs and , among those treated with antihypertensive drugs , in subjects in the fourth quartile . CONCLUSION The use of lipid-lowering measures could significantly improve BP control in subjects with both hypercholesterolemia and hypertension . The reduction in BP seems to be enhanced in subjects treated with statins", "BACKGROUND Statins have been reported to have direct vascular effects independent of cholesterol reduction . To assess the antihypertensive effect of statins , a crossover study was design ed to compare the depressor effect of pravastatin and probucol in hypertensive patients undergoing long-term treatment with antihypertensive drugs . METHODS The subjects enrolled in this study were 52 hypertensive patients ( 22 men and 30 women , mean age 62.8 + /- 9.3 years ) who were treated with the same antihypertensive drugs for more than 1 year and had serum cholesterol levels of more than 5.69 mmol/L. In 26 subjects , pravastatin at a dose of 10 mg/d was given first for 6 months followed by treatment with probucol at a dose of 500 mg/d , and vice versa in the remaining 26 subjects . Serum lipids , apolipoproteins , glucose , and insulin were measured on the final day of the control period , and pravastatin and probucol treatments . The homeostatic model assessment insulin resistance index ( HOMA-IR ) was used to assess insulin resistance . RESULTS The blood pressure decreased after pravastatin treatment ( 141.2 + /- 4.7/81.3 + /- 4.9 to 136.5 + /- 5.3/80.6 + /- 5.1 mm Hg , P Total cholesterol decreased significantly after pravastatin ( 6.69 + /- 0.69 to 5.23 + /- 0.77 mmol/L , P HOMA-IR was decreased by probucol ( 1.92 + /- 0.78 to 1.57 + /- 0.59 , P = .029 ) , whereas pravastatin had no effect on HOMA-IR . CONCLUSIONS It can be concluded that the depressor effect of pravastatin may have an additional benefit in the treatment of hypertensive patients with hyperlipidemia without any adverse effect on insulin sensitivity", "CONTEXT Although it has been hypothesized that hypertension is in part an inflammatory disorder , clinical data linking inflammation with incident hypertension are scarce . OBJECTIVE To examine whether C-reactive protein levels , a marker of systemic inflammation , are associated with incident hypertension . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve cohort study that began in 1992 of 20 525 female US health professionals aged 45 years or older who provided baseline blood sample s with initially normal levels of blood pressure ( BP ) ( systolic BP history of hypertension or antihypertensive medications ) and then followed up for a median of 7.8 years for the development of incident hypertension . Plasma C-reactive protein levels were measured and baseline coronary risk factors were collected . MAIN OUTCOME MEASURE Incident hypertension , defined as either a new physician diagnosis , the initiation of antihypertensive treatment , or self-reported systolic BP of at least 140 mm Hg or a diastolic BP of at least 90 mm Hg . RESULTS During follow-up , 5365 women developed incident hypertension . In crude models , the relative risks ( RRs ) and 95 % confidence intervals ( CIs ) of developing hypertension from the lowest ( referent ) to the highest levels of baseline C-reactive protein were 1.00 , 1.25 ( 95 % CI , 1.14 - 1.40 ) , 1.51 ( 95 % CI , 1.35 - 1.68 ) , 1.90 ( 95 % CI , 1.72 - 2.11 ) , and 2.50 ( 95 % CI , 2.27 - 2.75 ) ( linear trend P C-reactive protein was significantly associated with an increased risk of developing hypertension in all prespecified subgroups evaluated , including those with very low levels of baseline BP , as well as those with no traditional coronary risk factors . Similar results were found when treating C-reactive protein as a continuous variable and controlling for baseline BP . CONCLUSION C-reactive protein levels are associated with future development of hypertension , which suggests that hypertension is in part an inflammatory disorder ", "CONTEXT Studies have demonstrated that statins administered to individuals with risk factors for coronary heart disease ( CHD ) reduce CHD events . However , many of these studies were too small to assess all-cause mortality or outcomes in important subgroups . OBJECTIVE To determine whether pravastatin compared with usual care reduces all-cause mortality in older , moderately hypercholesterolemic , hypertensive participants with at least 1 additional CHD risk factor . DESIGN AND SETTING Multicenter ( 513 primarily community-based North American clinical centers ) , r and omized , nonblinded trial conducted from 1994 through March 2002 in a subset of participants from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) . PARTICIPANTS Ambulatory persons ( n = 10 355 ) , aged 55 years or older , with low-density lipoprotein cholesterol ( LDL-C ) of 120 to 189 mg/dL ( 100 to 129 mg/dL if known CHD ) and triglycerides lower than 350 mg/dL , were r and omized to pravastatin ( n = 5170 ) or to usual care ( n = 5185 ) . Baseline mean total cholesterol was 224 mg/dL ; LDL-C , 146 mg/dL ; high-density lipoprotein cholesterol , 48 mg/dL ; and triglycerides , 152 mg/dL. Mean age was 66 years , 49 % were women , 38 % black and 23 % Hispanic , 14 % had a history of CHD , and 35 % had type 2 diabetes . INTERVENTION Pravastatin , 40 mg/d , vs usual care . MAIN OUTCOME MEASURES The primary outcome was all-cause mortality , with follow-up for up to 8 years . Secondary outcomes included nonfatal myocardial infa rct ion or fatal CHD ( CHD events ) combined , cause-specific mortality , and cancer . RESULTS Mean follow-up was 4.8 years . During the trial , 32 % of usual care participants with and 29 % without CHD started taking lipid-lowering drugs . At year 4 , total cholesterol levels were reduced by 17 % with pravastatin vs 8 % with usual care ; among the r and om sample who had LDL-C levels assessed , levels were reduced by 28 % with pravastatin vs 11 % with usual care . All-cause mortality was similar for the 2 groups ( relative risk [ RR ] , 0.99 ; 95 % confidence interval [ CI ] , 0.89 - 1.11 ; P = .88 ) , with 6-year mortality rates of 14.9 % for pravastatin vs 15.3 % with usual care . CHD event rates were not significantly different between the groups ( RR , 0.91 ; 95 % CI , 0.79 - 1.04 ; P = .16 ) , with 6-year CHD event rates of 9.3 % for pravastatin and 10.4 % for usual care . CONCLUSIONS Pravastatin did not reduce either all-cause mortality or CHD significantly when compared with usual care in older participants with well-controlled hypertension and moderately elevated LDL-C. The results may be due to the modest differential in total cholesterol ( 9.6 % ) and LDL-C ( 16.7 % ) between pravastatin and usual care compared with prior statin trials supporting cardiovascular disease prevention", "OBJECTIVE To investigate whether xuezhikang has additional beneficial effect on lipid peroxidation , myocardial fibrosis , inflammation and blood pressure control in hypertensive patients without sever hyperlipidemia treated with extended-released nifedipine . METHODS This is a r and omized , single-blind , placebo-controlled study , 100 patients with primary hypertension ( HT ) and normal or lightly elevated cholesterol level were r and omized to receive placebo ( n=49 ) or xuezhikang ( 1200 mg/d , n=51 ) for 24 weeks on top of extended-released nifedipine ( 20 mg , bid ) , 30 healthy volunteers served as controls . Plasma was obtained at baseline and 24 weeks after therapy . Lipids , C-reactive protein ( CRP ) , malondialdehyde ( MDA ) , superoxide dismutase photo-inhibition rate ( SOD-PR ) and type I collagen carboxypropeptide ( PIP ) were measured . RESULTS Normal blood pressure ( xuezhikang treated patients and in 40 out of 49 placebo treated patients ( P Plasma CRP , MDA , SOD-PR and PIP were significantly higher in HT patients than those in normal controls . Plasma CRP , MDA , PIP and SOD-PR were significantly decreased in xuezhikang group while remained unchanged in placebo group after 24 weeks treatment . CONCLUSION In patients with primary hypertension without severe hyperlipidemia treated with nifedipine , xuezhikang treatment exerts additional beneficial effects including better blood pressure control , endothelial function improvement , lipid oxidation loading attenuation and anti-inflammation", "Hypertension is the most common condition seen in primary care and leads to myocardial infa rct ion , stroke , renal failure , and death if not detected early and treated appropriately . Patients want to be assured that blood pressure ( BP ) treatment will reduce their disease burden , while clinicians want guidance on hypertension management using the best scientific evidence . This report takes a rigorous , evidence -based approach to recommend treatment thresholds , goals , and medications in the management of hypertension in adults . Evidence was drawn from r and omized controlled trials , which represent the gold st and ard for determining efficacy and effectiveness . Evidence quality and recommendations were grade d based on their effect on important outcomes . There is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg ; however , there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal , or in those younger than 30 years for a diastolic goal , so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion . The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease ( CKD ) as for the general hypertensive population younger than 60 years . There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor , angiotensin receptor blocker , calcium channel blocker , or thiazide-type diuretic in the nonblack hypertensive population , including those with diabetes . In the black hypertensive population , including those with diabetes , a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy . There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes . Although this guideline provides evidence -based recommendations for the management of high BP and should meet the clinical needs of most patients , these recommendations are not a substitute for clinical judgment , and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient", "C-reactive protein ( CRP ) , an acute phase reactant and marker of inflammation , has been shown to be associated with CRP genetic variants and incident hypertension , but it is unclear whether this link is causal . We therefore conducted a prospect i ve , nested case – control study to examine the relationship between single-nucleotide polymorphisms ( SNPs ) within the CRP gene , circulating CRP levels and the development of hypertension . Plasma CRP levels and the genotypes of eight SNPs were determined in 2000 unrelated Shanghai residents , including 908 hypertensive individuals and 1092 normotensive individuals . Among the 1092 normotensives , 968 subjects were followed up for 2 years , during which 71 developed hypertension . Plasma CRP levels were independently associated with the development of hypertension in the follow-up study ( odds ratio per quartile=1.64 ; 95 % confidence interval : 1.18–2.26 ; P elevated CRP levels , and the minor alleles of rs1205 , rs1800947 and rs2246469 ( all P decreased CRP levels . A haplotype-based analysis strengthened the results of single-locus analysis . However , none of the SNPs or haplotypes was significantly associated with blood pressure , incident hypertension or changes between baseline and follow-up blood pressure levels . Taken together , our findings demonstrated that plasma CRP levels were substantially associated with common genetic variants in the CRP gene and could predict the development of hypertension . However , the relationship between genotype and CRP levels was not associated with a change in hypertension risk" ]	41189ca8-06ff-11f0-808a-c43d1ab1c353
This study aims to evaluate the effectiveness of primary care interventions to improve the detection and treatment of osteoporosis . Eight electronic data bases and six gray literature sources were search ed . R and omized controlled trials , controlled clinical trials , quasi-r and omized trials , controlled before – after studies , and interrupted time series written in English or French from 1985 to 2009 were considered . Eligible studies had to include patients at risk ( women ≥ 65 years , men ≥ 70 years , and men/women ≥ 50 years with at least one major risk factor for osteoporosis ) or at high risk ( men/women using oral glucocorticoids or with previous fragility fractures ) for osteoporosis and fractures . Outcomes included bone mineral density ( BMD ) testing , osteoporosis treatment initiation , and fractures . Data were pooled using a r and om effects model when applicable . Thirteen studies were included . The majority were multifaceted and involved patient educational material , physician notification , and /or physician education . Absolute differences in the incidence of BMD testing ranged from 22 % to 51 % for high-risk patients only and from 4 % to 18 % for both at-risk and high-risk patients . Absolute differences in the incidence of osteoporosis treatment initiation ranged from 18 % to 29 % for high-risk patients only and from 2 % to 4 % for at-risk and high-risk patients . Pooling the results of six trials showed an increased incidence of osteoporosis treatment initiation ( risk difference ( RD ) = 20 % ; 95 % CI : 7–33 % ) and of BMD testing and /or osteoporosis treatment initiation ( RD = 40 % ; 95 % CI : 32–48 % ) for high-risk patients following intervention . Multifaceted interventions targeting high-risk patients and their primary care providers may improve the management of osteoporosis , but improvements are often clinical ly modest	[ "OBJECTIVE To assess the impact of risk management activities on patient risk of glucocorticoid-induced osteoporosis . METHODS Ninety-six adult patients taking chronic glucocorticoid therapy in 15 community pharmacies . Patients in the control group received usual and customary care . Patients in the treatment pharmacies received education and an educational pamphlet about the risks of glucocorticoid-induced osteoporosis . In addition , the treatment group pharmacists monitored the patients ' drug therapy , to identify and address drug-related problems . Data including the glucocorticoid taken by the patient , medications , and osteoporosis risk factors were collected at baseline and after 9 months of monitoring , via Web-based survey completed in the pharmacy . Using an intent to treat approach , the pre-post frequency changes were compared with contrasts for presence of bisphosphonate therapy , presence of estrogen therapy , presence of calcium supplement , discussion of glucocorticoid-induced osteoporosis risk , discussion of bone density test , presence of bone mineral density test , reported inactivity , and reported low calcium diet . RESULTS The contrast was significant in favor of the treatment pharmacies for the frequency of patients taking a calcium supplement ( Control [ -6.9 % ] vs. Treatment [ 17.1 % ] , P increasing calcium supplementation among patients at risk for glucocorticoid-induced osteoporosis . Pharmacists who educate at-risk patients can impact the self-care of these patients", "Background Despite recommendations , osteoporosis screening rates among women aged 65 years and older remain low . We present results from a clustered , r and omized trial evaluating patient mailed reminders , alone and in combination with physician prompts , to improve osteoporosis screening and treatment . Methods Primary care clinics ( n = 15 ) were r and omized to usual care , mailed reminders alone , or mailed reminders with physician prompts . Study patients were females aged 65–89 years ( N = 10,354 ) . Using automated clinical and pharmacy data , information was collected on bone mineral density testing , pharmacy dispensings , and other patient characteristics . Unadjusted/adjusted differences in testing and treatment were assessed using generalized estimating equation approaches . Results Osteoporosis screening rates were 10.8 % in usual care , 24.1 % in mailed reminder , and 28.9 % in mailed reminder with physician prompt . Results adjusted for differences at baseline indicated that mailed reminders significantly improved testing rates compared to usual care , and that the addition of prompts further improved testing . This effect increased with patient age . Treatment rates were 5.2 % in usual care , 8.4 % in mailed reminders , and 9.1 % in mailed reminders with prompt . No significant differences were found in treatment rates between those receiving mailed reminders alone or in combination with physician prompts . However , women receiving usual care were significantly less likely to be treated . Conclusions The use of mailed reminders , either alone or with physician prompts , can significantly improve osteoporosis screening and treatment rates among insured primary care patients ( Clinical Trials.gov number NCT00139425 )", "Background Despite accurate diagnostic tests and effective therapies , the management of osteoporosis has been observed to be suboptimal in many setting s. We tested the effectiveness of an intervention to improve care in patients at-risk of osteoporosis . Design R and omized controlled trial . Participants Primary care physicians and their patients at-risk of osteoporosis , including women 65 years and over , men and women 45 and over with a prior fracture , and men and women 45 and over who recently used ≥90 days of oral glucocorticoids . InterventionA multifaceted program of education and reminders delivered to primary care physicians as well as mailings and automated telephone calls to patients . Outcome : Either undergoing a bone mineral density ( BMD ) testing or filling a prescription for a bone-active medication during the 10 months of follow-up . Results After the intervention , 144 ( 14 % ) patients in the intervention group and 97 ( 10 % ) patients in the control group received either a BMD test or filled a prescription for an osteoporosis medication . This represents a 4 % absolute increase and a 45 % relative increase ( 95 % confidence interval 9–93 % , p = 0.01 ) in osteoporosis management between the intervention and control groups . No differences between groups were observed in the incidence of fracture . Conclusion An intervention targeting primary care physicians and their at-risk patients increased the frequency of BMD testing and /or filling prescriptions for osteoporosis medications . However , the absolute percentage of at-risk patients receiving osteoporosis management remained low", "UNLABELLED We conducted a r and omized controlled trial within the setting of a large drug benefit plan for Medicare beneficiaries . Primary care physicians and their patients were r and omized to usual care , patient intervention only , physician intervention only , or both interventions . There was no difference in the probability of the primary composite endpoint ( BMD test or osteoporosis medication ) or in either of its components comparing the combined intervention group with usual care ( risk ratio = 1.04 ; 95 % CI , 0.85 - 1.26 ) . INTRODUCTION Fractures from osteoporosis are associated with substantial morbidity , mortality , and cost . However , only a minority of at-risk older adults receives screening and /or treatment for this condition . We evaluated the effect of educational interventions for osteoporosis targeting at-risk patients , primary care physicians , or both . MATERIAL S AND METHODS We conducted a r and omized controlled trial within the setting of a large drug benefit plan for Medicare beneficiaries . Primary care physicians and their patients were r and omized to usual care , patient intervention only , physician intervention only , or both interventions . The at-risk patients were women > or=65 yr of age , men and women > or=65 yr of age with a prior fracture , and men and women > or=65 yr of age who used oral glucocorticoids . The primary outcome studied was a composite of either undergoing a BMD test or initiating a medication used for osteoporosis . The secondary outcome was a hip , humerus , spine , or wrist fracture . RESULTS We r and omized 828 primary care physicians and their 13,455 eligible at-risk patients into four study arms . Physician and patient characteristics were very similar across all four groups . Across all four groups , the rate of the composite outcome was 10.3 per 100 person-years and did not differ between the usual care and the combined intervention groups ( p = 0.5 ) . In adjusted Cox proportional hazards models , there was no difference in the probability of the primary composite endpoint comparing the combined intervention group with usual care ( risk ratio = 1.04 ; 95 % CI , 0.85 - 1.26 ) . There was also no difference in either of the components of the composite endpoint . The probability of fracture during follow-up was 4.2 per 100 person-years and did not differ by treatment assignment ( p = 0.9 ) . CONCLUSIONS In this trial , a relatively brief program of patient and /or physician education did not work to improve the management of osteoporosis . More intensive efforts should be considered for future quality improvement programs for osteoporosis", "We have assessed the acceptability of a method for screening for risk of future hip fracture in elderly women . After receipt of an initial response to a mailed risk-factor question naire sent out to 5,306 women , women were r and omly assigned to active or control groups . The active group was invited to participate in a screening visit that comprised a life-style question naire and a quantitative ultrasound heel scan . General practitioners ( GPs ) of women who were found to be in the lowest quartile of broadb and ultrasound attenuation and /or who had two or more risk factors for hip fracture were advised to prescribe a calcium and vitamin D supplement . A second mailed question naire was sent to both groups 1 to 3 years later . Compared with the control group , the active group had a 56 % lower risk of fracture ( odds ratio [ OR ] , 0.44 ; 95 % confidence interval [ CI ] , 0.24–0.81 adjusted age , weight , and treatment status ) . At follow-up , the proportion of fallers in the active group ( 25.3 % ) was lower than that in the control group ( 29.6 % ) ( P = 0.064 ) . The control group was found to have a higher rate of falls at follow-up than the active group ( 95 % CI , 0.02–0.22 ) ; no difference was found at baseline ( 95 % CI , −0.08 to + 0.14 ) . The screening method used was found to be acceptable to the majority of elderly women in this study . Screening the elderly in this way together with simple advice on treatment appears to reduce the age-associated increase in fall rates and the number of subsequent fractures . This form of screening may provide a cost-effective method to reduce falls and fractures in free-living elderly women . However , no such cost-effectiveness analysis has been performed to date", "Background Bisphosphonates can reduce fracture risk in patients with osteoporosis , but many at-risk patients do not start or adhere to these medications . The aims of this study are to : ( 1 ) preliminarily evaluate the effect of an individualized 10-year osteoporotic fracture risk calculator and decision aid ( OSTEOPOROSIS CHOICE ) for postmenopausal women at risk for osteoporotic fractures ; and ( 2 ) assess the feasibility and validity ( i.e. , absence of contamination ) of patient-level r and omization ( vs. cluster r and omization ) in pilot trials of decision aid efficacy . Methods / Design This is a protocol for a parallel , 2-arm , r and omized trial to compare an intervention group receiving OSTEOPOROSIS CHOICE to a control group receiving usual primary care . Postmenopausal women with bone mineral density T-scores of receiving bisphosphonate therapy , and receiving care at participating primary care practice s in and around Rochester , Minnesota , USA will be eligible to participate in the trial . We will measure the effect of OSTEOPOROSIS CHOICE on five outcomes : ( a ) patient knowledge regarding osteoporosis risk factors and treatment ; ( b ) quality of the decision-making process for both the patient and clinician ; ( c ) patient and clinician acceptability and satisfaction with the decision aid ; ( d ) rate of bisphosphonate use and adherence , and ( e ) trial processes ( e.g. , ability to recruit participants , collect patient outcomes ) . To capture these outcomes , we will use patient and clinician surveys following each visit and video recordings of the clinical encounters . These video recordings will also allow us to determine the extent to which clinicians previously exposed to the decision aid were able to recreate elements of the decision aid with control patients ( i.e. , contamination ) . Pharmacy prescription profiles and follow-up phone interviews will assess medication start and adherence at 6 months . Discussion This pilot trial will provide evidence of feasibility , validity of patient r and omization , and preliminary efficacy of a novel approach -- decision aids -- to improving medication adherence for postmenopausal women at risk of osteoporotic fractures . The results will inform the design of a larger trial that could provide more precise estimates of the efficacy of the decision aid . Trial registration Clinical Trials.gov Identifier :", "Background : Primary care physicians often fail to diagnose low bone density . This pilot study assessed 2 interventions for their effect on bone mineral density testing . Methods : Five practice s in the Iowa Research Network were r and omized : 2 to chart reminder alone ( CR ) , 2 to chart reminder plus mailed patient education ( CR+PtEd ) , and one to usual care . A total of 204 women aged 65 years or older were recruited from within these practice s. Bayesian hierarchical analyses were used instead of traditional statistical methods to take advantage of collateral data and to adjust for differences between clinics at baseline . Results : After the intervention , the rates of completed bone mineral density testing were 45.2 % in the CR+PtEd group , 31.4 % in the chart remainder only group , and 9.7 % in the usual care practice . Bayesian analysis adjusted for patient and clinic characteristics , which made use of collateral data , gave an odds ratio of 5.47 for the effect of CR+PtEd group . The Bayesian P was .029 and the one-sided 95 % credible interval for the odds ratio was greater than 1.2 . The effect of CR+PtEd was confirmed by sensitivity analyses . Traditional hierarchical analysis adjusted for practice characteristics could not be used to estimate statistical significance because there were not enough clinics to accommo date a model that included all the important covariables . Conclusions : Specific chart reminders to physicians combined with mailed patient education substantially increased the levels of bone density testing and could potentially be used to improve osteoporosis screening in primary care . Bayesian hierarchical analysis makes it possible to assess practice -level interventions when few practice s are r and omized", "Summary Osteoporosis is an increasing burden on individuals and health re sources . The Osteoporosis Prevention and Self-Management Course ( OPSMC ) was design ed to assist individuals to prevent and manage osteoporosis ; however , it had not been evaluated in an Australian setting . This r and omised controlled trial showed that the course increased osteoporosis knowledge . Introduction and hypothesisOsteoporosis is a major and growing public health concern . An OPSMC was design ed to provide individuals with information and skills to prevent or manage osteoporosis , but its effectiveness has not previously been evaluated . This study aim ed to determine whether OPSMC attendance improved osteoporosis knowledge , self-efficacy , self-management skills or behaviour . Material s and methods Using a wait list r and omised controlled trial design , 198 people ( 92 % female ) recruited from the community and aged over 40 ( mean age = 63 ) were r and omised into control ( n = 95 ) and intervention ( n = 103 ) groups . The OPSMC consists of four weekly sessions which run for 2 h and are led by two facilitators . The primary outcome were osteoporosis knowledge , health-directed behaviour , self-monitoring and insight and self-efficacy . Results The groups were comparable at baseline . At 6-week follow-up , the intervention group showed a significant increase in osteoporosis knowledge compared with the control group ; mean change 3.5 ( p health-directed behaviour , mean change 0.16 ( p < 0.05 ) , on a measure of 0–6 . Conclusion The results indicate that the OPSMC is an effective intervention for improving underst and ing of osteoporosis and some aspects of behaviour in the short term", "Background Osteoporosis-related fractures are a significant public health concern . Interventions that increase detection and treatment of osteoporosis , as well as prevention of fractures and falls , are substantially underutilized . This paper outlines the protocol for a pragmatic r and omised trial of a multifaceted community-based care program aim ed at optimizing the evidence -based management of falls and fractures in patients at risk . Design 6-month r and omised controlled study . Methods This population -based study was completed in the Algoma District of Ontario , Canada a geographically vast area with Sault Ste Marie ( population 78 000 ) as its main city . Eligible patients were allocated to an immediate intervention protocol ( IP ) group , or a delayed intervention protocol ( DP ) group . The DP group received usual care for 6 months and then was crossed over to receive the interventions . Components of the intervention were directed at the physicians and their patients and included patient-specific recommendations for osteoporosis therapy as outlined by the clinical practice guidelines developed by Osteoporosis Canada , and falls risk assessment and treatment . Two primary outcomes were measured including implementation of appropriate osteoporosis and falls risk management . Secondary outcomes included quality of life and the number of falls , fractures , and hospital admissions over a twelve-month period . The patient is the unit of allocation and analysis . Analyses will be performed on an intention to treat basis . Discussion This paper outlines the protocol for a pragmatic r and omised trial of a multi-faceted , community-based intervention to optimize the implementation of evidence based management for patients at risk for falls and osteoporosis . Trial Registration This trial has been registered with clinical trials.gov ( ID : NCT00465387", "Background and aims : Osteoporosis and fall fractures are increasing problems amongst the elderly . The aim of this study was to explore whether combined population -based and individual interventions directed at risk factors for osteoporosis and falls result in behavioral changes in an elderly population . Methods : A quasi-experimental design was used for the study . Persons aged ≥65 years were r and omly selected in the intervention and control community . An intervention program was managed from the primary health care center and delivered to the community . Health education was design ed to increase awareness of risk factors for the development of osteoporosis and falling . Question naires about lifestyle , health , previous fractures , safety behavior and physical activity level were distributed at baseline in 1989 and at the follow-ups in 1992 and 1994 in both communities . Results : There was a difference of 17.7 % between the dual intervention ( receiving both population -based and individual interventions ) and the control sample s regarding the self-reported use of shoe/cane spikes , and a difference of 20.5 % regarding the reported “ moderate level ” of physical activity in 1994 . There was an increase in the number of participants in the dual intervention sample who , at baseline , had not reported equipping their homes with non-slip mats and removing loose rugs but who did report these changes in 1994 . The increase in the reported use of shoe/cane spikes in the dual intervention sample was observed mainly for the period 1992–1994 . Conclusions : A public health intervention model , including both population -based and individual inter- ventions , can contribute to behavioral changes in the prevention of falls and changed physical activity patterns amongst elderly people", "Introduction Osteoporosis represents a growing public health concern ; however , current rates of management are sub-optimal . The aim of our study was to assess , in a r and omized controlled trial , the effect of a mailed educational intervention on older adults ’ knowledge , attitudes , and preventive behaviors regarding osteoporosis . The setting was a large publicly funded state pharmacy benefits program . The patients were 31,715 Medicare beneficiaries from Pennsylvania who participated in a drug benefits program for low-to-moderate income elderly people . Methods All women aged over 65 years , and all men and women with a history of fracture or long-term oral use of glucocorticoid , were included . Approximately half of the participants ( intervention group ) were r and omly selected to receive three mailings aim ed at improving knowledge of osteoporosis and enhancing preventive activities , such as using calcium and vitamin D , reducing fall risks in the home , obtaining a bone mineral density ( BMD ) test , and taking medications when necessary . The other participants did not receive the intervention mailings and served as controls . We surveyed a sample of intervention and control subjects to determine the effects of the intervention on knowledge , attitudes , self-efficacy ( confidence in one ’s ability to perform specific activities ) , and behavior regarding osteoporosis prevention and treatment . Six hundred r and omly selected participants in the intervention group and an equal number in the control group were invited to participate . Results Twenty-six had died and 636 of the remaining 1,185 ( 54 % ) completed the survey . Respondents and non-respondents did not differ significantly with respect to measured sociodemographic factors . All scales had good reliability ( all Cronbach ’s alphas > 0.65 ) . Knowledge of osteoporosis was generally very good and did not differ between intervention ( mean = 65 % correct responses ) and control subjects ( mean = 67 % correct ; P=0.4 ) . Perceived susceptibility to osteoporosis was relatively high and similar across groups ( P=0.4 ) . Self-efficacy for participating in osteoporosis prevention and treatment was very strong in both the intervention ( mean = 4.3 on a 0–5 scale ) and control ( mean = 4.2 , P=0.03 ) groups . On average , subjects in the intervention group reported participating in 3.5 of 6 preventive osteoporosis activities compared with 3.4 in the control group ( P=0.5 ) . Conclusions Compared with the controls , a mailed educational intervention for osteoporosis was not associated with better knowledge , higher perceived susceptibility , or performance of preventive measures among the at-risk older adults that we studied . The intervention group demonstrated a small increase in self-efficacy . More intensive patient interventions or intervention aim ed at other aspects of the care process may be required to bring about changes that lead to a reduction in fractures", "BACKGROUND In light of widespread undertreatment for glucocorticoid-induced osteoporosis ( GIOP ) , we design ed a group r and omized controlled trial to increase bone mineral density ( BMD ) testing and osteoporosis medication prescribing among patients receiving long-term glucocorticoid therapy . METHODS Using administrative data bases of a large US health plan , we identified physicians who prescribed long-term glucocorticoid therapy to at least 3 patients . One hundred fifty-three participating physicians were r and omized to receive a 3-module Web-based GIOP intervention or control course . Intervention modules focused on GIOP management and incorporated case-based continuing medical education and personalized audit and feedback of GIOP management compared with that of the top 10 % of study physicians . In the year following the intervention , we compared rates of BMD testing and osteoporosis medication prescribing between intervention and control physicians . RESULTS Following the intervention , intent-to-treat analyses showed that 78 intervention physicians ( 472 patients ) vs 75 control physicians ( 477 patients ) had similar rates of BMD testing ( 19 % vs 21 % , P = .48 ; rate difference , -2 % ; 95 % confidence interval [ CI ] , -8 % to 4 % ) and osteoporosis medication prescribing ( 32 % vs 29 % , P = .34 ; rate difference , 3 % ; 95 % CI , -3 % to 9 % ) . Among 45 physicians completing all modules ( 343 patients ) , intervention physicians had numerically but not significantly higher rates of BMD testing ( 26 % vs 16 % , P = .04 ; rate difference , 10 % ; 95 % CI , 1%-20 % ) and bisphosphonate prescribing ( 24 % vs 17 % , P = .09 ; rate difference , 7 % ; 95 % CI , -1 % to 16 % ) or met a combined end point of BMD testing or osteoporosis medication prescribing ( 54 % vs 44 % , P = .07 ; rate difference , 10 % ; 95 % CI , -1 % to 21 % ) compared with control physicians . CONCLUSIONS In the main analysis , a Web-based intervention incorporating performance audit and feedback and case-based continuing medical education had no significant effect on the quality of osteoporosis care . However , dose-response trends showed that physicians with greater exposure to the intervention had higher rates of GIOP management . New cost-effective modalities are needed to improve the quality of osteoporosis care", "Introduction Older patients with fragility fractures are not commonly tested or treated for osteoporosis . Compared to usual care , a previously reported intervention led to 30 % absolute increases in osteoporosis treatment within 6 months of wrist fracture . Our objective was to examine longer-term outcomes , reproducibility , and cost-effectiveness of this intervention . Methods We conducted an extended analysis of a non-r and omized controlled trial with blinded ascertainment of outcomes that compared a multifaceted intervention to usual care controls . Patients > 50 years with a wrist fracture treated in two Emergency Departments in the province of Alberta , Canada were included ; those already treated for osteoporosis were excluded . Overall , 102 patients participated in this study ( 55 intervention and 47 controls ; median age : 66 years ; 78 % were women ) . The interventions consisted of faxed physician reminders that contained osteoporosis treatment guidelines endorsed by opinion leaders and patient counseling . Controls received usual care ; at 6-months post-fracture , when the original trial was completed , all controls were crossed-over to intervention . The main outcomes were rates of osteoporosis testing and treatment within 6 months ( original study ) and 1 year ( delayed intervention ) of fracture , and 1-year persistence with treatments started . From the perspective of the healthcare payer , the cost-effectiveness ( using a Markov decision-analytic model ) of the intervention was compared with usual care over a lifetime horizon . Results Overall , 40 % of the intervention patients ( vs. 10 % of the controls ) started treatment within 6 months post-fracture , and 82 % ( 95%CI : 67–96 % ) had persisted with it at 1-year post-fracture . Delaying the intervention to controls for 6 months still led to equivalent rates of bone mineral density ( BMD ) testing ( 64 vs. 60 % in the original study ; p = 0.72 ) and osteoporosis treatment ( 43 vs. 40 % ; p = 0.77 ) as previously reported . Compared with usual care , the intervention strategy was dominant – per patient , it led to a $ 13 Canadian ( U.S. $ 9 ) cost savings and a gain of 0.012 quality -adjusted life years . Base-case results were most sensitive to assumptions about treatment cost ; for example , a 50 % increase in the price of osteoporosis medication led to an incremental cost-effectiveness ratio of $ 24,250 Canadian ( U.S. $ 17,218 ) per quality -adjusted life year gained . Conclusions A pragmatic intervention directed at patients and physicians led to substantial improvements in osteoporosis treatment , even when delivered 6-months post-fracture . From the healthcare payer ’s perspective , the intervention appears to have led to both cost-savings and gains in life expectancy", "OBJECTIVE To assess the effectiveness of a multifaceted intervention to improve the management of glucocorticoid-induced osteoporosis ( GIOP ) . METHODS Of 21 rheumatologists , 11 were r and omly assigned to a 3-part intervention consisting of a lecture and discussion regarding optimal management of GIOP , a confidential doctor-specific audit regarding management of GIOP , and a reminder mailing including concise pharmacologic recommendations . The remaining 10 rheumatologists received no special education . Patients with rheumatoid arthritis ( RA ) taking oral glucocorticoids seen in the 2 months after the intervention were followed for 6 months . Medical records were assessed to determine the proportion undergoing bone mineral density testing or receiving pharmacologic interventions for GIOP during the 6 months before and 6 months after the intervention . RESULTS There were 373 patients with RA taking oral glucocorticoids whose records were assessed . Patients in both arms of the trial were similar with respect to age , sex , menopausal status , glucocorticoid dosage and duration , duration of RA , disease-modifying antirheumatic drug use , and the proportion with comorbid conditions . At baseline , there was no significant difference between the patients with respect to osteoporosis medication use ( intervention 32 % versus control 34 % ) or bone densitometry use ( intervention 9 % versus control 5 % ) . After the intervention and a 6-month followup period , there were no differences in treatment ( intervention 33 % versus control 38 % ) or bone densitometry use ( intervention 8 % versus control 8 % ) . Adjusting for patient and physician characteristics did not significantly change these results . CONCLUSION A multifaceted intervention for GIOP , including doctor education , practice audit , and treatment suggestions , had no significant benefit on testing or treatment by rheumatologists over a 6-month followup period . Other intervention approaches need to be tested", "Although osteoporosis is common in older adults , it is often under-diagnosed and under-treated . We developed community-based patient- and physician-directed interventions for fracture prevention and compared them in a 2 x 2 factorial r and omized controlled trial . The study population included older adults who were enrolled in a state-run pharmacy benefits program ( The Pharmaceutical Assistance Contract for the Elderly in Pennsylvania ) for Medicare beneficiaries . We r and omly assigned 826 primary care physicians and their 31,715 patients to one of four trial arms -- no patient and no physician intervention , patient but no physician intervention , physician but no patient intervention , both patient and physician interventions . The patient intervention consisted of targeted communication about fall and fracture prevention and osteoporosis diagnosis and treatment . It was delivered through several mailings . The physician intervention entailed one-on-one academic detailing encounters covering the same topics . The composite primary endpoint consisted of use of osteoporosis medication or a bone mineral density test . Other endpoints included patient 's knowledge and attitudes towards fractures and osteoporosis , use of lower extremity strengthening to prevent falls , and the occurrence of fractures . All outcomes will be analyzed using r and om effects models accounting for clustering of subjects within physicians ' practice", "OBJECTIVES Osteoporosis treatment rates after a fracture are low . This study evaluated methods to increase guideline -recommended osteoporosis care postfracture . DESIGN Participants were r and omly assigned to usual care or one of two interventions . Analysis of primary outcomes used electronic data and linear regression . SETTING A Pacific Northwest nonprofit health maintenance organization . PARTICIPANTS Female patients aged 50 to 89 who suffered a fracture in 1999 and had not received bone mineral density ( BMD ) measurement or medication for osteoporosis ( n=311 ) and their primary care providers ( n=159 ) . INTERVENTION Patient-specific clinical guideline advice to the primary care provider delivered by electronic medical record ( EMR ) message or electronic reminder to the provider plus an educational letter mailed to the patient . MEASUREMENTS BMD measurement and osteoporosis medication . RESULTS At 6 months , provider reminder result ed in 51.5 % of patients receiving BMD measurement or osteoporosis medication , provider reminder plus patient education result ed in 43.1 % , and usual care result ed in 5.9 % ( P Patients aged 60 to 69 were 18 % ( 95 % confidence interval=3 - 34 ) more likely to receive BMD measurement or an osteoporosis medication than those aged 80 to 89 . CONCLUSION Patient-specific postfracture advice to the provider through an EMR message significantly increased BMD measurement and osteoporosis medication . As EMRs become more widespread , this intervention could improve osteoporosis management for many postfracture patients . Future research should identify barriers to and facilitators of care for older , high-risk patients", "OBJECTIVE To assess current osteoporosis treatment guidelines , studies of osteoporosis treatment , and interventions to improve osteoporosis treatment . METHODS We search ed the medical literature for articles published between January 1 , 1992 , and December 31 , 2003 , and assessed all relevant articles using a structured data abstract ion process . Because of substantial heterogeneity in study design , no attempt was made to summarize the data using meta-analytic techniques . RESULTS Seventy-six articles met criteria for inclusion . Eighteen practice guidelines were studied . Most guidelines were consistent in key treatment recommendations . Among 18 studies of treatment rates in patients who had fractures , the weighted average varied from 22 % for nonhormonal treatment to 19 % for calcium . We found slightly higher treatment rates for patients taking oral glucocorticoids or for those older than 65 years . There were no consistent correlates of which patients received treatment . Six studies that examined treatment frequencies after bone densitometry all found that patients with lower bone mineral density were more likely to receive treatment . Most of the 8 interventions design ed to improve osteoporosis treatment showed improvement in treatment rates ; however , only 3 were r and omized , and these showed the smallest effects . CONCLUSIONS Frequency of treatment of osteoporosis in at-risk population s is low . However , our assessment of the literature revealed no clear and consistent predictors of undertreatment . Few carefully controlled interventions have been reported", "Summary In a cluster r and omized trial , we evaluated the effect of a multifaceted intervention ( directed at both patient and primary care physician ) on the rates of testing and treatment of osteoporosis in postmenopausal women within six months of their wrist fracture . Compared to usual care , women in the intervention practice s were three times more likely to receive bone mineral density testing and prescribed osteoporosis treatments . Introduction Postmenopausal women with wrist fractures are at increased risk of future fragility fractures , yet they frequently do not receive evaluation and treatment for osteoporosis . We set out to evaluate a multifaceted intervention design ed to improve management of osteoporosis in older women with recent wrist fractures . Methods Cluster r and omized trial of 270 women cared for in 119 primary care practice s. We recruited postmenopausal women with an acute wrist fracture from the emergency departments of hospitals in southeastern Ontario , Canada . Family practice s were r and omly assigned to either the intervention or usual care . The intervention consisted of a mailed reminder with a summary of treatment guidelines and letter sent to the primary care physician , in addition to an educational package and letter to the women . The primary outcome was the proportion of women prescribed osteoporosis therapy within 6 months of their fracture . Results The mean age of women was 69(10.9 ) years . The intervention increased the proportion of women started on osteoporosis medications ( 28 % vs. 10 % ) of controls , adjusted OR 3.45 , 95 % CI , 1.58–7.56 , p = 0.002 ) and the proportion who had a bone mineral density ( BMD ) test ( 53.3 % vs. 26 % ) of controls , OR 3.38 , 95 % CI , 1.83–6.26 , p testing and treatment rates . Conclusion A multifaceted intervention significantly improved rates of osteoporosis treatment and BMD testing in postmenopausal women with wrist fractures", "OBJECTIVE We aim ed to determine whether a novel Patient Empowerment and Physician Alerting ( PEPA ) intervention would improve the proportion of seniors who were investigated and treated for osteoporosis after hip fracture . METHODS We undertook a 6-month r and omized controlled trial ( RCT ) in 48 women and men > /= 60 years old who had suffered a hip fracture and were admitted to a tertiary-care university hospital . The primary outcome measure was the proportion of participants offered one or more osteoporosis-specific ' best practice s ' measured using the Diagnosis and Management Question naire ( DMQ ) . Participant responses were vali date d in part by physician report . RESULTS In the PEPA intervention group , 19 ( 68 % ) were offered one or more components of best practice care compared with 7 ( 35 % ) in the ' usual care ' group ( p PEPA group , 15 ( 54 % ) ( p bisphosphonate therapy , 8 ( 29 % ) ( p bone mineral density scan , 11 ( 39 % ) were prescribed calcium and vitamin D ( p = .32 ) , and 9 ( 32 % ) ( p exercise . In the usual care group , 0 ( 0 % ) were prescribed bisphosphonate therapy , a bone mineral density assessment , or exercise and 6 ( 30 % ) were prescribed calcium and vitamin D. CONCLUSIONS This simple , inexpensive PEPA intervention result ed in far superior clinical management than did usual care in a population at high risk of future hip fracture", "OBJECTIVE To evaluate the effectiveness of a telephone-based \" virtual \" osteoporosis clinic in increasing the use of osteoporosis medication assessed at 1 year after receipt of a prescription . STUDY DESIGN R and omized controlled trial . METHODS Women 60 years and older with previously undiagnosed osteoporosis were r and omized to evaluation and treatment by a dedicated telephone-based osteoporosis clinic with monthly telephone follow-up until medication was successfully started ( intervention ) or to usual care provided by their primary care physician ( control ) . A successful outcome was defined as having filled a prescription for a 3-month supply of medication within 130 days , marking 1 year and 30 days since enrollment . RESULTS A total of 235 women underwent r and omization , and 211 received the allocation . Of 109 women in the telephone-based osteoporosis clinic group , 75 ( 68.8 % ) were using osteoporosis medication at 1 year compared with 46 of 102 women ( 45.1 % ) in the usual care group ( P knowledge about osteoporosis or attitude toward their osteoporosis care provider . The significant increase in osteoporosis medication use with the telephone intervention occurred at the same time that an independent health maintenance organization-wide program promoting osteoporosis treatment seemed to improve overall rates of use . CONCLUSIONS The use of osteoporosis medication among women with newly diagnosed osteoporosis may be significantly improved by a simple intervention based on monthly telephone follow-up . Overall use of osteoporosis medication in this trial may have been increased by a systemwide initiative to improve osteoporosis care conducted concurrently with the trial . ( Clinical Trials.gov Identifier : NCT00145067 . )", "Context Many patients who sustain fragility fractures do not receive subsequent testing and treatment for osteoporosis . Contribution This study shows that faxed reminders to physicians , treatment guidelines endorsed by opinion leaders , and patient education about osteoporosis can increase the testing and therapy for osteoporosis among patients who present to an emergency department with wrist fracture . Caution s This study did not r and omly assign persons to the intervention group and did not examine improvements in bone density or repeated fractures . The Editors Osteoporosis , a chronic and progressive condition that leads to decreased bone mass and skeletal fragility , may result in fractures , disability , pain , deformity , and even death ( 1 - 3 ) . The condition is common , affecting an estimated 1.4 million Canadians and 10 million Americans ( 1 , 2 ) . These figures represent 25 % of women and 12 % of men older than 50 years of age ( 1 , 2 ) . In the United States , the annual cost of treating osteoporosis and its sequelae has been estimated at $ 13.8 billion ( 2 ) , compared with $ 7.5 billion for congestive heart failure and $ 6.2 billion for asthma ( 3 ) . Without better preventive strategies , the rate of osteoporotic fractures is expected to double over the next 15 years ( 4 ) . Several experts ( 5 ) and guidelines ( 1 , 2 ) suggest a preventive strategy of identifying people with typical osteoporosis-related fractures ( for example , fractures of the hip , spine , or wrist [ often called fragility fractures ] ) and targeting them for treatment . They recommend this strategy because this population is at the greatest risk for subsequent fracture and may derive the greatest absolute benefit from treatment . Numerous safe and effective treatments can reduce the risk for recurrent fracture by 40 % to 60 % ( 1 - 3 , 6 ) . In addition , with the use of bisphosphonates and raloxifene , all subgroups of examined patients may obtain beneficial effects ( 3 , 7 - 9 ) within a year ( 7 , 8) . People 50 years of age and older with a fracture of the wrist may be particularly well suited to a strategy of case finding and secondary prevention . Fractures of the wrist are the most common symptomatic fracture related to osteoporosis ( 3 ) , and 70 % to 80 % of persons with wrist fractures have low bone mass ( 10 , 11 ) . Observational studies suggest that a wrist fracture is a sentinel event in the natural history of osteoporosis because this type of fracture forecasts an increased risk for fractures of the hip and spine over the next 10 to 20 years ( 12 - 14 ) . Best practice ( clinical practice consistent with current evidence and expert consensus ) would be to identify people 50 years of age or older with a fragility fracture of the wrist , to measure their bone mineral density , and to treat those with low bone mass or osteoporosis ( 1 , 2 , 5 ) . However , the gap between best practice and everyday clinical practice is wide . Over the past 5 to 10 years , studies from the United States ( 3 , 15 , 16 ) , Canada ( 17 , 18 ) , and elsewhere ( 5 , 19 ) report that rates of testing for and treating osteoporosis a year or longer after a fracture of the wrist are less than 10 % to 20 % . This is an important failure in the process of knowledge translation and indicates that benefits within our reach are not being achieved . We design ed a pragmatic , multifaceted osteoporosis intervention strategy directed at people 50 years of age or older with a fracture of the wrist and at their primary care physicians . The intervention consisted of physician reminders , treatment guidelines endorsed by local opinion leaders , and patient education . Our primary objective was to examine whether this intervention improved the diagnosis and treatment of osteoporosis in this high-risk population . Secondary objectives included examining the effect of this intervention on patients ' knowledge , satisfaction , and quality of life . Methods Setting and Participants Capital Health ( Edmonton , Alberta ) is one of the largest integrated health service delivery organizations in Canada ( 20 ) . It provides comprehensive health services for about 1 million people and has an annual budget of almost $ 2 billion ( Canadian ) ( 20 ) . Primary care is delivered by approximately 900 fee-for-service physicians . We enrolled participants from the 2 largest emergency departments in the region : the University of Alberta Hospital ( a university-based teaching hospital ) and the Royal Alex and ra Hospital ( a university-affiliated community teaching hospital ) . These emergency departments provide most of the fracture care and emergency orthopedic services to the region . Consecutive patients presenting to the emergency department with a wrist fracture were potentially eligible . Inclusion criteria were as follows : age 50 years or older ; any simple , closed fracture of the distal forearm ; and discharge home . We excluded patients who were already taking prescription treatments for osteoporosis . Because we did not ask patients whether they had a diagnosis of osteoporosis until study closeout , a patient with a history of osteoporosis who was not being treated with prescription medication was potentially eligible for inclusion . We also excluded patients who were unable to provide consent , were unwilling to participate , were admitted to the hospital , resided in a long-term care facility , resided outside the Capital Health region , or could not read and converse in English . Study Design and Patient Enrollment We conducted a prospect i ve controlled trial with blinded ascertainment of outcomes . To allocate patients to the intervention or usual care control groups , we adapted and modified an onoff 1-site study design for 2 sites ( 21 ) . For 1 month at a time , in sequential order , the intervention was on at 1 emergency department while it was off at the other . At the end of each month , research nurses alternated intervention status from on to off or vice versa . Patients with wrist fractures were treated , as appropriate , by emergency department physicians and then approached by research nurses or orthopedic technicians for enrollment in the study before discharge home . We obtained informed consent from each patient , and all data were maintained outside the emergency departments in a central ized secure file system . The University of Alberta Health Research Ethics Board approved the study . Intervention We design ed an intervention to overcome the many barriers that exist for primary care physicians who are trying to adopt evidence -based treatments for their patients with osteoporosis . Each of the 3 components of the intervention had published evidence of effectiveness ( 22 - 24 ) . Physician Reminders A reminder was generated for each patient and faxed to the primary care physician of record . The reminder notified physicians that their patient had recently been seen and treated in the emergency department for a wrist fracture and reminded them that their patient was now considered to be at increased risk for osteoporosis . Generating and sending the personalized and patient-specific reminder took about 6 minutes for each patient . Treatment Guidelines Generated and Endorsed by Opinion Leaders As part of the reminder , we provided brief evidence -based treatment recommendations . These guidelines were design ed to fit on the same page and emphasized 3 points : 1 ) The patient is at very high risk for osteoporosis and needs a bone mineral density measurement if one has not been performed in the past year ; 2 ) without treatment , the patient may be at increased risk for another fracture within the year ; and 3 ) bisphosphonate treatment will reduce the patient 's risk for fracture by about 50 % . Bisphosphonate alternatives ( for example , calcitonin , raloxifene , and hormone therapy ) were mentioned as second-line approved treatments because , at the time of study design , only the bisphosphonates had been demonstrated to prevent both vertebral and nonvertebral fractures . Using previously vali date d methods ( 25 , 26 ) , we recruited 5 osteoporosis opinion leaders who had been nominated by local primary care providers . The opinion leaders helped develop and then endorsed the guidelines by attaching their names and signatures . Patient Education We provided patients in the intervention group with a tailored , single-page summary of osteoporosis information that mirrored the physician material s described in the preceding paragraph . We reinforced these written material s with a brief telephone counseling session that took place within 1 week of the fracture . This counseling ( approximately 4 minutes per session ) reiterated the content of the written material s and encouraged patients to seek further information and counseling from their primary care physician . We did not provide intervention patients with any written material s or counseling regarding fall prevention or home safety . Control Patients ( Usual Care ) On the basis of surveys and in-depth interviews with emergency department physicians in Canada and the United States , the current st and ard of care for patients treated for a wrist fracture usually consists of 1 ) notification to the primary care physician of record that the patient was seen and treated and 2 ) information on follow-up plans . We ensured that such notifications occurred for all control patients . In addition , we enhanced usual care by ensuring that control patients received educational material s and telephone counseling regarding fall prevention and home safety . During the call , patients were encouraged to visit their primary care physician for more detailed advice and a medication review . They did not receive any counseling or educational material s about osteoporosis . Thus , control patients received the same amount of attention and care as the intervention patients . After the main study was completed , all control patients were crossed over to the osteoporosis intervention , and all intervention patients were provided with counseling regarding fall prevention and home safety . Outcomes and Measurements The primary study outcome was", "Summary This study evaluated the effect of a multifaceted intervention ( screening and patient education ) by community pharmacists on testing or treatment of osteoporosis . One hundred and twenty-nine patients r and omized to receive the intervention were compared to 133 patients who did not receive the intervention . Twice as many patients who got the intervention received further testing or treatment for osteoporosis . Introduction The objective of this study was to determine the effect of a community pharmacist screening program on testing and treatment of osteoporosis . Methods In this r and omized , controlled trial , 262 patients meeting bone mineral density ( BMD ) testing guidelines [ men or women aged ≥ 65 years or 50–64 years with one major risk factor including previous fracture , family history of osteoporosis , glucocorticoids for > 3 months , or early menopause ] were allocated to intervention ( 129 ) or control ( 133 ) . Intervention consisted of printed material s , education , and quantitative ultrasound . Primary outcome was a composite endpoint of BMD or prescription for osteoporosis medication within 4 months . Results Primary endpoint of BMD or osteoporosis treatment was achieved by 28 intervention patients ( 22 % ) compared with 14 controls ( 11 % ) ( RR 2.1 , 95 % CI 1.1–3.7 ) . This was driven by BMD testing ( 28 ( 22 % ) vs. 13 ( 10 % ) for controls , p = 0.011 ) . Calcium intake increased more among intervention patients than controls ( 30 % vs. 19 % , RR 1.6 , 95 % CI 1.0–2.5 ) . There was no effect on knowledge or quality of life . Conclusion A pharmacist screening program doubled the number of patients tested for osteoporosis . Nevertheless , many patients eligible for BMD did not receive appropriate care suggesting more intensive interventions are needed", "Background : Older patients who experience a fragility fracture are at high risk of future fractures but are rarely tested or treated for osteoporosis . We developed a multifaceted intervention directed at older patients with wrist fractures ( in the form of telephone-based education ) and their physicians ( in the form of guidelines endorsed by opinion leaders , supported by reminders ) to improve the quality of osteoporosis care . Methods : In a r and omized controlled trial with blinded ascertainment of outcomes , we compared our intervention with usual care ( provision of printed educational material s to patients ) . Eligible patients were those older than 50 years of age who had experienced a wrist fracture and were seen in emergency departments and fracture clinics ; we excluded those who were already being treated for osteoporosis . The primary outcome was bisphosphonate treatment within 6 months after the fracture . Secondary outcomes included bone mineral density testing , “ appropriate care ” ( consisting of bone mineral density testing with treatment if bone mass was low ) and quality of life . Results : We screened 795 patients for eligibility and r and omly assigned 272 to the intervention ( 137 patients ) or control ( 135 patients ) group . The median age was 60 years ; 210 ( 77 % ) of the subjects were women , and 130 ( 48 % ) reported a previous fracture as an adult . Six months after the fracture , 30 ( 22 % ) of the intervention patients , as compared with 10 ( 7 % ) of the control patients , were receiving bisphosphonate therapy for osteoporosis ( adjusted relative risk [ RR ] 2.6 , 95 % confidence interval [ CI ] 1.3–5.1 , p = 0.008 ) . Intervention patients were more likely than control patients to undergo bone mineral density testing ( 71/137 [ 52 % ] v. 24/135 [ 18 % ] ; adjusted RR 2.8 , 95 % CI 1.9–4.2 , p receive appropriate care ( 52/137 [ 38 % ] v. 15/135 [ 11 % ] ; adjusted RR 3.1 , 95 % CI 1.8–5.3 , p died , and 4 others experienced recurrent fracture . Interpretation : A multifaceted intervention directed at high-risk patients and their physicians substantially increased rates of testing and treatment for osteoporosis . Nevertheless , more than half of the patients in the intervention group were not receiving appropriate care 6 months after their fracture , which suggests that additional strategies should be explored . ( Clinical Trials.gov trial register no. NCT00152321 .", "BACKGROUND Patients who survive hip fracture are at high risk of recurrent fractures , but rates of osteoporosis treatment 1 year after sustaining a fracture are less than 10 % to 20 % . We have developed an osteoporosis case manager intervention . The case manager educated patients , arranged bone mineral density tests , provided prescriptions , and communicated with primary care physicians . The intervention was compared with usual care in a r and omized controlled trial . METHODS We recruited from all hospitals that participate in the Capital Health system ( Alberta , Canada ) , including patients 50 years or older who had sustained a hip fracture and excluding those who were receiving osteoporosis treatment or who lived in a long-term care facility . Primary outcome was bisphosphonate therapy 6 months after fracture ; secondary outcomes included bone mineral density testing , appropriate care ( bone mineral density testing and treatment if bone mass was low ) , and intervention costs . RESULTS We screened 2219 patients and allocated 220 , as follows : 110 to the intervention group and 110 to the control group . Median age was 74 years , 60 % were women , and 37 % reported having had previous fractures . Six months after hip fracture , 56 patients in the intervention group ( 51 % ) were receiving bisphosphonate therapy compared with 24 patients in the control group ( 22 % ) ( adjusted odds ratio , 4.7 ; 95 % confidence interval , 2.4 - 8.9 ; P Bone mineral density tests were performed in 88 patients in the intervention group ( 80 % ) vs 32 patients in the control group ( 29 % ) ( P bone mineral density testing , 25 ( 21 % ) had normal bone mass . Patients in the intervention group were more likely to receive appropriate care than were patients in the control group ( 67 % vs 26 % ; P intervention cost was $ 50.00 per patient . CONCLUSION For a modest cost , a case manager was able to substantially increase rates of osteoporosis treatment in a vulnerable elderly population at high risk of future fractures", "Recognizing Osteoporosis and its Consequences in Quebec ( ROCQ ) is an ongoing patient health-management programme aim ed at evaluating the diagnostic and treatment care gaps for osteoporosis following a fragility fracture , and subsequently initiating and measuring interventions to decrease these gaps in women 50 years of age and over . Hospitals servicing approximately half of the population of the Province of Quebec ( Canada ) are participating in the ROCQ programme . Women with fragility and traumatic fractures are approached during their visit to a cast or outpatient clinic and are subsequently contacted by telephone 0 to 16 weeks after their fracture ( phase 1 ) . During the first phone contact , they are invited to answer a question naire aim ed at identifying the specific circumstances of their fracture and asked to participate in an observational study that could last up to 18 months . Based on this initial question naire , patients are classified as having either experienced a fragility or traumatic fracture . During the first phone contact , there is no reference about the possible association between the fracture and osteoporosis and no investigation or intervention is proposed . Six to eight months after the fracture event ( phase 2 ) , women are again contacted by phone to complete a question naire that evaluates the diagnostic and treatment rates for osteoporosis . At this phase of the programme , women with fragility fractures are r and omized to one of the three following intervention groups : 1 ) Educational Video Group , 2 ) Documentation Group and 3 ) Control Group . Participants are contacted 12 to 14 months after the intervention ( phase 3 ) to evaluate the efficacy of the interventions on the diagnosis and treatment rates of osteoporosis . All participants with fragility or traumatic fractures who consent will be followed for 20 years using data from the Québec Ministry of Health data base to measure the association between the index fracture and future fracture risk", "This article reports a controlled trial to investigate the effectiveness of patient education and a physician alerting system in altering secondary osteoporosis prevention after a low-trauma ( fragility ) wrist fracture and to record the current rate of osteoporosis investigation following such fractures . Fifty-one women and men aged 50 years or older with a low-trauma wrist fracture were identified ( 41 women and 10 men ; mean age [ 95 % CI ] , 71.51 [ 67.31 - 74.81 ] ) . The intervention group received a four-part intervention aim ed at both the patient and the family physician in addition to the usual care for the fracture . The control group only received usual care for the fracture . Data were collected for both groups at six weeks and six months . Results indicate that 92 % of the intervention subjects were investigated for osteoporosis , compared with the usual-care group , in which only 23 % were investigated . Early osteoporosis intervention has the potential to limit disease impact , and h and therapists can play a key role in early identification of osteoporosis", "* The up date s are underlined for quick reference . INTRODUCTION A critical need exists for efficient , measurable systems of disease management that reconcile conflicts between socioeconomic responsibility and patient welfare . Clinical guidelines have become an important component of these systems because they address elements of care that are effective and that reduce the variability in our approach to patient management . The American Association of Clinical Endo-crinologists ( AACE ) 2001 Medical Guidelines for Clinical Practice for the Prevention and Management of Postmenopausal Osteoporosis address the prevention , diagnosis , and management of postmenopausal osteoporo-sis , a disorder that is recognized as a major public health problem because of its physical and socioeconomic consequences . They are intended to simplify medical decision making and to help physicians and their patients make good decisions about skeletal health and postmenopausal osteoporosis . The specific goals of these guidelines are to reduce the incidence of fractures related to osteoporosis and to achieve the highest quality of life for individual patients by using the most effective and efficient methods of diagnosis and management . In the preparation of this 2001 edition , reports in the peer- review ed literature dealing with prevention , diagnosis , and treatment of postmenopausal osteoporosis , which were published and indexed between 1996 ( the publication date of the previous edition of these guidelines ) and January 2001 , were identified by computer search , review ed , and grade d for clinical relevance and scientific merit . Although cost-effectiveness was carefully considered , variabilities in actual costs could not be accurately determined . Therefore , cost-effectiveness modeling was not undertaken . Whenever possible , recommendations were based on r and omized , prospect i ve , double-blind studies of well-defined patient population s. Studies that used the most relevant clinical endpoint , fracturing , were considered \" level 1 \" evidence . When level 1 evidence was not available , recommendations were based on cross-sectional studies , investigations that tested smaller or nonr and omized patient population s , or studies that tested secondary or surrogate clinical endpoints for fracture , such as bone mineral density ( BMD ) or bone turnover markers , in treated population s ( level 2 evidence ) . When stronger evidence was not available , review s , editorials , and expert opinions were used ( level 3 evidence ) . We recognize that the process of developing clinical guidelines necessarily results in a narrowing and codifica-tion of clinical choices , which can be inappropriate in some clinical situations . Because the application of objective information to the specific needs of patients is the ultimate responsibility of the practicing physician , clinical practice guidelines are not intended to be rigid or restrictive , nor", "OBJECTIVE We previously demonstrated that a case manager intervention improved osteoporosis ( OP ) treatment within 6 months of hip fracture compared with usual care . The second phase of the r and omized trial compared a less intensive intervention , facilitated bone mineral density ( BMD ) testing , with usual care and the case manager intervention . METHODS We initially r and omized 220 hip fracture patients to either an OP case manager intervention or usual care . After completing the original trial at 6 months postfracture , usual care patients were reallocated to facilitated BMD testing ; BMD tests were arranged and results sent to primary care physicians . Main outcomes ( bisphosphonate treatment , BMD tests , receipt of appropriate care ) were reascertained 1 year following hip fracture and compared with outcomes achieved by the OP case manager intervention and usual care . RESULTS Compared with usual care , facilitated BMD testing increased testing from 29 % to 68 % ( P bisphosphonate use from 22 % to 38 % ( P of appropriate care from 26 % to 45 % ( P OP case manager intervention led to significantly higher bisphosphonate use ( 54 % versus 38 % ; P = 0.03 ) , receipt of appropriate care ( 71 % versus 45 % ; P BMD testing ( 80 % versus 68 % ; P = 0.06 ) than usual care followed by facilitated BMD testing . CONCLUSION Compared with usual care , 2 different inexpensive interventions result ed in significant increases in appropriate management of OP after hip fracture . The magnitude of improvements achieved was directly related to the intensity of the interventions" ]	41189ce4-06ff-11f0-808a-c43d1ab1c353
AIM This paper is a report of a review conducted to provide an overview of the evidence in the literature on task-oriented training of stroke survivors and its relevance in daily nursing practice . BACKGROUND Stroke is the second leading cause of death and one of the leading causes of adult disability in the Western world . The use of neurodevelopmental treatment in the daily nursing care of stroke survivors does not improve clinical outcomes . Nurses are therefore exploring other forms of rehabilitation intervention , including task-oriented rehabilitation . Despite the growing number of studies showing evidence on task-oriented interventions , recommendations for daily nursing practice are lacking . DATA SOURCES A range of data bases was search ed to identify papers addressing task-oriented training in stroke rehabilitation , including Medline , CINAHL , Embase and the Cochrane Library of systematic review s. Papers published in English between January 1996 and September 2007 were included . There were 42 papers in the final data set , including nine systematic review s. REVIEW METHODS The selected r and omized controlled trials and systematic review s were assessed for quality . Important characteristics and outcomes were extracted and summarized . RESULTS Studies of task-related training showed benefits for functional outcome compared with traditional therapies . Active use of task-oriented training with stroke survivors will lead to improvements in functional outcomes and overall health-related quality of life . CONCLUSION Generally , task-oriented rehabilitation proved to be more effective . Many interventions are feasible for nurses and can be performed in a ward or at home . Nurses can and should play an important role in creating opportunities to practise meaningful functional tasks outside of regular therapy sessions	[ "CONTEXT Single-site studies suggest that a 2-week program of constraint-induced movement therapy ( CIMT ) for patients more than 1 year after stroke who maintain some h and and wrist movement can improve upper extremity function that persists for at least 1 year . OBJECTIVE To compare the effects of a 2-week multisite program of CIMT vs usual and customary care on improvement in upper extremity function among patients who had a first stroke within the previous 3 to 9 months . DESIGN AND SETTING The Extremity Constraint Induced Therapy Evaluation ( EXCITE ) trial , a prospect i ve , single-blind , r and omized , multisite clinical trial conducted at 7 US academic institutions between January 2001 and January 2003 . PARTICIPANTS Two hundred twenty-two individuals with predominantly ischemic stroke . INTERVENTIONS Participants were assigned to receive either CIMT ( n = 106 ; wearing a restraining mitt on the less-affected h and while engaging in repetitive task practice and behavioral shaping with the hemiplegic h and ) or usual and customary care ( n = 116 ; ranging from no treatment after concluding formal rehabilitation to pharmacologic or physiotherapeutic interventions ) ; patients were stratified by sex , prestroke dominant side , side of stroke , and level of paretic arm function . MAIN OUTCOME MEASURES The Wolf Motor Function Test ( WMFT ) , a measure of laboratory time and strength-based ability and quality of movement ( functional ability ) , and the Motor Activity Log ( MAL ) , a measure of how well and how often 30 common daily activities are performed . RESULTS From baseline to 12 months , the CIMT group showed greater improvements than the control group in both the WMFT Performance Time ( decrease in mean time from 19.3 seconds to 9.3 seconds [ 52 % reduction ] vs from 24.0 seconds to 17.7 seconds [ 26 % reduction ] ; between-group difference , 34 % [ 95 % confidence interval { CI } , 12%-51 % ] ; P MAL Amount of Use ( on a 0 - 5 scale , increase from 1.21 to 2.13 vs from 1.15 to 1.65 ; between-group difference , 0.43 [ 95 % CI , 0.05 - 0.80 ] ; P MAL Quality of Movement ( on a 0 - 5 scale , increase from 1.26 to 2.23 vs 1.18 to 1.66 ; between-group difference , 0.48 [ 95 % CI , 0.13 - 0.84 ] ; P self-perceived h and function difficulty ( Stroke Impact Scale h and domain ) vs a decrease of 10.1 for the control group ( between-group difference , 9.42 [ 95 % CI , 0.27 - 18.57 ] ; P=.05 ) . CONCLUSION Among patients who had a stroke within the previous 3 to 9 months , CIMT produced statistically significant and clinical ly relevant improvements in arm motor function that persisted for at least 1 year . Trial Registration clinical trials.gov Identifier : NCT00057018", "CONTEXT Reorganization in central motor networks occurs during early recovery from hemiparetic stroke . In chronic stroke survivors , specific rehabilitation therapy can improve upper extremity function . OBJECTIVE To test the hypothesis that in patients who have chronic motor impairment following stroke , specific rehabilitation therapy that improves arm function is associated with reorganization of cortical networks . DESIGN , SETTING , AND PATIENTS A r and omized controlled clinical trial conducted in a US ambulatory rehabilitation program with 21 patients ( median [ IQR ] , 50.3 [ 34.8 - 77.3 ] months after unilateral stroke ) . Data were collected between 2001 and 2004 . INTERVENTIONS Patients were r and omly assigned to bilateral arm training with rhythmic auditory cueing ( BATRAC ) ( n = 9 ) or st and ardized dose-matched therapeutic exercises ( DMTE ) ( n = 12 ) . Both were conducted for 1 hour , 3 times a week , for 6 weeks . MAIN OUTCOME MEASURES Within 2 weeks before and after the intervention , brain activation during elbow movement assessed by functional magnetic resonance imaging ( fMRI ) and functional outcome assessed using arm function scores . RESULTS Patients in the BATRAC group but not in the DMTE group increased hemispheric activation during paretic arm movement ( P = .03 ) . Changes in activation were observed in the contralesional cerebrum and ipsilesional cerebellum ( P = .009 ) . BATRAC was associated with significant increases in activation in pre central ( P fMRI changes . Considering all patients , there were no differences in functional outcome between groups . When only BATRAC patients with fMRI response were included ( n = 6 ) , BATRAC improved arm function more than DMTE did ( P = .02 ) . CONCLUSIONS These preliminary findings suggest that BATRAC induces reorganization in contralesional motor networks and provide biological plausibility for repetitive bilateral training as a potential therapy for upper extremity rehabilitation in hemiparetic stroke", "The purpose of this study was to compare the effects of a task-oriented exercise program with and without altered sensory input on postural stability in subjects with stroke . Sixteen hemiparetic subjects , at least 6 months post-stroke , were r and omly assigned to the experimental or control group , and participated in an 8-week task-oriented exercise program focusing on balance and mobility exercises . Exercises were performed under normal conditions by the control group , and under conditions of vision and surface manipulation by the experimental group . Pre- and post-test assessment s involved the measurement of the center of pressure ( COP ) displacement during double-legged stance and sit-to-st and under four sensory conditions : ( 1 ) eyes open , normal surface ; ( 2 ) eyes open , soft surface ; ( 3 ) eyes closed , normal surface ; and ( 4 ) eyes closed , soft surface , as well as the 10-m walking test . Results showed significant improvements ( P COP displacement under sensory conditions ( 1 ) and ( 2 ) for the experimental group only , and limited changes for the sit-to-st and in both groups after training . Significant improvements ( P task-oriented exercise program , assisted by sensory manipulation , is more effective at improving the st and ing balance of stroke subjects than a conventional task-oriented program . Die vorliegende Studie vergleicht die Wirkung eines anforderungsspezifischen Übungsprogramms mit und ohne Sinnesreizänderung auf die posturale Stabilität von Schlaganfallpatienten . Insgesamt 16 Hemiparetiker wurden mindestens sechs Monate nach dem Schlaganfall r and omisiert der Versuchs- oder der Kontrollgruppe zugeordnet , innerhalb derer sie acht Wochen an einem anforderungsspezifischen Programm mit speziellen Gleichgewichts- und Mobilitätsübungen teilnahmen . Die Kontrollgruppe führte die Übungen unter normalen Bedingungen durch , die Versuchsgruppe dagegen unter Manipulation der Aspekte Sicht und Gehflächen . Bei den Bewertungen vor und nach dem Test wurde die Verlagerung des Druckmittelpunkts ( COP ) während der zweibeinigen Haltung und der Aufstehübung anh and von vier Sinneszuständen gemessen : ( 1 ) offene Augen , normale Fläche , ( 2 ) offene Augen , weiche Fläche , ( 3 ) geschlossene Augen , normale Fläche und ( 4 ) geschlossene Augen , weiche Fläche sowie anh and des 10 m Gehtests . Die Ergebnisse wiesen nur bei der Versuchsgruppe bei der COP-Verlagerung unter den Sinneszuständen ( 1 ) und ( 2 ) beachtliche Verbesserungen ( P Verbesserungen ( P anforderungsspezifisches Übungsprogramm mit begleitender Sinnesmanipulation das Gleichgewicht von Schlaganfallpatienten bei aufrechter Körperhaltung effektiver verbessert als ein herkömmliches anforderungsspezifisches Programm . El propósito de este estudio fue comparar los efectos de un programa de ejercicios dirigidos , con estimulación sensorial alterada o sin ella , sobre la estabilidad postural de sujetos con accidente vascular cerebral . Dieciséis sujetos hemiparéticos que habían sufrido un accidente vascular cerebral hacía al menos 6 meses , fueron distribuidos al azar en dos grupos : uno experimental y uno control . Los mismos participaron durante 8 semanas en un programa de ejercicios dirigidos , el cual se centraba en ejercicios de balance y de movilidad . El grupo control realizó los ejercicios en condiciones normales , mientras que el grupo experimental los realizó en condiciones en que la visión y las superficies fueron alteradas . En las evaluaciones realizadas antes y después de los ejercicios se midió la desviación del centro de presión ( CP ) durante la postura de pie utiliz and o ambas piernas , así como en la postura sentada , listo para ponerse de pie , bajo cuatro condiciones sensoriales deferentes : 1 ) ojos abiertos , superficie normal ; 2 ) ojos abiertos , superficie bl and a ; 3 ) ojos cerrados , superficie normal ; y 4 ) ojos cerrados , superficie bl and a. Se realizó además la prueba de la marcha de los 10 m. Los result ados mostraron mejoras significativas ( P ejercicios dirigidos , en los que se utilicen manipulaciones sensoriales , es más efectivo que un programa convencional de ejercicios dirigidos para mejorar el balance durante la postura de pie en sujetos con accidente vascular cerebral . Le but de cette étude était de comparer les effets d'un programme d'exercices fonctionnels assistés ou non de stimulations sensorielles sur la stabilité posturale de sujets atteints d'un accident vasculaire cérébral ( AVC ) . Seize sujets hémiparétiques atteints d'un AVC depuis au moins 6 mois et répartis de façon aléatoire au sein du groupe expérimental et du groupe témoin ont participé à un programme d'exercices fonctionnels de huit semaines portant sur des exercices d'équilibre et de mobilité . Les exercices étaient exécutés en situation normale par le groupe témoin et en situation de manipulation de la vision et de la surface de support par le groupe expérimental . Les évaluations pré et post exercices ont été effectuées à l'aide de la mesure du déplacement du centre de pression ( CP ) lors du maintien de la position debout en appui bipodal et du transfert assis-debout selon les quatre conditions sensorielles suivantes : yeux ouverts , surface normale ( 1 ) ; yeux ouverts , surface moelleuse ( 2 ) ; yeux fermés , surface normale ( 3 ) ; yeux fermés , surface moelleuse ( 4 ) . Le test de marche de 10 mètres a aussi été inclus dans l'évaluation . Les résultats ont démontré une amélioration significative ( P du CP dans les conditions 1 et 2 pour le groupe expérimental seulement ainsi que des changements limités pour le transfert assis-debout chez les deux groupes de sujets à la suite de l'entraînement . Une amélioration significative ( P programme d'exercices fonctionnels assistés de stimulations sensorielles est plus efficace pour l'amélioration du maintien de l'équilibre en position debout chez les sujets atteints d'un AVC qu'un programme d'exercices fonctionnels conventionnnel ", "OBJECTIVE To examine rehabilitation interventions and result ing physical activity patterns of patients managed in acute stroke units to help inform development of a r and omized controlled trial of very early rehabilitation . DESIGN An open observational study of patient activity and therapist report of patient interventions . A survey of stroke unit re sources . METHODS Patients less than 14 days post-stroke from 5 metropolitan stroke units were observed over 2 consecutive weekdays at 10-minute intervals between 08.00 h and 17.00 h. Physical activity , location and person(s ) present were ascertained at each observation . Therapists completed treatment records . Senior staff completed stroke unit surveys . RESULTS Patients after stroke ( n=58 ) were with therapists 5.2 % of the observed day . Few patients ( 17.1 % ) received daily therapy by more than one therapist . When patients received therapy , average session times were 24 minutes of physiotherapy , 23 minutes of occupational therapy and 33 minutes of speech pathology . The more time that family members were present , the longer the treatment time . Four to 11 min of upper-limb therapy was provided . Muscle weakness and left hemiparesis were associated with less upper-limb activity . CONCLUSION These acute stroke care units were re source d according to recommended staff-patient ratios . Patients received little therapy and had low levels of physical activity", "Background and Purpose — One way that stroke units may improve outcome is by reducing complications of immobility through early mobilization ; however , this intervention needs testing . The purpose of this study was to determine the physical activity patterns of stroke patients managed within acute stroke units as a first step in developing an early mobilization protocol . Methods — We recruited 64 patients within 14 days after stroke from 5 metropolitan stroke units and observed them for 2 consecutive days at 10-minute intervals between the hours of 8 am and 5 pm . At each observation , we ascertained physical activity , location , and other person(s ) present . Therapists recorded therapy details . Results — The 58 patients who completed the study had a mean age of 71.3 years . Stroke severity ranged from mild ( National Institutes of Health Stroke Scale score , 1 ) to severe ( score , 27 ) , and mean time after stroke at observation was 5.6 days ( range , 0 to 13 days ) . Only 9 patients were restricted to bed . During the therapeutic day , patients spent > 50 % resting in bed , 28 % sitting out of bed , and only 13 % engaged in activities with the potential to prevent complications and improve recovery of mobility . Patients were alone > 60 % of the time . Conclusions — This is the first multicenter study of physical activity early after stroke . We believe the next step is to conduct a r and omized controlled trial to evaluate the effect of increased levels of physical activity early after stroke compared with current st and ards of care", "Background and Purpose — In prehension tasks with objects placed within arm ’s reach , patients with hemiparesis caused by stroke use excessive trunk movement to compensate for arm motor impairments . Compensatory trunk movements may improve motor function in the short term but may limit arm recovery in the long term . Previous studies showed that restriction of trunk movements during reach-to-grasp movements results in immediate increases in active arm joint ranges and improvement in interjoint coordination . To evaluate the potential of this technique as a therapeutic intervention , we compared the effects of short-term reach-to-grasp training ( 60-trial training session ) with and without physical trunk restraint on arm movement patterns in patients with chronic hemiparesis . Methods — A total of 28 patients with hemiparesis were assigned to 2 groups : 1 group practice d reach-to-grasp movements during which compensatory movement of the trunk was prevented by a harness ( trunk restraint ) , and the second group practice d the same task while verbally instructed not to move the trunk ( control ) . Kinematics of reaching and grasping an object placed within arm ’s length were recorded before , immediately after , and 24 hours after training . Results — The trunk restraint group used more elbow extension , less anterior trunk displacement , and had better interjoint coordination than the control group after training , and range of motion was maintained 24 hours later in only the trunk restraint group . Conclusions — Restriction of compensatory trunk movements during practice may lead to greater improvements in reach-to-grasp movements in patients with chronic stroke than practice alone , and longer-term effects of this intervention should be evaluated", "OBJECTIVE To evaluate the relationship between rehabilitation team functioning and stroke patient outcomes . DESIGN Prospect i ve observational study . SETTING Veterans Administration ( VA ) inpatient and subacute rehabilitation units . PARTICIPANTS Forty-six VA rehabilitation teams , including 530 rehabilitation team members from 6 disciplines ( medicine , nursing , social work , physical therapy , occupational therapy , speech language pathology ) and 1688 stroke patients treated by the teams . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Ten scales assessing team member perceptions of team functioning ( communication , perceived effectiveness , physician involvement , physician support , teamness , utility of quality information , innovation , interprofessional relationships , order and organization , task orientation ) and 3 primary patient outcome variables-functional improvement , discharge home , and length of rehabilitation stay ( LOS ) . RESULTS Three of the 10 measures of team functioning were significantly associated with patient functional improvement ( P task orientation , order and organization , and utility of quality information . One measure of team functioning-effectiveness-was significantly associated with LOS ( P discharge destination . Aspects of team functioning that were important to outcomes differed depending on the outcome of interests . Efforts directed toward improving team activities and relationships , including collaborative planning and problem solving and the use of feedback information , may enhance rehabilitation treatment effectiveness . CONCLUSIONS Characteristics of team functioning predict selected rehabilitation outcomes", "Background and Purpose — Current theories of motor control in rehabilitation focus on how the nervous system responds to many types of external and internal constraints to execute motor behavior to accomplish a task . However , the dynamic interplay between these 2 constraints remains unclear . This study examined the impact of some aspects of internal and external constraints on motor performance in persons with stroke . Methods — Twenty-seven persons with stroke used the uninvolved arms to perform an upper-extremity reaching task under 4 experimental conditions , formed by the crossing of functional goals and personal preferences . For the higher level of a functional goal , subjects took a drink from a can of beverage . For the lower level of a functional goal , subjects brought the can to the mouth without drinking . The level of personal preferences was determined , by interview , by the degree of predilection for particular beverages . Results — Significant and large effects of functional goals and personal preference were found in the variables of movement time and reaction time . However , the data trend of the 4 testing conditions varied according to presence of visuospatial neglect and side of lesion . Conclusions — Offering choices for the treatment activities and incorporating functional goals to therapeutic tasks might enhance response rate or movement efficiency , depending on the side of the lesion and presence of visuospatial neglect . The findings suggest that the consideration of the neglect phenomenon is a necessity when rehabilitative treatment planning incorporates constraint factors", "Objective : To evaluate the efficacy of a task-orientated intervention in enhancing competence in walking in people with stroke . Design : Two-centre observer-blinded stratified block-r and omized controlled trial . Setting : General community . Subjects : Between May 2000 and February 2003 , 91 individuals with a residual walking deficit within one year of a first or recurrent stroke consented to participate . Interventions : The experimental intervention comprised 10 functional tasks design ed to strengthen the lower extremities and enhance walking balance , speed and distance . The control intervention involved the practice of upper extremity activities . Subjects in both groups attended sessions three times a week for six weeks . Main measures : Six-minute walk test ( SMWT ) , 5-m walk ( comfortable and maximum pace ) , Berg Balance Scale , timed ‘ up and go ’ . Results : At baseline , subjects in the experimental ( n = 44 ) and control ( n = 47 ) groups walked an average distance of 209 m ( SD = 126 ) and 204 m ( SD = 131 ) , respectively , on the SMWT . Mean improvements of 40 m ( SD = 72 ) , and 5 m ( SD = 66 ) were observed following the experimental and control interventions , respectively . The between-group difference was 35 m ( 95 % confidence interval ( CI ) 7 , 64 ) . Significant between-group effects of 0.21 m/s ( 95 % CI 0.12 , 0.30 ) and of 0.11 m/s ( 95 % CI 0.03 , 0.19 ) in maximum and comfortable walking speed , respectively , were observed . People with a mild , moderate or severe walking deficit at baseline improved an average of 36 ( SD = 96 ) , 55 ( SD = 56 ) and 18 m ( SD = 23 ) , respectively , in SMWT performance following the experimental intervention . Conclusions : Study findings support the efficacy of a task-orientated intervention in enhancing walking distance and speed in the first year post stroke , particularly in people with moderate walking deficits", "Background and Purpose — Task-specific training improves functional outcomes after stroke . However , gains may be accompanied by increases in movements compensating for motor impairments . We hypothesized that restriction of compensatory trunk movements may encourage recovery of premorbid movement patterns leading to better functional outcomes . The goal was to determine whether task-specific training with trunk-restraint ( TR ) produces greater improvements in arm impairment and function than training without TR in patients with chronic hemiparesis . Methods — Double-blind r and omized control trial of a therapist-supervised home program ( 3 times per week , 5 weeks ) in 30 patients with chronic hemiparesis stratified by arm impairment level ( Fugl-Meyer ) was performed . Intervention group ( TR group ) received progressive object-related reach-to-grasp training with prevention of trunk movements . Control group ( C ) practice d tasks without TR . Main outcome measures were upper limb impairment ( Fugl-Meyer Arm Section ) and function ( TEMPA ) and movement kinematics ( trunk displacement , elbow extension ; Optotrak , 10 trials ) of a reach-to-grasp movement . Evaluations were repeated before , immediately after , and 1 month postintervention by blind evaluators . Results — TR training led to greater improvements in impairment and function compared with C. Improvements were accompanied by increased active joint range and were greater in initially more severe patients . In these patients , TR decreased trunk movement and increased elbow extension , whereas C had opposite effects ( increased compensatory movements ) . In TR , changes in arm function were correlated with changes in arm and trunk kinematics . Conclusions — Treatment should be tailored to arm impairment severity with particular attention to controlling excessive trunk movements if the goal is to improve arm movement quality and function", "Systematic review s provide the best evidence on the effectiveness of healthcare interventions including quality improvement strategies . The methods of systematic review of individual patient r and omised trials of healthcare interventions are well developed . We discuss method ological and practice issues that need to be considered when undertaking systematic review s of quality improvement strategies including developing a review protocol , identifying and screening evidence sources , quality assessment and data abstract ion , analytical methods , reporting systematic review s , and appraising systematic review s. This paper builds on our experiences within the Cochrane Effective Practice and Organisation of Care ( EPOC ) review group", "OBJECTIVES To evaluate the efficacy of a task-oriented walking intervention in improving balance self-efficacy in persons with stroke and to determine whether effects were task-specific , influenced by baseline level of self-efficacy and associated with changes in walking and balance capacity . DESIGN Secondary analysis of a two-center , observer-blinded , r and omized , controlled trial . SETTING General community . PARTICIPANTS Ninety-one individuals with a residual walking deficit within 1 year of a first or recurrent stroke . INTERVENTION Task-oriented interventions targeting walking or upper extremity ( UE ) function were provided three times a week for 6 weeks . MEASUREMENTS Activities-specific Balance Confidence Scale , Six-Minute Walk Test , 5-m walk , Berg Balance Scale , and Timed \" Up and Go \" administered at baseline and postintervention . RESULTS The walking intervention was associated with a significantly greater average proportional change in balance self-efficacy than the UE intervention . Treatment effects were largest in persons with low self-efficacy at baseline and for activities relating to tasks practice d. In the walking group , change in balance self-efficacy correlated with change in functional walking capacity ( correlation coefficient=0.45 , 95 % confidence interval=0.16 - 0.68 ) . Results of multivariable modeling suggested effect modification by the baseline level of depressive symptoms and a prognostic influence of age , sex , comorbidity , time poststroke , and functional mobility on change in self-efficacy . CONCLUSION Task-oriented walking retraining enhances balance self-efficacy in community-dwelling individuals with chronic stroke . Benefits may be partially the result of improvement in walking capacity . The influence of baseline level of self-efficacy , depressive symptoms , and prognostic variables on treatment effects are of clinical importance and must be verified in future studies", "Background and Purpose The purpose of this study was to determine the efficacy of a reimbursable , outpatient modified constraint-induced therapy ( mCIT ) protocol administered to subjects with chronic stroke who initially exhibited minimal movement ability in their affected wrists and fingers . Subjects The subjects were 4 individuals who had experienced a stroke more than 1 year prior to study entry ( mean age [±SD]=60.25±1.98 years , mean time since stroke=37.5±23.2 months ) . Method A multiple-baseline , preintervention-postintervention , single-blinded case series design was used . The intervention consisted of structured , ½-hour therapy sessions emphasizing affected arm use in valued activities , occurring 3 times per week for 10 weeks . Subjects ’ less affected arms also were restrained 5 days per week for 5 hours per day during the same 10-week period . The main outcome measures were the Action Research Arm Test ( ARAT ) , the Motor Activity Log ( MAL ) , and the Fugl-Meyer Assessment of Motor Recovery ( FM ) . Results The subjects exhibited improvements in use of the more affected arm ( + 1.9 , + 1.8 , + 1.7 , and + 2.3 for subjects 1 through 4 , respectively ) and in quality of movement ( + 1.5 , + 2.1 , + 1.63 , and + 1.9 for subjects 1 through 4 , respectively ) , as measured by the MAL . They also exhibited reduced impairment , as measured by the FM ( + 5.0 , + 6.5 , + 5.5 , and + 5.0 for subjects 1 through 4 , respectively ) , and increased fine motor skill movement , as measured by the ARAT ( + 7.5 , + 7.0 , + 7.0 , and + 5.5 for subjects 1 through 4 , respectively ) . Discussion and Conclusion The findings demonstrated that mCIT participation was efficacious because it led to increased use of the affected arm and of function and to increased ability to perform valued activities . The subjects reported some new ability to perform some valued activities . These outcomes are significant because few therapies are believed to effectively increase use of the affected arm and function in this population", "Background and Purpose — Outcome after first stroke varies significantly across Europe . This study was design ed to compare motor and functional recovery after stroke between four European rehabilitation centers . Methods — Consecutive stroke patients ( 532 patients ) were recruited . They were assessed on admission and at 2 , 4 , and 6 months after stroke with the Barthel Index , Rivermead Motor Assessment of Gross Function , Rivermead Motor Assessment of Leg/Trunk , Rivermead Motor Assessment of Arm , and Nottingham Extended Activities of Daily Living ( except on admission ) . Data were analyzed using r and om effects ordinal logistic models adjusting for case-mix and multiple testing . Results — Patients in the UK center were more likely to stay in lower Rivermead Motor Assessment of Gross Function classes compared with patients in the German center ( & Dgr;OR , 2.4 ; 95 % CI , 1.3 to 4.3 ) . In the Swiss center , patients were less likely to stay in lower Nottingham Extended Activities of Daily Living classes compared with patients in the UK center ( & Dgr;OR , 0.7 ; 95 % CI , 0.5 to 0.9 ) . The latter were less likely to stay in lower Barthel Index classes compared with the patients in the German center ( & Dgr;OR , 0.6 ; 95%CI , 0.4 to 0.8 ) . Recovery patterns of Rivermead Motor Assessment of Leg/Trunk and Rivermead Motor Assessment of Arm were not significantly different between centers . Conclusions — Gross motor and functional recovery were better in the German and Swiss centers compared with the UK center , respectively . Personal self-care recovery was better in the UK compared with the German center . Previous studies in the same centers indicated that German and Swiss patients received more therapy per day . This was not the result of more staff but of a more efficient use of human re sources . This study indicates potential for improving rehabilitation outcomes in the UK and Belgian centers", "OBJECTIVES To determine the effect of two different community-based group exercise programs on functional balance , mobility , postural reflexes , and falls in older adults with chronic stroke . DESIGN A r and omized , clinical trial . SETTING Community center . PARTICIPANTS Sixty-one community-dwelling older adults with chronic stroke . INTERVENTION Participants were r and omly assigned to an agility ( n=30 ) or stretching/weight-shifting ( n=31 ) exercise group . Both groups exercised three times a week for 10 weeks . MEASUREMENTS Participants were assessed before , immediately after , and 1 month after the intervention for Berg Balance , Timed Up and Go , step reaction time , Activities-specific Balance Confidence , and Nottingham Health Profile . Testing of st and ing postural reflexes and induced falls evoked by a translating platform was also performed . In addition , falls in the community were tracked for 1 year from the start of the interventions . RESULTS Although exercise led to improvements in all clinical outcome measures for both groups , the agility group demonstrated greater improvement in step reaction time and paretic rectus femoris postural reflex onset latency than the stretching/weight-shifting group . In addition , the agility group experienced fewer induced falls on the platform . CONCLUSION Group exercise programs that include agility or stretching/weight shifting exercises improve postural reflexes , functional balance , and mobility and may lead to a reduction of falls in older adults with stroke", "Background and Purpose — Differences exist between European countries in the proportion of patients who die or become dependent after stroke . The aim of the present study was to identify differences in the use of time by stroke patients in 4 rehabilitation centers in 4 European countries . Methods — In each of the 4 centers , 60 r and omly selected stroke patients were observed at 10-minute intervals using behavioral mapping . Observations took place on 30 weekdays selected at r and om , on equal numbers of morning , afternoon , and evening sessions . A logistic generalized estimating equation model with correction for differences in case mix and multiple testing was used for the analysis . Results — Overall time available from different professions was the highest in the United Kingdom , but patients in the United Kingdom spent on average only 1 hour per day in therapy . This was significantly less than patients in Belgium and Germany , who spent ≈2 hours , and patients in Switzerl and who spent ≈3 hours per day in therapy . In all centers , patients spent less than half their time in interactions and > 72 % of the time in nontherapeutic activities . Conclusions — Important differences in the use of time were established , which appeared dependent on management decisions rather than the number of staff available . Patients in the Swiss and German centers spent more time in therapy , possibly because of the structured organization of rehabilitation . Further studies will verify whether this has an effect on outcome", "Background and Purpose — Mental practice ( MP ) of a particular motor skill has repeatedly been shown to activate the same musculature and neural areas as physical practice of the skill . Pilot study results suggest that a rehabilitation program incorporating MP of valued motor skills in chronic stroke patients provides sufficient repetitive practice to increase affected arm use and function . This Phase 2 study compared efficacy of a rehabilitation program incorporating MP of specific arm movements to a placebo condition using r and omized controlled methods and an appropriate sample size . Method — Thirty-two chronic stroke patients ( mean=3.6 years ) with moderate motor deficits received 30-minute therapy sessions occurring 2 days/week for 6 weeks , and emphasizing activities of daily living . Subjects r and omly assigned to the experimental condition also received 30-minute MP sessions provided directly after therapy requiring daily MP of the activities of daily living ; subjects assigned to the control group received the same amount of therapist interaction as the experimental group , and a sham intervention directly after therapy , consisting of relaxation . Outcomes were evaluated by a blinded rater using the Action Research Arm test and the upper extremity section of the Fugl-Meyer Assessment . Results — No pre-existing group differences were found on any demographic variable or movement scale . Subjects receiving MP showed significant reductions in affected arm impairment and significant increases in daily arm function ( both at the P perform valued activities . Conclusions — The results support the efficacy of programs incorporating mental practice for rehabilitating affected arm motor function in patients with chronic stroke . These changes are clinical ly significant", "The purpose of this study was to investigate whether additional practice of either upper limb or mobility tasks improved functional outcome during inpatient stroke rehabilitation . This prospect i ve , r and omised , single blind clinical trial recruited 30 stroke subjects into either an Upper Limb or a Mobility Group . All subjects received their usual rehabilitation and an additional session of task-related practice using a circuit class format . Independent assessors , blinded to group allocation , tested all subjects . Outcome measures used were three items of the Jebsen Taylor H and Function Test ( JTHFT ) , two arm items of the Motor Assessment Scale ( MAS ) , and three mobility measures , the Timed Up and Go Test ( TUGT ) , Step Test , and Six Minute Walk Test ( 6MWT ) . Both groups improved significantly between pre- and post-tests on all of the mobility measures , however only the Upper Limb Group made a significant improvement on the JTHFT and MAS upper arm items . Following four weeks training , the Mobility Group had better locomotor ability than the Upper Limb Group ( between-group differences in the 6MWT of 116.4 m , 95 % CI 31.4 to 201.3 m , Step Test 2.6 repetitions , 95 % CI -1.0 to 6.2 repetitions , and TUGT -7.6 sec , 95 % CI -15.5 to 0.2 sec ) . The JTHFT dexterity scores in the Upper Limb Group were 6.5 sec ( 95 % CI -7.4 to 20.4 sec ) faster than the Mobility Group . Our findings support the use of additional task-related practice during inpatient stroke rehabilitation . The circuit class format was a practical and effective means to provide supervised additional practice that led to significant and meaningful functional gains", "Two important components of Constraint-Induced Movement therapy are thought to be intense training of the more-impaired arm and physical restraint of the less-impaired arm . This preliminary study examined the effects of type of training ( task- practice , shaping ) and restraint ( sling , half-glove , no restraint ) on treatment outcomes . Seventeen individuals at least 1-year post-stroke with mild/moderate upper extremity motor deficit were consecutively assigned to Sling and Task- practice , Sling and Shaping , Half-glove and Shaping , and Shaping Only groups . Task- practice involved repetitive more-impaired arm training on functional tasks for 6 hr/day for 10 consecutive weekdays . Shaping differed from task- practice in that task dem and s were progressively increased and immediate performance feedback was provided frequently and systematic ally . \" Sling \" groups placed the less-impaired arm in a resting h and -splint/sling assembly for most waking hours over the 2-week intervention , while the \" Half-glove \" group wore a modified gardening glove as a reminder not to use the more affected arm in the life situation . There were no between-group differences in outcome at post-treatment , although two-years afterwards Sling & Task- practice and Half-glove & Shaping participants showed larger and smaller retention of gains , respectively , than those in the Sling & Shaping group . Thus , long-term outcomes may have been affected by type of more-impaired arm motor training and less-impaired arm restraint . These variables , however , were confounded with between-group differences in training intensity , limiting confidence in this conclusion", "BACKGROUND AND PURPOSE After stroke , the ability to balance in sitting is critical to independence . Although impairments in sitting balance are common , little is known about the effectiveness of rehabilitation strategies design ed to improve it . The purpose of this r and omized placebo-controlled study was to evaluate the effect of a 2-week task-related training program aim ed at increasing distance reached and the contribution of the affected lower leg to support and balance . METHODS Twenty subjects at least 1 year after stroke were r and omized into an experimental or control group . The experimental group participated in a st and ardized training program involving practice of reaching beyond arm 's length . The control group received sham training involving completion of cognitive-manipulative tasks within arm 's length . Performance of reaching in sitting was measured before and after training using electromyography , videotaping , and two force plates . Variables tested were movement time , distance reached , vertical ground reaction forces through the feet , and muscle activity . Subjects were also tested on sit-to-st and , walking , and cognitive tasks . Nineteen subjects completed the study . RESULTS After training , experimental subjects were able to reach faster and further , increase load through the affected foot , and increase activation of affected leg muscles compared with the control group ( P sit-to-st and . The control group did not improve in reaching or sit-to-st and . Neither group improved in walking . CONCLUSIONS This study provides strong evidence of the efficacy of task-related motor training in improving the ability to balance during seated reaching activities after stroke", "OBJECTIVE To evaluate the immediate and retention effects of a 4-week training program on the performance of locomotor-related tasks in chronic stroke . DESIGN R and omized , controlled pilot study with 2-month follow-up . SETTING Rehabilitation center . SUBJECTS A convenience sample consisting of 12 chronic stroke subjects was used . Subjects were r and omly assigned to the experimental or the control group . Three subjects withdrew from the study . INTERVENTION Both experimental and control groups participated in exercise classes three times a week for 4 weeks . The exercise class for the experimental group focused on strengthening the affected lower limb and practicing functional tasks involving the lower limbs , while the control group practice d upper-limb tasks . MAIN OUTCOME MEASURES Lower-limb function was evaluated by measuring walking speed and endurance , peak vertical ground reaction force through the affected foot during sit-to-st and , and the step test . RESULTS The experimental group demonstrated significant immediate and retained ( 2-month follow-up ) improvement ( p walking speed and endurance , force production through the affected leg during sit-to-st and , and the number of repetitions of the step test . CONCLUSION The pilot study provides evidence for the efficacy of a task-related circuit class at improving locomotor function in chronic stroke", "OBJECTIVE To evaluate the immediate and long-term effects of 2 upper-extremity rehabilitation approaches for stroke compared with st and ard care in participants stratified by stroke severity . DESIGN Nonblinded , r and omized controlled trial ( baseline , postintervention , 9mo ) design . SETTING Inpatient rehabilitation hospital and outpatient clinic . PARTICIPANTS Sixty-four patients with recent stroke admitted for inpatient rehabilitation were r and omized within severity strata ( Orpington Prognostic Scale ) into 1 of 3 intervention groups . Forty-four patients completed the 9-month follow-up . INTERVENTIONS St and ard care ( SC ) , functional task practice ( FT ) , and strength training ( ST ) . The FT and ST groups received 20 additional hours of upper-extremity therapy beyond st and ard care distributed over a 4- to 6-week period . MAIN OUTCOME MEASURES Performance measures of impairment ( Fugl-Meyer Assessment ) , strength ( isometric torque ) , and function ( Functional Test of the Hemiparetic Upper Extremity [ FTHUE ] ) . RESULTS Compared with SC participants , those in the FT and ST groups had significantly greater increases in Fugl-Meyer motor scores ( P=.04 ) and isometric torque ( P=.02 ) posttreatment . Treatment benefit was primarily in the less severe participants , where improvement in FT and ST group Fugl-Meyer motor scores more than doubled that of the SC group . Similar results were found for the FTHEU and isometric torque . During the long term , at 9 months , the less severe FT group continued to make gains in isometric muscle torque , significantly exceeding those of the ST group ( P<.05 ) . CONCLUSIONS Task specificity and stroke severity are important factors for rehabilitation of arm use in acute stroke . Twenty hours of upper extremity-specific therapy over 4 to 6 weeks significantly affected functional outcomes . The immediate benefits of a functional task approach were similar to those of a resistance-strength approach , however , the former was more beneficial in the long-term", "Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists", "OBJECTIVE To compare body weight-supported exercise on a gait trainer with walking exercise overground . DESIGN R and omized controlled trial . SETTING Rehabilitation hospital . PARTICIPANTS Forty-five ambulatory patients with chronic stroke . INTERVENTIONS Patients were r and omized to 3 groups : ( 1 ) gait trainer exercise with functional electric stimulation ( GTstim ) , ( 2 ) gait trainer exercise without stimulation ( GT ) , and ( 3 ) walking overground ( WALK ) . All patients practice d gait for 15 sessions during 3 weeks ( each session , 20 min ) , and they received additional physiotherapy 55 minutes daily . MAIN OUTCOME MEASURES Ten-meter walk test ( 10MWT ) , six-minute walk test ( 6MWT ) , lower-limb spasticity and muscle force , postural sway tests , Modified Motor Assessment Scale ( MMAS ) , and FIM instrument scores were recorded before , during , and after the rehabilitation and at 6 months follow-up . RESULTS The mean walking distance using the gait trainer was 6900+/-1200 m in the GTstim group and 6500+/-1700 m in GT group . In the WALK group , the distance was 4800+/-2800 m , which was less than the walking distance obtained in the GTstim group ( P=.027 ) . The body-weight support was individually reduced from 30 % to 9 % of the body weight over the course of the program . In the pooled 45 patients , the 10MWT ( P 6MWT ( P MMAS ( P dynamic balance test time ( P test trip ( P=.005 ) scores improved ; however , no differences were found between the groups . CONCLUSIONS Both the body weight-supported training and walking exercise training programs result ed in faster gait after the intensive rehabilitation program . Patients ' motor performance remained improved at the follow-up", "Objective : To determine ( 1 ) the most effective of three treatment approaches to retrain seated weight distribution long-term after stroke and ( 2 ) whether improvements could be generalized to weight distribution in st and ing . Setting : Inpatient rehabilitation unit . Design : Forty asymmetrical acute stroke subjects were r and omly allocated to one of four groups in this pilot study . Changes in weight distribution were compared between the 10 subjects of each of three treatment groups ( task-specific reach , Bobath , or Balance Performance Monitor [ BPM ] feedback training ) and a no specific treatment control group . One week of measurement only was followed by two weeks of daily training sessions with the treatment to which the subject was r and omly allocated . Measurements were performed using the BPM daily before treatment sessions , two weeks after cessation of treatment and 12 weeks post study . Weight distribution was calculated in terms of mean balance ( percentage of total body weight ) or the mean of 300 balance points over a 30-s data run . Results : In the short term , the Bobath approach was the most effective treatment for retraining sitting symmetry after stroke ( p = 0.004 ) . Training with the BPM and no training were also significant ( p = 0.038 and p = 0.035 respectively ) and task-specific reach training failed to reach significance ( p = 0.26 ) . At 12 weeks post study 83 % of the BPM training group , 38 % of the task-specific reach group , 29 % of the Bobath group and 0 % of the untrained group were found to be distributing their weight to both sides . Some generalization of symmetry training in sitting to st and ing was noted in the BPM training group which appeared to persist long term . Conclusions : Results should be treated with caution due to the small group sizes . However , these preliminary endings suggest that it might be possible to restore postural symmetry in sitting in the early stages of rehabilitation with therapy that focuses on creating an awareness of body position", "This trial compares the effects of task-oriented physical therapy ( PT ) provided with and without the use of rehabilitation technology on locomotor recovery in 63 persons with subacute stroke . Participants in the experimental ( EXP ) group used a treadmill , a Kinetron isokinetic exerciser , and a limb-load monitor , whereas those in the control ( CTL ) group did not while engaging in PT 1 h per day , 5 days per week for 2 months . Locomotor recovery was assessed by clinical ( gait speed , Fugl Meyer motor leg and arm subscores , the Balance Scale , the Timed Up and Go , and the Barthel ambulation subscore ) and laboratory outcomes ( gait kinematics and kinetics ) pre- and posttherapy and 3 months later . Within groups , gait speed ( P 0.05 ) . When the groups were pooled , the increase in gait speed was associated ( r = 0.52 , P = 0.003 ) with an increase in ankle power generation of the affected leg . The results demonstrate that the efficacy of the task-oriented approach is not dependent on rehabilitation technology", "Objective : To investigate the effect of early cycling training on balance and motor abilities of stroke patients in their subacute stage . Design : R and omized clinical trial . Setting : Inpatient rehabilitation . Subjects : Twenty-four patients who had had a first stroke were r and omly assigned to a cycling training group ( n = 10 ) or to a control ( n = 14 ) group . Intervention : All subjects received their usual rehabilitation programme ; the cycling training group received in addition a daily session of leg cycle ergometer , lasting three weeks . Both groups were followed for six weeks . Main outcome measurements : Balance was assessed using the Postural Assessment Scale for Stroke Patients ( PASS ) and the st and ing balance test . The motor function of the lower extremity was also assessed by the Fugl-Meyer Assessment ( FMA ) . Results : In the within-group comparison , both the exercise group and the control group had improved significantly ( P B=0.01 ) with time with respect to PASS total ( exercise group 18.79=2.8 to 31.19=2.2 , control group 18.19=3.2 to 26.49=3.8 ) and PASS subscores , as well as the FMA score ( exercise group 17.29=7.5 to 29.19=5.9 , control group 16.69=6.4 to 22.19=6.8 ) . In addition there was a significant group = time interaction effect , with exercise group patients demonstrating better performance in both the total PASS score and PASS subscores and FMA score relative to the control patients ( P B=0.01 ) . Conclusions : These preliminary findings suggest that stroke patients in the subacute stage can improve their motor and balance abilities after an early short duration of cycling training", "OBJECTIVE To explore how repetitive passive-active movement training effects upper limb motor function and cortical activation in patients with stroke . DESIGN Single-group treatment trial with baseline comparisons . PATIENTS Ten chronic patients with stroke with paresis of the upper limb . METHODS Assessment s were performed during a 4-week baseline period before and once after 4 weeks of training using the Motor Assessment Scale of the upper limb , Nine Hole Peg Test , goniometer for range of movement and the modified Ashworth scale for muscle tone . Two patients underwent functional magnetic resonance imaging pre- and post-training . The treatment consisted of daily sessions of repeated functional reaching and grasping movements guided passively and attempted actively during 4 weeks . RESULTS The group improved in range of motion and Motor Assessment Scale scores . Subjects reported improvements in a variety of daily tasks requiring the use of the affected upper limb . Increases in cortical activation in prefrontal and sensorimotor areas were observed in parallel with improvements of upper limb motor function in the 2 patients scanned . CONCLUSION The 4-week training programme improved h and motor function and ability . Cortical activation on functional magnetic resonance imaging changed in parallel suggesting reorganization of areas related to movements of the paretic limb", "OBJECTIVE To examine the benefits of modified constraint-induced movement therapy ( mCIMT ) on motor function , daily function , and health-related quality of life ( HRQOL ) in elderly stroke survivors . DESIGN Two-group r and omized controlled trial , with pretreatment and posttreatment measures . SETTING Rehabilitation clinics . PARTICIPANTS Twenty-six elderly stroke patients ( mean age , 72 y ) with 0.5 to 31 months postonset of a first-ever cerebrovascular accident . INTERVENTIONS Twenty-six patients received either mCIMT ( restraint of the unaffected limb combined with intensive training of the affected limb ) or traditional rehabilitation for a period of 3 weeks . MAIN OUTCOME MEASURES Outcome measures included the Fugl-Meyer Assessment ( FMA ) , FIM instrument , Motor Activity Log ( MAL ) , and Stroke Impact Scale ( SIS ) . The FMA evaluated the severity of motor impairment ; the FIM instrument and MAL reported daily function ; and the SIS detected HRQOL . RESULTS The mCIMT group exhibited significantly greater improvements in motor function , daily function , and the physical domain of HRQOL than the traditional rehabilitation group . Patients in the mCIMT group perceived significantly greater percent of recovery after treatment than patients in the traditional rehabilitation group . CONCLUSIONS These findings suggest mCIMT is a promising intervention for improving motor function , daily function , and physical aspects of HRQOL in elderly patients with stroke . The mCIMT was well tolerated by the elderly patients even though it is a rigorous training program", "Background : Neurodevelopmental treatment ( NDT ) is a rehabilitation approach increasingly used in the care of stroke patients , although no evidence has been provided for its efficacy . Objective : To investigate the effects of NDT on the functional status and quality of life ( QoL ) of patients with stroke during one year after stroke onset . Methods : 324 consecutive patients with stroke from 12 Dutch hospitals were included in a prospect i ve , non-r and omised , parallel group study . In the experimental group ( n = 223 ) , nurses and physiotherapists from six neurological wards used the NDT approach , while conventional treatment was used in six control wards ( n = 101 ) . Functional status was assessed by the Barthel index . Primary outcome was “ poor outcome ” , defined as Barthel index assessed with the 30 item version of the sickness impact profile ( SA-SIP30 ) and the visual analogue scale . Results : At 12 months , 59 patients ( 27 % ) in the NDT group and 24 ( 24 % ) in the non-NDT group had poor outcome ( corresponding adjusted odds ratio = 1.7 ( 95 % confidence interval , 0.8 to 3.5 ) ) . At discharge the adjusted odds ratio was 0.8 ( 0.4 to 1.5 ) and after six months it was 1.6 ( 0.8 to 3.2 ) . Adjusted mean differences in the two QoL measures showed no significant differences between the study groups at six or 12 months after stroke onset . Conclusions : The NDT approach was not found effective in the care of stroke patients in the hospital setting . Health care professionals need to reconsider the use of this approach", "Objective : To compare the effect of walking training on a treadmill with body weight support ( BWS ) and walking training on the ground at an early stage of rehabilitation in patients with hemiparesis after stroke . Design : R and omized controlled experimental study . Setting : Multicentre design ; three departments of rehabilitation medicine . Subjects : Seventy-three consecutive first stroke patients admitted to a rehabilitation clinic were r and omized into a treatment group and a control group . Interventions : The treatment group received walking training on a treadmill with BWS for 30 minutes , 5 days a week . The control group received walking training according to the Motor Relearning Programme ( MRP ) on the ground for 30 minutes 5 days a week , not including treadmill training . During the time in the rehabilitation department ( about two months ) , all patients in the study also received professional stroke rehabilitation besides the walking training in the two groups . Main outcome measures : Functional Independence Measure ( FIM ) , walking velocity for 10 m , Functional Ambulation Classification ( FAC ) , Fugl-Meyer Stroke Assessment and Berg 's Balance Scale . The assessment s were performed at admission , at discharge and at 10-month follow-up . Results : There were no statistically significant differences between the groups at discharge or at the 10-month follow-up with regard to FIM , walking velocity , FAC , Fugl-Meyer Stroke Assessment , and Berg 's Balance Scale . Patients in both groups improved in these variables from admission to the 10-month follow-up . Conclusions : Treadmill training with BWS at an early stage of rehabilitation after stroke is a comparable choice to walking training on the ground", "OBJECTIVE To evaluate the effectiveness of 2 rehabilitative approaches for improving paretic limb reaching by chronic stroke subjects . DESIGN Pre- and posttest reaching to targets ipsilateral , midline , and contralateral to the impaired side . SETTING Training in subjects ' homes ; testing in a laboratory setting . PARTICIPANTS Twelve poststroke volunteers were matched using the Motor Assessment Scale ( MAS ) and then were r and omly assigned to 1 of 2 training conditions . Subjects were subsequently categorized as at a high or low functional level , using the reaching pretest movement time scores . INTERVENTIONS Training ( trunk unrestrained ) using the paretic limb was 4 weeks ( 12 sessions ) . Task-related training ( TRT ) involved reaching to objects placed across the workspace . Progressive resistive exercise ( PRE ) involved whole-arm pulling against resistive therapeutic tubing in planes and distances similar to that in TRT . Main outcome measures Kinematic analysis of arm trajectory and trunk motion using the Peak Performance System , as well as scores on the MAS and the Rivermead Motor Assessment ( RMA ) . RESULTS For low-level groups , TRT result ed in increased substitutive trunk use at the target ipsilateral to the moving arm , and for midline and contralateral targets after PRE . Only low-level , TRT subjects straightened h and paths , which suggested better coordination of elbow-shoulder motion , and improved on the RMA . High-level subjects decreased trunk use at ipsilateral target after PRE , which was not observed after TRT . No significant differences between training conditions were found for other kinematic variables . CONCLUSIONS Training benefits appear to depend on initial level of functioning . Although compensatory trunk use was evident , low-level subjects seemed to benefit most from TRT . High-level subjects , whose kinematics showed fairly normal movement organization , demonstrated less compensatory movement after PRE", "Objectives : To evaluate a training programme aim ed at improving lateral weight transference in patients following acute stroke to determine main treatment effects , if any , to inform the design of future studies . Design : A single-blind r and omized controlled trial . Setting : The Stroke Unit at The James Cook University Hospital , Middlesbrough , UK . Subjects : Thirty-five patients with an acute stroke . Interventions : All subjects received their usual care , including physiotherapy . The treatment group ( n / 17 ) received 12 additional therapy sessions ( over four weeks ) comprising exercises aim ed at improving lateral weight transference in sitting delivered by trained physiotherapy assistants . Main outcome measures : Measures of dynamic reaching , sitting and st and ing , and static st and ing balance were undertaken by a blind independent observer . Results : Specific measures of weight displacement in st and ing and reaching , and timed st and ing up and sitting down did not detect any differences over time regardless of group . Neither were there any significant changes over time , except for sway during static st and ing ( p B=0.01 ) and time to return to their original position during dynamic reaching ( p / 0.01 ) . Conclusions : A training programme aim ed at improving lateral weight transference did not appear to enhance the rehabilitation of acute stroke patients . Improvements observed in postural control in st and ing and sitting may be attributable to usual care or natural recovery", "OBJECTIVES To examine the effects of a community-based group exercise program for older individuals with chronic stroke . DESIGN Prospect i ve , single-blind , r and omized , controlled intervention trial . SETTING Intervention was community-based . Data collection was performed in a research laboratory located in a rehabilitation hospital . PARTICIPANTS Sixty-three older individuals ( aged > or = 50 ) with chronic stroke ( poststroke duration > or = 1 year ) who were living in the community . INTERVENTION Participants were r and omized into intervention group ( n=32 ) or control group ( n=31 ) . The intervention group underwent a fitness and mobility exercise ( FAME ) program design ed to improve cardiorespiratory fitness , mobility , leg muscle strength , balance , and hip bone mineral density ( BMD ) ( 1-hour sessions , three sessions/week , for 19 weeks ) . The control group underwent a seated upper extremity program . MEASUREMENTS Cardiorespiratory fitness ( maximal oxygen consumption ) , mobility ( 6-minute walk test ) , leg muscle strength ( isometric knee extension ) , balance ( Berg Balance Scale ) , activity and participation ( Physical Activity Scale for Individuals with Physical Disabilities ) , and femoral neck BMD ( using dual-energy x-ray absorptiometry ) . RESULTS The intervention group had significantly more gains in cardiorespiratory fitness , mobility , and paretic leg muscle strength than controls . Femoral neck BMD of the paretic leg was maintained in the intervention group , whereas a significant decline of the same occurred in controls . There was no significant time-by-group interaction for balance , activity and participation , nonparetic leg muscle strength , or nonparetic femoral neck BMD . CONCLUSION The FAME program is feasible and beneficial for improving some of the secondary complications result ing from physical inactivity in older adults living with stroke . It may serve as a good model of a community-based fitness program for preventing secondary diseases in older adults living with chronic conditions", "OBJECTIVE To determine the role of symmetrical body-weight distribution training in preventing falls among patients with hemiplegic stroke . DESIGN A prospect i ve study using a st and ing biofeedback trainer . SETTING Hospital-based rehabilitation units . PATIENTS Fifty-four patients with hemiplegic stroke ( 30 in the training group , 24 in the control group ) . INTERVENTIONS Conventional stroke rehabilitation program , plus symmetrical st and ing training and repetitive sit-to-st and training , with a st and ing biofeedback trainer . Training effect was evaluated by assessing the sit-to-st and performance and comparing the occurrence of falls in the 2 groups at a 6-month follow-up . MAIN OUTCOME MEASURES Occurrence of falls , sit-to-st and performance , including body-weight distribution , rate of rise in force , and sway in center of pressure ( COP ) . RESULTS Significant improvement in sit-to-st and performance was found in patients in the training group . Body weight was distributed more symmetrically in both legs , with less mediolateral sway in the COP when rising and sitting down . The mean difference in body-weight distribution between the left and right legs while subjects were rising from a chair significantly decreased , from 49.5 % + /- 18.9 % to 38.6 % + /- 15.8 % of body weight ( BW ) ( p rate of rise in force while rising from a chair significantly increased , from 28.3 % + /- 13.5%BW/s to 53.6 % + /- 20.5%BW/s ( p fallen , compared with only 5 of 30 patients ( 16.7 % ) in the training group ( p sit-to-st and performance and , consequently , decrease the number of falls by stroke patients", "Purpose . The purpose of this study was to characterize the gait cycle of patients with hemiplegia before and after a period of outpatient physiotherapy based on the Bobath concept . Methods . Nine patients , at least 6 weeks post stroke and recently discharged from a stroke unit , were measured before and after a period of outpatient physiotherapy ( mean duration = 17.4 weeks ) . Therapy was documented using a treatment checklist for each patient . The primary outcome measures were a number of gait variables related to the therapists ' treatment hypothesis , recorded during the gait cycle using the CODA motion analysis system . Other secondary outcome measures were the Motor Assessment Scale , Modified Ashworth Scale , subtests of the Sodring Motor Evaluation Scale , the Step test , a 10-m walk test , the Barthel Index and the London H and icap Score . Results . Recovery of more normal gait patterns in the gait cycle ( using motion analysis ) did not occur . Significant changes in temporal parameters ( loading response , single support time ) for both legs , in one kinematic ( dorsiflexion during stance ) and one kinetic variable on the unaffected side ( hip flexor moment ) , and most of the clinical measures of impairment , activity and participation ( with the exception of the Modified Ashworth Scale and the 10-m walk ) were noted . Conclusions . Study findings did not support the hypothesis that the Bobath approach restored more normal movement patterns to the gait cycle . Further research is required to investigate the treatment techniques that are effective at improving walking ability in people after stroke", "AIM This paper reports an evaluation of a range-of-motion exercise programme aim ed at improving joint flexibility , activity function , perception of pain , and depressive symptoms in a sample of stroke survivors in long-term care facilities . BACKGROUND The benefits of physical rehabilitation for stroke survivors have been well established . There is , however , little empirical data on the effects of a simple nurse-led range-of-motion exercise programme in improving function for these people . METHOD A r and omized controlled trial was conducted in 1999 with 59 bedridden older stroke survivors in residential care . Participants were r and omly assigned to usual care or one of two intervention groups . The 4-week , twice-per-day , 6 days-per-week range-of-motion exercise protocol s were similar in both intervention groups , and consisted of full range-of-motion exercises of the upper and lower extremities . To test the effect of different degrees of staff involvement , in intervention group I , a Registered Nurse was present to supervise participants performing the exercises , while intervention group II involved a Registered Nurse physically assisting participants to achieve maximum range-of-motion within or beyond their present abilities . RESULTS Both intervention groups had statistically significant improvement in joint angles , activity function , perception of pain and depressive symptoms compared with the usual care group ( P joint angles in intervention group II were statistically significantly wider than in both the other groups ( P nurse-led range-of-motion exercise programme can generate positive effects in enhancing physical and psychological function of bedridden older people with stroke . Further studies are needed to investigate the long-term effects of the programme in maximizing function , reducing care utilization and enhancing quality of life for this population", "Objective : To find out if there were any differences in improvement and maintenance of motor function , activity of daily living and grip strength between patients with first-ever stroke receiving two different strategies of physical exercise during the first year after stroke . Design : A longitudinal r and omized controlled stratified trial . Setting : Rehabilitation institutions , community , patients ' homes and nursing homes . Subjects : Seventy-five male and female first-time-ever stroke patients : 35 in an intensive exercise group and 40 in a regular exercise group . Intervention : The intensive exercise group received physiotherapy with focus on intensive exercises in four periods during the first year after stroke . The regular exercise group patients were followed up according to their subjective needs during the corresponding year . Main outcome measures : Motor Assessment Scale , Barthel Index of Activities of Daily Living , and grip strength . Results : Both groups improved significantly up to six months when function stabilized . The groups did not differ significantly on any test occasions . The difference of improvement from admission to discharge was significant in favour of the intensive exercise group , in the Motor Assessment Scale total score ( intensive exercise group 7.5 ; regular exercise group 1.7 , P = 0.01 ) , and in the Barthel Index of Activities of Daily Living total score ( 17.4 versus 8.9 , P = 0.04 ) . Conclusion : Motor function , activities of daily living functions and grip strength improved initially and were maintained during the first year after stroke in all patients irrespective of exercise regime . This indicates the importance of motivation for regular exercise in the first year following stroke , achieved by regular check-ups", "Objective : To investigate the effect of perceptual learning exercises for hardness discrimination by the soles on st and ing balance in stroke patients with hemiplegia . Subjects : Twenty-eight subjects were r and omly assigned to an experimental or a control group and participated in a rehabilitation programme . Intervention : The experimental group received perceptual learning exercises on hardness discrimination using three different levels of hardness of a rubber sponge for 10 days . Main measures : Length , enveloped area and rectangular area of the parameter of postural sway were measured by a stabilometer on entry into the study and after 10 days . Results : Twenty-six subjects completed the study . Data indicate that more parameters indicating postural sway were significantly decreased in the experimental group than in the control group . Also , there was a significant difference between the groups in change scores ( pre-exercise minus postexercise ) of length and enveloped area . Conclusion : The plantar perception exercise used as a method in this study is considered to be effective as a supplemental exercise for st and ing balance . The possibility of clinical application using the hardness discrimination task with rubber as a balance exercise is therefore suggested", "Objective : To investigate whether early aerobic training has a beneficial effect on stroke patients ' independence in daily and social activities six months after the event . Design : R and omized clinical trial . Setting : Rehabilitation unit . Subjects : Ninety-two patients after a first stroke . Interventions : Forty-six patients participated in an eight-week programme of aerobic training , using a leg cycle ergometer . Main outcome measures : Frenchay Activities Index ( FAI ) measured twice , at entry to programme ( pre-event score ) and six months after the onset of the event . Results : Despite the significant improvement of study group patients ' functional abilities immediately after the intervention compared with controls , no significant difference was found in FAI mean score between groups six months post event . An interaction effect was noted between event severity , intervention and FAI total score . Mean FAI score declined significantly less in the less severely impaired study group patients . Conclusions : Early , moderately intense aerobic training has no direct impact on independence in daily and social activities as measured by FAI total score six months after a stroke", "OBJECTIVE To assess the effects of a community-based exercise program on motor recovery and functional abilities of the paretic upper extremity in persons with chronic stroke . DESIGN R and omized controlled trial . SETTING Rehabilitation research laboratory and a community hall . PARTICIPANTS A sample of 63 people ( > or = 50y ) with chronic deficits result ing from stroke ( onset > or = 1y ) . INTERVENTIONS The arm group underwent an exercise program design ed to improve upper-extremity function ( 1h/session , 3 sessions/wk for 19wk ) . The leg group underwent a lower-extremity exercise program . MAIN OUTCOME MEASURES The Wolf Motor Function Test ( WMFT ) , Fugl-Meyer Assessment ( FMA ) , h and -held dynamometry ( grip strength ) , and the Motor Activity Log . RESULTS Multivariate analysis showed a significant group by time interaction ( Wilks lambda=.726 , P=.017 ) , indicating that overall , the arm group had significantly more improvement than the leg group . Post hoc analysis demonstrated that gains in WMFT ( functional ability ) ( P=.001 ) and FMA ( P=.001 ) scores were significantly higher in the arm group . The amount of improvement was comparable to other novel treatment approaches such as constraint-induced movement therapy or robot-aided exercise training previously reported in chronic stroke . Participants with moderate arm impairment benefited more from the program . CONCLUSIONS The pilot study showed that a community-based exercise program can improve upper-extremity function in persons with chronic stroke . This outcome justifies a larger clinical trial to further assess efficacy and cost effectiveness", "QUESTION What is the effect of a sitting training protocol in people early after stroke on sitting ability and quality , and does it carry over to mobility ? DESIGN R and omised placebo-controlled trial with concealed allocation , assessor blinding and intention-to-treat analysis . PARTICIPANTS Twelve individuals who had a stroke less than three months previously and were able to sit unsupported . INTERVENTION The experimental group completed a 2-week sitting training protocol that involved practising reaching tasks beyond arm 's length . The control group completed a 2-week sham sitting training protocol that involved practising cognitive-manipulative tasks within arm 's length . OUTCOME MEASURES The primary outcome was sitting ability ( maximum reach distance ) . Secondary outcomes were sitting quality ( reach movement time and peak vertical force through affected foot during reaching ) and carry over to mobility ( peak vertical force through affected foot during st and ing up and walking speed during 10 m Walk Test ) . Outcome measures were taken before and after training and six months later . RESULTS After 2 weeks ' training , the experimental group had increased their maximum reach distance by 0.17 m ( 95 % CI 0.12 to 0.21 ) , decreased their movement time by 0.5 s ( 95 % CI -0.8 to -0.2 ) , increased their peak vertical force through the affected foot during reaching by 13 % of body weight ( 95 % CI 6 to 20 ) and increased their peak vertical force through the affected foot during st and ing up by 21 % of body weight ( 95 % CI 14 to 28 ) compared with the control group . After 6 months , significant between-group differences were maintained for maximum reach distance and peak vertical force through the affected foot during st and ing up . CONCLUSIONS The sitting training protocol was both feasible and effective in improving sitting and st and ing up early after stroke and somewhat effective six months later", "Objective : To investigate the effect of independent practice of sitting balance as an addition to st and ard physiotherapy treatment for patients with stroke . Design : R and omized controlled trial , using blocked r and omization procedure with 2:1 ratio . Subjects : In patients with diagnosis of stroke , having achieved one minute of independent sitting balance but not yet achieved 10 independent steps , and with no known previous disabilities , pathology or neurological de”cit affecting mobility prior to stroke . Intervention : A four-week regime of independent practice aim ed at improving aspects of balance , as an addition to st and ard physiotherapy treatment based on the Bobath Approach . Main outcome measure : Proportion of patients achieving ‘ normal ’ symmetry of weight distribution during sitting , st and ing , rising to st and , sitting down , and reaching . Results : Nineteen subjects were r and omized to the control group ; nine to the intervention group . There were no clinical ly signi”cant differences in measured outcome between the groups . Conclusions : The regime of independent practice had no measured bene”cial effect on the balance ability of patients with recently acquired stroke", "Objective : To examine the effectiveness of task-oriented progressive resistance strength training on lower extremity strength and functional performance in chronic stroke subjects . Design : Single-blind , r and omized controlled trial . Setting : Medical centre and district hospital . Subjects : Forty-eight subjects at least one year post stroke . Interventions : Participants r and omly allocated to two groups , control ( n-/24 ) and experimental ( n-/24 ) . Subjects in the control group did not receive any rehabilitation training . Subjects in the experimental group were put on a four-week task-oriented progressive resistance strength training . Main measures : Lower extremity muscle strength , gait velocity , cadence , stride length , six-minute walk test , step test , and timed up and go test . Results : Muscle strength significantly improved in the experimental group for strong side muscle groups ( ranged from 23.9 % to 36.5 % ) and paretic side muscle groups ( ranged from 10.1 % to 77.9 % ) . In the control group muscle strength changes ranged from 6.7 % gain to 11.2 % decline . The experimental group showed significant improvement in all selected measures of functional performance except for the step test . In the control group , the number of repetitions of the step test significantly decreased ( -20.3 % ) with no change in other functional tests . There was a significant difference between groups for muscle strength and all functional measures . The strength gain was significantly associated with gain in the functional tests . Conclusions : The task-oriented progressive resistance strength training programme could improve lower extremity muscle strength in individuals with chronic stroke and could carry over into improvement in functional abilities" ]	41189d20-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Growing evidence suggests that second-generation cryoballoon ablation ( 2G-CB ) is effective in patients with persistent atrial fibrillation ( PerAF ) . The cornerstone of atrial fibrillation ( AF ) ablation is pulmonary vein isolation ( PVI ) . The purpose of this study was to summarize the available data on the safety and mid-term ( ≥ 12 months ) effectiveness of a ' PVI-only ' strategy vs. a ' PVI-plus ' strategy using 2G-CB in patients with PerAF . METHODS We search ed the PubMed , EMBASE and Cochrane library data bases for studies on 2G-CB for PerAF . Group analysis was based on the ablation approach : ' PVI-only ' versus ' PVI-plus ' , the latter of which involved PVI plus other substrate modifications . Studies showing clinical success rates at a follow-up ( FU ) of ≥ 12 months were included . Complication rates were also assessed . Data were analyzed by applying a fixed effects model . RESULTS A total of 879 patients from 5 studies were analyzed . After a mid-term FU of 27 months , the overall success rate of 2G-CB for PerAF was 66.1 % . In the ' PVI-plus ' group , the success rate was 73.8 % . In the ' PVI-only ' group , the success rate was 53.6 % . No heterogeneity was noted among studies ( I2 = 0.0 % , P = 0.82 ) . Complications occurred in 5.2 % of patients ( P = 0.93 ) , and the rate of phrenic nerve ( PN ) injury was 2.8 % ( P = 0.14 ) . Vascular assess complications were the most frequent at 1.6 % ( P = 0.33 ) . No death or myocardial infa rct ion was reported . CONCLUSION ' PVI-plus ' involving 2G-CB seems to be safe and effective for treating PerAF	[ "AIM Telemonitoring ( TM ) is a safe and efficient monitoring system for internal cardioverter defibrillator device ( ICD ) recipients . TM has been used to track info on the clinical status of heart failure patients treated by ICD and /or cardiac resynchronisation therapy defibrillator ( CRT-D ) . The aim of this study was to investigate the impact of TM on clinical outcomes in a population of CRT-D patients with heart failure . METHODS In a multicentre , r and omised study , patients with chronic heart failure , New York Heart Association ( NYHA ) functional class II or III , left bundle branch block , severe left ventricle ejection fraction reduction ( LVEF RESULTS One hundred and ninety-one patients have been r and omised to receive either a CRT-D with TM or a CRT-D with traditional ambulatory monitoring ( control group ) and completed the 12-month study follow-up . Primary endpoints were all cause death , cardiac death and hospital admission for heart failure . Secondary endpoints were atrial fibrillation , sustained episodes , non-sustained and self terminated ventricular tachyarrhythmia , sustained ventricular tachycardia , and ventricular fibrillation , ICD shocks and percentage of CRT-D responder patients . Univariate analysis identified the following factors predicting hospitalisation : TM , age , chronic kidney disease , hypercholesterolaemia , LVEF and NYHA class . At multivariate analysis , TM was the only factor predicting heart failure hospitalisation ( hazard ratio 0.6 , 0.42 - 0.79 , 95 % CI , p = 0.002 ) , without affecting overall mortality and cardiac deaths events . CONCLUSIONS Taken together , our data indicate the importance of TM in predicting heart failure hospitalisation in patients treated with", "Aims The ESC-EHRA Atrial Fibrillation Ablation Long-Term registry is a prospect i ve , multinational study that aims at providing an accurate picture of contemporary real-world ablation for atrial fibrillation ( AFib ) and its outcome . Methods and results A total of 104 centres in 27 European countries participated and were asked to enrol 20–50 consecutive patients scheduled for first and re-do AFib ablation . Pre-procedural , procedural and 1-year follow-up data were captured on a web-based electronic case record form . Overall , 3630 patients were included , of which 3593 underwent an AFib ablation ( 98.9 % ) . Median age was 59 years and 32.4 % patients had lone atrial fibrillation . Pulmonary vein isolation was attempted in 98.8 % of patients and achieved in 95–97 % . AFib-related symptoms were present in 97 % . In-hospital complications occurred in 7.8 % and one patient died due to an atrioesophageal fistula . One-year follow-up was performed in 3180 ( 88.6 % ) at a median of 12.4 months ( 11.9–13.4 ) after ablation : 52.8 % by clinical visit , 44.2 % by telephone contact and 3.0 % by contact with the general practitioner . At 12-months , the success rate with or without antiarrhythmic drugs ( AADs ) was 73.6 % . A significant portion ( 46 % ) was still on AADs . Late complications included 14 additional deaths ( 4 cardiac , 4 vascular , 6 other causes ) and 333 ( 10.7 % ) other complications . Conclusion AFib ablation in clinical practice is mostly performed in symptomatic , relatively young and otherwise healthy patients . Overall success rate is satisfactory , but complication rate remains considerable and a significant portion of patients remain on AADs . Monitoring after ablation shows wide variations . Antithrombotic treatment after ablation shows insufficient guideline -adherence", "Abstract Aims The primary safety and efficacy endpoints of the r and omized FIRE AND ICE trial have recently demonstrated non-inferiority of cryoballoon vs. radiofrequency current ( RFC ) catheter ablation in patients with drug-refractory symptomatic paroxysmal atrial fibrillation ( AF ) . The aim of the current study was to assess outcome parameters that are important for the daily clinical management of patients using key secondary analyses . Specifically , re interventions , rehospitalizations , and quality -of-life were examined in this r and omized trial of cryoballoon vs. RFC catheter ablation . Methods and results Patients ( 374 subjects in the cryoballoon group and 376 subjects in the RFC group ) were evaluated in the modified intention-to-treat cohort . After the index ablation , log-rank testing over 1000 days of follow-up demonstrated that there were statistically significant differences in favour of cryoballoon ablation with respect to repeat ablations ( 11.8 % cryoballoon vs. 17.6 % RFC ; P = 0.03 ) , direct-current cardioversions ( 3.2 % cryoballoon vs. 6.4 % RFC ; P = 0.04 ) , all-cause rehospitalizations ( 32.6 % cryoballoon vs. 41.5 % RFC ; P = 0.01 ) , and cardiovascular rehospitalizations ( 23.8 % cryoballoon vs. 35.9 % RFC ; P quality -of-life surveys ( both mental and physical ) as measured by the Short Form-12 health survey and the EuroQol five-dimension question naire . There was an improvement in both mental and physical quality -of-life in all patients that began at 6 months after the index ablation and was maintained throughout the 30 months of follow-up . Conclusion Patients treated with cryoballoon as opposed to RFC ablation had significantly fewer repeat ablations , direct-current cardioversions , all-cause rehospitalizations , and cardiovascular rehospitalizations during follow-up . Both patient groups improved in quality -of-life scores after AF ablation . Clinical trial registration Clinical Trials.gov identifier : NCT01490814", "OBJECTIVES This study sought to assess the safety and effectiveness of a novel cryoballoon ablation technology design ed to achieve single-delivery pulmonary vein ( PV ) isolation . BACKGROUND St and ard radiofrequency ablation is effective in eliminating atrial fibrillation ( AF ) but requires multiple lesion delivery at the risk of significant complications . METHODS Patients with documented symptomatic paroxysmal AF and previously failed therapy with ≥ 1 membrane active antiarrhythmic drug underwent 2:1 r and omization to either cryoballoon ablation ( n = 163 ) or drug therapy ( n = 82 ) . A 90-day blanking period allowed for optimization of antiarrhythmic drug therapy and reablation if necessary . Effectiveness of the cryoablation procedure versus drug therapy was determined at 12 months . RESULTS Patients had highly symptomatic AF ( 78 % paroxysmal , 22 % early persistent ) and experienced failure of at least one antiarrhythmic drug . Cryoablation produced acute isolation of three or more PVs in 98.2 % and all four PVs in 97.6 % of patients . PVs isolation was achieved with the balloon catheter alone in 83 % . At 12 months , treatment success was 69.9 % ( 114 of 163 ) of cryoblation patients compared with 7.3 % of antiarrhythmic drug patients ( absolute difference , 62.6 % [ p recurrent , symptomatic AF , constituting drug treatment failure . There were 7 of the result ing 228 cryoablated patients ( 3.1 % ) with a > 75 % reduction in PV area during 12 months of follow-up . Twenty-nine of 259 procedures ( 11.2 % ) were associated with phrenic nerve palsy as determined by radiographic screening ; 25 of these had resolved by 12 months . Cryoablation patients had significantly improved symptoms at 12 months . CONCLUSIONS The STOP AF trial demonstrated that cryoballoon ablation is a safe and effective alternative to antiarrhythmic medication for the treatment of patients with symptomatic paroxysmal AF , for whom at least one antiarrhythmic drug has failed , with risks within accepted st and ards for ablation therapy . ( A Clinical Study of the A rct ic Front Cryoablation Balloon for the Treatment of Paroxysmal Atrial Fibrillation [ Stop AF ] ; NCT00523978 )", "INTRODUCTION There are limited comparative data on catheter ablation of atrial fibrillation ( CAAF ) using the second-generation cryoballoon ( CB-2 ) versus point-by-point radiofrequency ( RF ) . This study examines the acute/long-term CAAF outcomes using these 2 strategies . METHODS AND RESULTS In this multicenter , retrospective , nonr and omized analysis , procedural and clinical outcomes of 1,196 patients ( 76 % with paroxysmal AF ) undergoing CAAF using CB-2 ( n = 773 ) and open-irrigated , non-force sensing RF ( n = 423 ) were evaluated . Pulmonary vein isolation was achieved in 98 % with CB-2 and 99 % with RF ( P = 0.168 ) . CB-2 was associated with shorter ablation time ( 40 ± 14 min vs. 66 ± 26 min ; P and procedure time ( 145 ± 49 minutes vs. 188 ± 42 minutes ; P greater fluoroscopic utilization ( 29 ± 13 minutes vs. 23 ± 14 minutes ; P transient ( 7.6 % vs. 0 % ; P persistent ( 1.2 % vs. 0 % ; P = 0.026 ) phrenic nerve palsy occurred exclusively with CB-2 , other adverse event rates were similar between CB-2 ( 1.6 % ) and RF ( 2.6 % ) ; P = 0.207 . However , freedom from AF/atrial flutter/tachycardia at 12 months following a single procedure without antiarrhythmic therapy was greater with CB-2 ( 76.6 % ) versus RF ( 60.4 % ) ; P patients with paroxysmal AF ( P Additionally , CB-2 was associated with reduced long-term need for antiarrhythmic therapy ( 16.7 % vs. 22.0 % ; P = 0.024 ) and repeat ablations ( 14.6 % vs. 24.1 % ; P CB-2 coupled with RF as occasionally required was associated with greater freedom from atrial arrhythmias at 12 months following a single procedure without antiarrhythmic therapy when compared to open-irrigated , non-force sensing RF , alone", "OBJECTIVES The purpose of this study was to investigate long-term outcomes of freedom from atrial fibrillation ( AF ) after pulmonary vein ( PV ) isolation using cryoballoon ablation with balloon-size selection based on individual PV diameters . BACKGROUND Data are lacking on long-term outcomes from cryoablation and on the most effective balloon size . METHODS This was a prospect i ve observational study involving 605 consecutively enrolled patients with symptomatic paroxysmal AF ( n = 579 ) or persistent AF . Cryoballoon size was based on magnetic resonance imaging and /or conventional angiograms . Patients were followed up every 3 months during the first year after discharge and every 6 months in the second year . After 24 months , follow-up was on an outpatient basis with documented AF episodes recorded . RESULTS The PV isolation was achieved without touch-up in 91.1 % of patients , using the smaller balloon in 26.7 % , the larger balloon in 25.6 % , and both balloons in 47.7 % of patients . Follow-up data for > 12 months ( median 30 months ; interquartile range 18 to 48 months ) were available for 451 patients , 278 ( 61.6 % ) of whom were free of AF recurrence with no need for repeat procedures after the 3-month blanking period . Rates of freedom from AF after 1 , 2 , and 3 repeat procedures ( using cryoballoon or radiofrequency ablation with similar success rates ) were 74.9 % , 76.2 % , and 76.9 % , respectively . Use of the smaller balloons or both balloons produced the highest rates of long-term freedom from AF . Phrenic nerve palsy occurred in 12 patients ( 2 % ) , resolving within 3 to 9 months . CONCLUSIONS Rates of long-term freedom from AF after cryoballoon ablation are similar to those reported for radiofrequency ablation . A choice between balloons may improve outcomes", "Background — There is a lack of data on the comparative efficacy and procedural safety of open irrigated radiofrequency ( RF ) and cryoballoon catheter ( CB ) ablation for pulmonary vein isolation in patients with paroxysmal atrial fibrillation . Methods and Results — In a prospect i ve , noninferiority study , 315 patients were r and omly assigned to RF ( n=159 ) or CB ( n=156 ) ablation . The primary end point was freedom from atrial arrhythmia with absence of persistent complications . Patients were largely comparable between groups with more vascular disease in the RF group ( 8.2 % versus 2.6 % for CB ; P=0.028 ) . The primary end point at 12 months was achieved by 70.7 % with RF and 73.6 % with CB ( multiple procedure success ) , including 31 redo procedures in each group ( 19.5 % of RF versus 19.9 % of CB ; P=0.933 ) . For the intention-to-treat population , noninferiority of CB was revealed for the predefined inferiority margin ( risk difference , 0.029 ; 95 % confidence interval , −0.074 to 0.132 ; P Rates at 6 months were 63.1 % and 64.1 % for the RF and CB groups ( single procedure success ) , and noninferiority was confirmed ( risk difference , 0.010 ; 95 % confidence interval , −0.097 to 0.116 ; P=0.002 ) . Periprocedural complications for the index procedure were more frequent in the CB group ( 5.0 % RF , 12.2 % CB ; P=0.022 ) with a significant difference in phrenic nerve palsies ( 0 % RF , 5.8 % CB ; P=0.002 ) . Conclusion — This large , prospect i ve , r and omized , controlled study demonstrates noninferiority of CB ablation versus RF ablation for treating patients with paroxysmal atrial fibrillation . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00774566", "INTRODUCTION Data on long-term outcomes of cryoballoon ( CB ) ablation for treatment of persistent atrial fibrillation ( AF ) are sparse . Here , we report the first 3-year follow-up results and predictors of success for catheter ablation using the second-generation CB in patients with persistent AF . METHODS AND RESULTS For this prospect i ve observational study , we enrolled 101 patients ablated with the second-generation CB at our institution . The endpoint was the first documented recurrence ( > 30 seconds ) of AF , atrial flutter , or atrial tachycardia after a 3-month blanking period . Follow-up data were collected during outpatient clinic visits and included Holter-ECG recordings . The impact of several variables on recurrence was evaluated by means of univariate and multivariate analyses and Cox proportional hazards regression models . After a median follow-up of 37 ( 31 of 42 ) months , recurrence was documented in 30 patients ( 29.7 % ) . The median procedure and fluoroscopy times were 120 ( 102 of 147 ) and 20 ( 16 of 27 ) minutes , respectively . Phrenic nerve palsy occurred in 2.0 % of the patients . Among the 30 patients who experienced recurrence , 16 underwent repeat ablation in radiofrequency technique . Cox regression analysis showed that left atrial area > 21 cm2 and AF history duration > 2 years independently predicted recurrence . CONCLUSIONS Sinus rhythm was maintained in a substantial proportion of patients even 3 years after CB ablation . Patients with a nonenlarged left atrium and short AF history had the best outcome", "AIMS To assess the 1 year efficacy of pulmonary vein isolation ( PVI ) as index procedure for persistent atrial fibrillation ( PersAF ) comparing conventional radiofrequency irrigated-tip catheter ablation ( RFCA ) using contact-force technology and ablation using the second-generation cryoballoon ( CB-AdvA ) . METHODS AND RESULTS One hundred consecutive patients ( 74 male , 74 % ; mean age 62.4 ± 9.6 years ) with drug-refractory PersAF undergoing PVI using RFCA and CB-AdvA were enrolled . Follow-up was based on outpatient clinic visits including Holter-electrocardiograms . Recurrence of atrial tachyarrhythmias ( ATas ) was defined as a symptomatic or documented episode > 30 s. Among 100 patients , 50 underwent RFCA whereas 50 CB-AdvA. Mean procedure and fluoroscopy times were 90.5 ± 41.7 vs. 140.2 ± 46.9 min and 14.5 ± 6.6 vs. 19.8 ± 6.8 min in the CB-Adv and in the RFCA group , respectively ( P BP ) , freedom from ATas off-drugs after a single procedure was 60 % ( 28/50 patients ) in the CB-Adv and 56 % ( 27/50 patients ) in the RFCA group ( P = 0.71 ) . Multivariate analysis demonstrated that PersAF duration ( P = 0.01 ) and relapses during BP ( P = 0.02 ) were independent predictors of ATa recurrences following the index procedure . CONCLUSION Freedom from ATas following PersAF ablation with RFCA and CB-Adv is comparable at 1 year follow-up after a single procedure . Ablation with the CB-Adv is associated with shorter procedure time and radiation exposure as compared with RFCA . Atrial tachyarrhythmias occurrence during BP and longer time of PersAF seem to be significant predictors of arrhythmia recurrences after the index procedure", "BACKGROUND Catheter ablation is used extensively with curative intention in atrial fibrillation . Radiofrequency ablation has long been a st and ard of care , while cryoballoon technology has emerged as a feasible approach with promising results . Prospect i ve multicenter registry data referring to both ablation technologies in AF ablation therapy are lacking . METHODS Between January 2007 and August 2011 , a total of 3,775 consecutive patients with symptomatic paroxysmal AF who underwent PV ablation in their respective centers were enrolled . The cohort was divided into 2 groups according to the ablation energy source used : cryoballoon ablation ( group 1 , n = 905 [ 24.0 % ] , median age 63 years , 64.3 % men ) and RF ablation ( group 2 , n = 2870 [ 76.0 % ] , median age 63 years , 62.7 % men ) . Comorbidities and baseline clinical characteristics were similar in both groups . RESULTS Acute success rate was similar in both groups ( 97.5 % in cryo vs 97.6 % in RF ; P = 0.81 ) . Procedure times were similar , ablation and fluoroscopy times were higher in cryoballoon when compared to RF ablation . Overall complication rate was similar in cryo- ( 4.6 % ) and RF-ablation ( 4.6 % ; P = 1.0 ) . Phrenic nerve palsy was more often in cryo versus RF ablation ( 2.1 % in cryo vs 0.0 % in RF ; P Other complications were more common in RF compared to cryoablation ( 4.6 % in RF vs 2.7 % in cryo ; P RF ablation is the most widespread ablation method in Germany , but use of cryoballoon increased significantly . Procedure times were similar , but ablation and fluoroscopy times were longer in cryoballoon ablation . No significant differences were found in terms of acute success and overall complication rate", "AIMS Cryoballoon ( CB ) ablation with the second-generation cryoballoon ( CBG2 ) seems to be more effective than its predecessor [ first-generation cryoballoon ( CBG1 ) ] , but phrenic nerve palsies were observed more frequently . The aim of this study was to compare the safety and efficacy of CBG1 and CBG2 in a sub study of the prospect i ve multicentre , multinational FREEZE Cohort Study . METHODS AND RESULTS Periprocedural data were analysed , and a total of 532 patients with paroxysmal atrial fibrillation ( AF ) were examined ( n = 224 for CBG1 and n = 308 for CBG2 ) . Procedure time decreased significantly from 149 to 130 min when comparing CBG1 with CBG2 ( P pulmonary vein isolation ( PVI ) was achieved in 97.8 and 97.6 % of PVs with CBG1 and CBG2 ( P = 0.77 ) , respectively . The need for dual-balloon usage within a procedure dropped ( 20.1 vs. 9.0 % , P fluoroscopy time was reduced when operating the CBG2 . Atrial fibrillation recurrence rates until discharge were similar ( 5.0 vs. 5.8 % , P = 0.69 ) . Comparable low rates of major complications were observed with both CBs , and there was a non-significant trend for more phrenic nerve palsies . CONCLUSION Second-generation cryoballoon demonstrated a high rate of acute PVI in a significant faster procedure , which also utilized less radiation exposure and less dual-balloon usage during an average procedure . The safety profile remains favourable with a non-significant trend for more phrenic nerve palsies . If the enhancements lead to a higher clinical benefit has to be determined . The 1-year outcome data from the ongoing FREEZE Cohort Study comparing radiofrequency and CB ablation will shed some light on that issue . CLINICAL TRIALS GOV IDENTIFIER NCT01360008", "BACKGROUND Phrenic nerve palsy ( PNP ) is the most frequently observed complication during cryoballoon ablation ( CB ; A rct ic Front , Medtronic , MN ) occurring in roughly 7%-9 % of the cases . The new second-generation cryoballoon ablation A rct ic Front Advance ( CB-A ) ( A rct ic Front ) has recently been launched in the market . OBJECTIVE To evaluate the incidence of right PNP with the new CB-A in comparison with the first-generation balloon in a series of consecutive patients that underwent pulmonary vein isolation with this modality . METHODS The study was design ed as an observational study with a prospect i ve follow-up . In total , 121 consecutive patients were included : 80 patients with the CB ( group 1 ) and 41 with the CB-A ( group 2 ) . RESULTS Mean procedural times , fluoroscopic times , and time to pulmonary vein isolation documented by real-time recordings were significantly lower in group 2 ( P ≤ .05 ) . The occurrence of PNP was significantly higher in group 2 ( 6.25 % [ 5 of 80 ] in group 1 vs 19.5 % [ 8 of 41 ] in group 2 ; P = .033 ) . At 7 months , PNP persisted in 1 ( 2.5 % ) patient in the CB-A group . CONCLUSIONS Right PNP seems to occur in a significantly larger number of patients with the second-generation CB-A. However , this complication is reversible in nearly all cases on short-term follow-up . More refined phrenic nerve monitoring during right-sided pulmonary vein ablation and less vigorous wedging maneuvers in the pulmonary vein ostia might significantly reduce the occurrence of this complication", "Catheter ablation ( CA ) is a procedure commonly used to restore sinus rhythm in patients with atrial fibrillation ( AF ) . However , AF recurrence after CA remains a relevant clinical issue . We tested the effects of an oral antioxidant treatment ( alpha lipoic acid [ ALA ] ) on AF recurrence post-CA . Patients with paroxysmal AF have been enrolled in a r and omized , prospect i ve , double-blind , controlled placebo trial . After CA , patients have been r and omly assigned to receive ALA oral supplementation ( ALA group ) or placebo ( control group ) and evaluated at baseline and after a 12-month follow-up : 73 patients completed the 12-month follow-up ( ALA : 33 and control : 40 ) . No significant difference has been detected between the 2 groups at baseline . Strikingly , 1 year after CA , ALA therapy significantly reduced serum markers of inflammation . However , there was no significant difference in AF recurrence events at follow-up comparing ALA with placebo group . Multivariate analysis revealed that the only independent prognostic risk factor for AF recurrence after CA is age . In conclusion , ALA therapy reduces serum levels of common markers of inflammation in ablated patients . Nevertheless , ALA does not prevent AF recurrence after an ablative treatment" ]	41189d5c-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Vitamin D may play a role in skeletal muscle because of the discovery of VDR in skeletal muscle . However , vitamin D deficiency is a global problem , including athletes . Studies examining the effect of vitamin D supplementation on muscle function in athletes have inconsistent results . Therefore , we aim ed to quantitatively summarize the evidence for the effect of vitamin D supplementation on skeletal muscle strength and explosive power of athletes using a meta- analysis . METHODS PubMed , EMBASE , Cochrane Library , and Web of Science were search ed for studies to identify r and omized controlled trials or controlled trials meeting the inclusion criteria . By a meta- analysis , effect sizes ( st and ardized mean differences , SMD ) with 95 % confidence intervals ( CI ) was calculated to compare reported outcomes across studies , I2 index was used to assessing heterogeneity , and heterogeneity factors were identified by regression analysis . The potential publication and sensitivity analyses were also assessed . RESULTS Eight RCTs involving 284 athletes were included . The protocol s used to evaluate the muscle strength of athletes were inconsistent across the included studies , and muscle explosive power was assessed via vertical jump tests . The results indicated that vitamin D supplementation had no impact on overall muscle strength outcomes ( SMD 0.05 , 95 % CI : -0.39 to 0.48 , p = 0.84 ) . In subgroup analysis , vitamin D supplementation had an effect on lower-limb muscle strength ( SMD 0.55 , 95 % CI:0.12 to 0.98 , p = 0.01 ) but not upper-limb muscle strength ( SMD -0.19 , 95 % CI:-0.73 to 0.36 , p = 0.50 ) or muscle explosive power ( SMD 0.05 , 95 % CI:-0.24 to 0.34 , p = 0.73 ) . Vitamin D supplementation was more effective for athletes trained indoors ( SMD 0.48 , 95 % CI:0.06 to 0.90 , p = 0.02 ) . CONCLUSIONS Vitamin D supplementation positively affected lower limb muscle strength in athletes , but not upper limb muscle strength or muscle power . Different muscle groups and functions may respond differently to vitamin D supplementation . Additional studies should focus on determining the appropriate vitamin D supplementation methods and optimal serum 25(OH)D levels for athletes . REGISTRATION The protocol for our study is registered in the international prospect i ve register of systematic review s ( PROSPERO registration number CRD42016045872 )	[ "It is hypothesized that vitamin D insufficiency in athletes might negatively affect sport performance . The objective of this study was to examine the effect of vitamin D3 supplementation on physical performance of adolescent swimmers with vitamin D insufficiency . Fifty-three adolescent competitive swimmers with vitamin D insufficiency ( serum 25-hydroxyvitamin-D concentrations ( 25(OH)D ) were r and omized to receive 2,000 IU/day of vitamin D3 or placebo for 12 weeks . Swimming performance at several speeds , arm-grip strength , and one-legged balance , were measured before and after supplementation . The age-adjusted changes in performance variables during the study were compared between groups . 25(OH ) D concentrations at study end were significantly higher in the vitamin group compared with the placebo group ( 29.6 ± 6.5 ng/ml vs. 20.3 ± 4.2 ng/ml , p the performance variables tested . No significant differences in performance were found between participants that became vitamin D sufficient , and those who did not . No significant correlation was found between the change in serum 25(OH)D and age-adjusted balance , strength or swimming performance at study end . Vitamin D3 supplementation that raised serum 25(OH)D concentrations by a mean of 9.3 ng/ml above placebo in adolescent swimmers with vitamin D insufficiency , did not improve physical performance more than placebo", "IMPORTANCE Vitamin D deficiency has been associated with poor physical performance . OBJECTIVE To determine the effectiveness of high-dose vitamin D in lowering the risk of functional decline . DESIGN , SETTING , AND PARTICIPANTS One-year , double-blind , r and omized clinical trial conducted in Zurich , Switzerl and . The screening phase was December 1 , 2009 , to May 31 , 2010 , and the last study visit was in May 2011 . The date s of our analysis were June 15 , 2012 , to October 10 , 2015 . Participants were 200 community-dwelling men and women 70 years and older with a prior fall . INTERVENTIONS Three study groups with monthly treatments , including a low-dose control group receiving 24,000 IU of vitamin D3 ( 24,000 IU group ) , a group receiving 60,000 IU of vitamin D3 ( 60,000 IU group ) , and a group receiving 24,000 IU of vitamin D3 plus 300 μg of calcifediol ( 24,000 IU plus calcifediol group ) . MAIN OUTCOMES AND MEASURES The primary end point was improving lower extremity function ( on the Short Physical Performance Battery ) and achieving 25-hydroxyvitamin D levels of at least 30 ng/mL at 6 and 12 months . A secondary end point was monthly reported falls . Analyses were adjusted for age , sex , and body mass index . RESULTS The study cohort comprised 200 participants ( men and women ≥ 70 years with a prior fall ) . Their mean age was 78 years , 67.0 % ( 134 of 200 ) were female , and 58.0 % ( 116 of 200 ) were vitamin D deficient ( . Intent-to-treat analyses showed that , while 60,000 IU and 24,000 IU plus calcifediol were more likely than 24,000 IU to result in 25-hydroxyvitamin D levels of at least 30 ng/mL ( P = .001 ) , they were not more effective in improving lower extremity function , which did not differ among the treatment groups ( P = .26 ) . However , over the 12-month follow-up , the incidence of falls differed significantly among the treatment groups , with higher incidences in the 60,000 IU group ( 66.9 % ; 95 % CI , 54.4 % to 77.5 % ) and the 24,000 IU plus calcifediol group ( 66.1 % ; 95 % CI , 53.5%-76.8 % ) group compared with the 24,000 IU group ( 47.9 % ; 95 % CI , 35.8%-60.3 % ) ( P = .048 ) . Consistent with the incidence of falls , the mean number of falls differed marginally by treatment group . The 60,000 IU group ( mean , 1.47 ) and the 24,000 IU plus calcifediol group ( mean , 1.24 ) had higher mean numbers of falls compared with the 24,000 IU group ( mean , 0.94 ) ( P = .09 ) . CONCLUSIONS AND RELEVANCE Although higher monthly doses of vitamin D were effective in reaching a threshold of at least 30 ng/mL of 25-hydroxyvitamin D , they had no benefit on lower extremity function and were associated with increased risk of falls compared with 24,000 IU . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01017354", "Vitamin D insufficiency is common in athletes and may lower physical performance . Many cross-sectional studies associate vitamin D status with physical performance in athletes ; however , there have been few prospect i ve r and omized controlled trials with adequate statistical power to test this relationship , and none in the southern hemisphere . Thus , a prospect i ve double-blind , r and omized , placebo-controlled intervention trial was conducted involving 57 professional rugby union players in New Zeal and . Participants were r and omized to receive 50,000 IU of cholecalciferol ( equivalent to 3,570 IU/day ) or placebo once every two weeks over 11 - 12 weeks . Serum 25(OH)D concentrations and physical performance were measured at baseline , weeks 5 - 6 , and weeks 11 - 12 . Mean ( SD ) serum 25(OH)D concentrations for all participants at baseline was 94 ( 18 ) nmol/L , with all players above 50 nmol/L. Vitamin D supplementation significantly increased serum 25(OH)D concentrations compared to placebo , with a 32 nmol/L difference between groups at 11 - 12 weeks ( 95 % CI , 26 - 38 ; p Performance in five of the six tests at study completion , including the primary outcome variable of 30-m sprint time , did not differ between the vitamin D supplemented and placebo groups ( p > 0.05 ) . Performance on the weighted reverse-grip chin up was significantly higher in players receiving vitamin D compared with placebo , by 5.5 kg ( 95 % CI , 2.0 - 8.9 ; p = 0.002 ) . Despite significantly improving vitamin D status in these professional rugby union players , vitamin D supplementation had little impact on physical performance outcomes . Thus , it is unlikely that vitamin D supplementation is an ergogenic aid in this group of athletes", "CONTEXT Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures ; however , adherence to daily supplementation is typically poor . OBJECTIVE To determine whether a single annual dose of 500,000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture . DESIGN , SETTING , AND PARTICIPANTS A double-blind , placebo-controlled trial of 2256 community-dwelling women , aged 70 years or older , considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were r and omly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years . The study concluded in 2008 . INTERVENTION 500,000 IU of cholecalciferol or placebo . MAIN OUTCOME MEASURES Falls and fractures were ascertained using monthly calendars ; details were confirmed by telephone interview . Fractures were radiologically confirmed . In a sub study , 137 r and omly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels . RESULTS Women in the cholecalciferol ( vitamin D ) group had 171 fractures vs 135 in the placebo group ; 837 women in the vitamin D group fell 2892 times ( rate , 83.4 per 100 person-years ) while 769 women in the placebo group fell 2512 times ( rate , 72.7 per 100 person-years ; incidence rate ratio [ RR ] , 1.15 ; 95 % confidence interval [ CI ] , 1.02 - 1.30 ; P = .03 ) . The incidence RR for fracture in the vitamin D group was 1.26 ( 95 % CI , 1.00 - 1.59 ; P = .047 ) vs the placebo group ( rates per 100 person-years , 4.9 vitamin D vs 3.9 placebo ) . A temporal pattern was observed in a post hoc analysis of falls . The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months ( test for homogeneity ; P = .02 ) . In the sub study , the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3 % of the sub study participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group , 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L , were approximately 90 nmol/L at 3 months , and remained higher than the placebo group 12 months after dosing . CONCLUSION Among older community-dwelling women , annual oral administration of high-dose cholecalciferol result ed in an increased risk of falls and fractures . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12605000658617 ; is rct n.org Identifier : IS RCT N83409867", "OBJECTIVES To evaluate a dynamic form of weighted vest exercise suitable for home use and design ed to enhance muscle power , balance , and mobility . DESIGN A single-blind , r and omized , controlled trial . SETTING Outpatient exercise research facility situated within an academic long-term care center . PARTICIPANTS Twenty-one community-dwelling women aged 70 and older with a Short Physical Performance Battery ( SPPB ) score between 4 and 10 ( out of 12 ) . INTERVENTIONS Subjects were r and omized into a progressive resistance-training program using weighted vests for resistance with exercises design ed to be specific to mobility tasks and have a component performed at the fastest possible velocity ( Increased Velocity Exercise Specific to Task ( InVEST ) , n=11 ) or a control exercise group ( control , n=10 ) , which performed slow-velocity , low-resistance exercise . Both groups exercised three times a week for 12 weeks . MEASUREMENTS Changes in muscle power , balance , and physical performance were compared . RESULTS In comparison to control group , InVEST group manifested significant improvements ( P leg power across measurements obtained at 75 % to 90 % of the one-repetition maximum . Both groups demonstrated significant improvements in chair st and and SPPB score from baseline , and the InVEST group showed significant improvements in gait speed and chair st and from baseline ( P chair st and time than control ( P leg power and chair rise in this population and is worthy of further investigation as a means of enhancing balance and mobility", "Data were pooled from four r and omized clinical trials with vitamin D performed in Tromsø with weight reduction , insulin sensitivity , bone density , and depression scores as endpoints . Serum lipids , glycated hemoglobin ( HbA1c ) , and high sensitivity C-Reactive Protein , ( HS-CRP ) were measured at baseline and after 6–12 months of supplementation with vitamin D 20 000 IU–40 000 IU per week versus placebo . A total of 928 subjects who completed the interventions were included . At baseline the mean serum 25-hydroxyvitamin D ( 25(OH)D ) level in those given vitamin D was 55.9 ( 20.9 ) nmol/L and the mean increase was 82.4 ( 40.1 ) nmol/L. Compared with the placebo group there was in the vitamin D group at the end of the studies a slight , but significant , increase in HbA1c of 0.04 % , an increase in HS-CRP of 0.07 mg/L in those with serum 25(OH)D baseline HDL-C and serum 25(OH)D decrease serum HDL-C of 0.08 mmol/L ( P No serious side-effects were seen . In conclusion , in subjects without vitamin D deficiency , there is no improvement in serum lipids , HbA1c , or HS-CRP with high dose vitamin D supplementation . If anything , the effect is negative", "OBJECTIVE Vitamin D supplementation is suggested to reduce the risk of falls among ambulatory or institutionalized elderly subjects . The present study was undertaken to address the reduced risk of falls and hip fractures in patients with long-st and ing stroke by vitamin D supplementation . METHODS Ninety-six elderly women with poststroke hemiplegia were followed for two years . Patients were r and omly assigned to one of the two groups , and 48 patients received 1,000 IU ergocalciferol daily , and the remaining 48 received placebo . The number of falls per person and incidence of hip fractures were compared between the two groups . Strength and tissue ATPase of skeletal muscles on the nonparetic side were assessed before and after the study . RESULTS At baseline , serum 25-hydroxyvitamin D levels were in the deficient range ( vitamin D treatment enhanced serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels . Vitamin D treatment accounted for a 59 % reduction in falls ( 95 % CI , 28 - 81 % ; p = 0.003 ) . There were increases in the relative number and size of type II muscle fibers and improved muscle strength in the vitamin D-treated group . Hip fractures occurred in 4 of 48 placebo group and 0 in 48 vitamin D2 group during the 2-year study period ( log-rank , p = 0.049 ) . CONCLUSION Vitamin D may increase muscle strength by improving atrophy of type II muscle fibers , which may lead to decreased falls and hip fractures", "Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists", "The age-related change in hormone concentrations has been hypothesized to play a role in the loss of muscle mass and muscle strength with aging , also called sarcopenia . The aim of this prospect i ve study was to investigate whether low serum 25-hydroxyvitamin D ( 25-OHD ) and high serum PTH concentration were associated with sarcopenia . In men and women aged 65 yr and older , participants of the Longitudinal Aging Study Amsterdam , grip strength ( n = 1008 ) and appendicular skeletal muscle mass ( n = 331 , using dual-energy x-ray absorptiometry ) were measured in 1995 - 1996 and after a 3-yr follow-up . Sarcopenia was defined as the lowest sex-specific 15th percentile of the cohort , translating into a loss of grip strength greater than 40 % or a loss of muscle mass greater than 3 % . After adjustment for physical activity level , season of data collection , serum creatinine concentration , chronic disease , smoking , and body mass index , persons with low ( 25-OHD levels were 2.57 ( 95 % confidence interval 1.40 - 4.70 , based on grip strength ) and 2.14 ( 0.73 - 6.33 , based on muscle mass ) times more likely to experience sarcopenia , compared with those with high ( > 50 nmol/liter ) levels . High PTH levels ( > or=4.0 pmol/liter ) were associated with an increased risk of sarcopenia , compared with low PTH ( grip strength , odds ratio = 2.35 ( 1.05 - 5.28 ) based on muscle mass . The associations were similar in men and women . The results of this prospect i ve , population -based study show that lower 25-OHD and higher PTH levels increase the risk of sarcopenia in older men and women", "OBJECTIVE Suboptimal mitochondrial function has been implicated in several disorders in which fatigue is a prominent feature . Vitamin D deficiency is a well-recognized cause of fatigue and myopathy . The aim of this study was to examine the effects of cholecalciferol therapy on skeletal mitochondrial oxidative function in symptomatic , vitamin D-deficient individuals . DESIGN This longitudinal study assessed mitochondrial oxidative phosphorylation in the gastrosoleus compartment using phosphorus-31 magnetic resonance spectroscopy measurements of phosphocreatine recovery kinetics in 12 symptomatic , severely vitamin D-deficient subjects before and after treatment with cholecalciferol . All subjects had serum assays before and after cholecalciferol therapy to document serum 25-hydroxyvitamin D ( 25OHD ) and bone profiles . Fifteen healthy controls also underwent (31)P-magnetic resonance spectroscopy and serum 25OHD assessment . RESULTS The phosphocreatine recovery half-time ( τ1/2PCr ) was significantly reduced after cholecalciferol therapy in the subjects indicating an improvement in maximal oxidative phosphorylation ( 34.44 ± 8.18 sec to 27.84 ± 9.54 sec , P improvement in mean serum 25OHD levels ( 8.8 ± 4.2 nmol/L to 113.8 ± 51.5 nmol/L , P difference in phosphate metabolites at rest . A linear regression model showed that decreasing serum 25OHD levels was associated with increasing τ1/2PCr ( r = -0.41 , P = .009 ) . All patients reported an improvement in fatigue after cholecalciferol therapy . CONCLUSIONS Cholecalciferol therapy augments muscle mitochondrial maximal oxidative phosphorylation after exercise in symptomatic , vitamin D-deficient individuals . This finding suggests that changes in mitochondrial oxidative phosphorylation in skeletal muscle could at least be partly responsible for the fatigue experienced by these patients . For the first time , we demonstrate a link between vitamin D and the mitochondria in human skeletal muscle", "BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from \" fair \" to \" substantial , \" and the reliability of the total PEDro score was \" fair \" to \" good .", "Background Vitamin D deficiency is common in the general public and athletic population s and may impair skeletal muscle function . We therefore assessed the effects of vitamin D3 supplementation on serum 25[OH]D concentrations and physical performance . Methods 30 club-level athletes were block r and omised ( using baseline 25[OH]D concentrations ) into one of three groups receiving either a placebo ( PLB ) , 20 000 or 40 000 IU/week oral vitamin D3 for 12 weeks . Serum 25[OH]D and muscle function ( 1-RM bench press and leg press and vertical jump height ) were measured presupplementation , 6 and 12 weeks postsupplementation . Vitamin D deficiency was defined in accordance with the US Institute of Medicine guideline ( 57 % of the subject population were vitamin D deficient at baseline ( mean±SD value 51±24 nmol/l ) . Following 6 and 12 weeks supplementation with 20 000 IU ( 79±14 and 85±10 nmol/l , respectively ) or 40 000 IU vitamin D3 ( 98±14 and 91±24 nmol/l , respectively ) , serum vitamin D concentrations increased in all participants , with every individual achieving concentrations greater than 50 nmol/l . In contrast , vitamin D concentration in the PLB group decreased at 6 and 12 weeks ( 37±18 and 41±22 nmol/l , respectively ) . Increasing serum 25[OH]D had no significant effect on any physical performance parameter ( p>0.05 ) . Conclusions Both 20 000 and 40 000 IU vitamin D3 supplementation over a 6-week period elevates serum 25[OH]D concentrations above 50 nmol/l , but neither dose given for 12 weeks improved our chosen measures of physical performance ", "Objective : Indoor athletes have been shown to be prone to vitamin D3 deficiency . The aim of the study was to examine the acute effects of vitamin D supplementation on muscle function using isokinetic dynamometry . Design : R and omized placebo-controlled , double-blind study . Setting : Institutional . Participants : Adult male white national level judoka athletes ( n = 22 ) who were involved in full-time training . Exclusion criteria were vitamin supplementation , overseas travel to sunny climes , and /or an injury incurred during the last 3 months before testing . Interventions : Subjects were r and omly allocated to the treatment ( 150 000IU vitamin D3 ) or placebo and given blinded supplements by an independent research er . Participants were tested twice , 8 days apart , on a Monday morning before the start of judo training and after 2 days of rest . A 5 to 7 mL of blood sample was collected followed by isokinetic concentric quadriceps and hamstring muscle function assessment s on the right leg at 30 and 200 ° ·s−1 . Main Outcome Measures : Repeated- measures analysis of variance was used to analyze isokinetic muscle force and serum 25(OH)D3 . Regression to the mean was used to examine changes in 25(OH)D3 levels over the study period . Results : The treatment group demonstrated a significant increase in serum 25(OH)D levels ( 34 % , P ⩽ 0.001 ) and muscle strength ( 13 % , P = 0.01 ) between days 1 and 8 . No significant differences were found for the placebo group for the same period . Conclusions : A single bolus of 150 000IU vitamin D3 had a significant positive effect on serum 25(OH)D levels and muscle function in vitamin D insufficient elite indoor athletes . Clinical Relevance : Serum 25(OH)D3 levels of indoor athletes should be monitored throughout the year and especially during winter months . Beneficial responses , in muscle strength and serum 25(OH)D3 , to 1 dose of vitamin D3 supplementation can be observed within 1 week of ingestion . Muscle strength is linked to serum 25(OH)D levels", "Abstract Incidence of vitamin D deficiency is increasing worldwide . The purpose of this study was to determine if supplementation with vitamin D2 from Portobello mushroom powder would enhance skeletal muscle function and attenuate exercise-induced muscle damage in low vitamin D status high school athletes . Participants were r and omised to Portobello mushroom powder ( 600 IU/d vitamin D2 ) or placebo for 6 weeks . Participants then completed a 1.5-h exercise session design ed to induce skeletal muscle damage . Blood sample s and measures of skeletal muscle function were taken pre-supplementation , post-supplementation/pre-exercise and post-exercise . Six weeks supplementation with vitamin D2 increased serum 25(OH)D2 by 9.9-fold and decreased serum 25(OH)D3 by 28 % . Changes in skeletal muscle function and circulating markers of skeletal muscle damage did not differ between groups . In conclusion , 600 IU/d vitamin D2 increased 25(OH)D2 with a concomitant decrease in 25(OD)D3 , with no effect on muscular function or exercise-induced muscle damage in high school athletes", "CONTEXT Studies examining whether vitamin D supplementation increases muscle mass or muscle-specific vitamin D receptor ( VDR ) concentration are lacking . OBJECTIVE Our objective was to determine whether vitamin D₃ 4000 IU/d alters muscle fiber cross-sectional area ( FCSA ) and intramyonuclear VDR concentration over 4 months . DESIGN AND SETTING This was a r and omized , double-blind , placebo-controlled study in a single center . PARTICIPANTS Participants were 21 mobility-limited women ( aged ≥ 65 years ) with serum 25-hydroxyvitamin D ( 25OHD ) levels of 22.5 to 60 nmol/L. MAIN OUTCOME MEASURES Baseline and 4-month FCSA and intramyonuclear VDR were measured from vastus lateralis muscle cross-sections probed for muscle fiber type ( I/IIa/IIx ) and VDR using immunofluorescence . RESULTS At baseline , mean ( ±SD ) age was 78 ± 5 years ; body mass index was 27 ± 5 kg/m² , 25OHD was 46.3 ± 9.5 nmol/L , and a short physical performance battery score was 7.95 ± 1.57 out of 12 . At 4 months , 25OHD level was 52.5 ± 17.1 ( placebo ) vs 80.0 ± 11.5 nmol/L ( vitamin D [ VD ] ; P , and change in 25OHD level was strongly associated with percent change in intramyonuclear VDR concentration-independent of group ( r = 0.87 , P change in intramyonuclear VDR concentration was 7.8 % ± 18.2 % ( placebo ) vs 29.7 % ± 11.7 % ( VD ; P = .03 ) with a more pronounced group difference in type II vs I fibers . Percent change in total ( type I/II ) FCSA was -7.4 % ± 18.9 % ( placebo ) vs 10.6 % ± 20.0 % ( VD ; P = .048 ) . CONCLUSION Vitamin D₃ supplementation increased intramyonuclear VDR concentration by 30 % and increased muscle fiber size by 10 % in older , mobility-limited , vitamin D-insufficient women . Further work is needed to determine whether the observed effect of vitamin D on fiber size is mediated by the VDR and to identify which signaling pathways are involved" ]	41189d98-06ff-11f0-808a-c43d1ab1c353
In the present meta- analysis , reductions in the risk of hip fracture with milk consumption were only observed among American adults , but not among Sc and inavian adults , possibly because milk products are more commonly fortified with vitamin D in the former population than in Sc and inavian countries . The reduction in the risk of hip fracture was also observed with yogurt consumption , which is often associated with healthy lifestyles and dietary patterns that contribute to improved bone health . Although dairy products contain bone-beneficial nutrients , the association between dairy consumption and the risk of hip fracture remains equivocal . Fueling this uncertainty , the elevated risk of hip fracture in association with milk consumption was observed in a cohort of Swedish women . A systematic review and meta- analysis of prospect i ve cohort studies was performed to critically evaluate the association , or lack thereof , between dairy consumption ( milk , yogurt , and cheese ) and the risk of hip fracture . A r and om effects model was used to generate the summary relative risks ( RRs ) with their 95 % confidence intervals ( CIs ) for the associations of interest . In the meta- analysis of the highest versus lowest category of consumption , higher consumption of yogurt ( RR 0.78 , 95 % CI 0.68 , 0.90 ) , but not milk ( RR 0.86 , 95 % CI 0.73 , 1.02 ) or cheese ( RR 0.85 , 95 % CI 0.66 , 1.08 ) , was associated with a lower risk of hip fracture . For milk , the reduced risk of fracture with higher milk consumption was observed in the USA ( RR 0.75 , 95 % CI 0.65 , 0.87 ) , but not in Sc and inavian countries ( RR 1.00 , 95 % CI 0.85 , 1.17 ) . These findings were further supported by the fact that American studies ( RR 0.93 , 95 % CI 0.88 , 0.98 ; per 1 glass/day ) , but not Sc and inavian studies ( RR 1.01 , 95 % CI 0.95 , 1.07 ; per 1 glass/day ) , demonstrated a linear association between milk consumption and the risk of hip fracture . The cumulative evidence from prospect i ve cohort studies reassuringly suggests that the risk of hip fracture may not be elevated among people who consume milk , yogurt , and cheese , and that a greater consumption of milk or yogurt may even be associated with a lower risk of hip fracture depending on the factors that may differ across the population of interest	[ "Dietary data from a prospect i ve study were used to relate factors influencing calcium balance ( estimates of dietary calcium intake , protein intake from nondairy animal sources ( meat , fish , and eggs ) , and coffee consumption ) to the incidence of hip fracture . During the years 1977 - 1983 , women and men born between 1925 and 1940 and living in one of three Norwegian counties were invited to a cardiovascular screening that included a dietary survey . The attendance rate at screening was 91.1 % , and 90.7 % of these persons ( 19,752 women and 20,035 men ) filled in and returned a semiquantitative dietary question naire . This cohort was followed for an average of 11.4 years ( range , 0.01 - 13.8 years ) with respect to hip fracture , defined as cervical or trochanteric fracture . During follow-up , 213 hip fractures were identified , excluding fractures associated with high-energy trauma and metastatic bone disease . There was no clear association between calcium intake or nondairy animal protein intake and hip fracture in this cohort . However , an elevated risk of fracture was found in women with a high intake of protein from nondairy animal sources in the presence of low calcium intake ( relative risk = 1.96 ( 95 % confidence interval 1.09 - 3.56 ) for the highest quarter of nondairy protein intake and the lowest quarter of calcium intake vs. the three lower quarters of protein intake and the three higher quarters of calcium intake ) . Women who drank nine or more cups of coffee per day also had an increased risk of fracture , while there was no association between coffee consumption and hip fracture in men . Although these findings do not necessarily imply causal relations , they suggest the presence of risk factors for hip fracture that act through a negative calcium balance in this population", "BACKGROUND The effect of meat protein on calcium retention at different calcium intakes is unresolved . OBJECTIVE The objective was to test the effect of dietary protein on calcium retention at low and high intakes of calcium . DESIGN In a r and omized controlled feeding study with a 2 x 2 factorial crossover design , healthy postmenopausal women ( n = 27 ) consumed either approximately 675 or approximately 1510 mg Ca/d , with both low and high protein ( providing 10 % and 20 % energy ) for 7 wk each , separated by a 3-wk washout period . After 3 wk , the entire diet was extrinsically labeled with (47)Ca , and isotope retention was monitored by whole-body scintillation counting . Clinical markers of calcium and bone metabolism were measured . RESULTS High compared with low dietary protein significantly increased calcium retention from the low-calcium ( 29.5 % compared with 26.0 % absorbed ) but not the high-calcium diet ( 18 % absorbed ) . For the low-calcium diet , this effect nearly balanced a protein-related 0.5-mmol/d greater urinary calcium excretion . Protein-related calciuretic effects were independent of dietary calcium . Testing at 1 , 2 , 3 , 5 , and 7 wk showed no long-term adaptation in urinary acidity or urinary calcium excretion . High compared with low dietary protein decreased urinary deoxypyridinoline and increased serum insulin-like growth factor I without affecting parathyroid hormone , osteocalcin , bone-specific alkaline phosphatase , or tartrate-resistant acid phosphatase . CONCLUSIONS In healthy postmenopausal women , a moderate increase in dietary protein , from 10 % to 20 % of energy , slightly improved calcium absorption from a low-calcium diet , nearly compensating for a slight increase in urinary calcium excretion . Under practical dietary conditions , increased dietary protein from animal sources was not detrimental to calcium balance or short-term indicators of bone health", "High dietary acid load ( DAL ) may be detrimental to bone mineral density ( BMD ) . The objectives of the study were to : ( 1 ) evaluate the cross-sectional relation between DAL and BMD ; and ( 2 ) determine whether calcium intake modifies this association . Men ( n = 1218 ) and women ( n = 907 ) aged ≥60 years were included from the National Health and Nutrition Examination Survey 2005 - 2008 . Nutrient intake from 2 , 24-hour recalls was used to calculate net endogenous acid production ( NEAP ) and potential renal acid load ( PRAL ) ( mEq/d ) . PRAL was calculated from dietary calcium ( PRALdiet ) and diet + supplemental calcium ( PRALtotal ) . Tests for linear trend in adjusted mean BMD of the hip and lumbar spine were performed across energy-adjusted NEAP and PRAL quartiles . Modification by calcium intake ( dietary or total ) above or below 800 mg/d was assessed by interaction terms . Overall , mean age was 69 ± 0.3 years . Among women , there was no association between NEAP and BMD . PRALdiet was positively associated with proximal femur BMD ( p trend = 0.04 ) . No associations were observed with PRALtotal at any BMD site ( p range , 0.38 - 0.82 ) . Among men , no significant associations were observed between BMD and NEAP or PRAL . However , an interaction between PRALdiet and calcium intake was observed with proximal femur BMD ( p = 0.08 ) . An inverse association between PRALdiet and proximal femur BMD was detected among men with dietary calcium ( p = 0.02 ) ; no associations were found among men with ≥800 mg/d ( p = 0.98 ) . A significant interaction with PRALtotal was not observed . In conclusion , when supplemental calcium is considered , there is no association between DAL and BMD among adults . Men with low dietary calcium showed an inverse relation with PRAL at the proximal femur ; in women no interaction was observed . This study highlights the importance of calcium intake in counteracting the adverse effect of DAL on bone health . Further research should determine the relation between DAL and change in BMD with very low calcium intake", "Purpose In Malaysia , hip fracture incidence is higher in Chinese women than other ethnic groups . This study compared the effects of a high-calcium vitamin D fortified milk with added FOS-inulin versus regular milk over 1 year on aspects of bone health in Chinese postmenopausal women in Malaysia . Methods One-hundred and twenty-one women ( mean age 59 ( ± 4 ) years ) were r and omized into two groups : control ( n = 60 ; regular milk , 428 mg calcium per day ) or intervention ( n = 61 ; fortified milk at 1200 mg calcium , 96 mg magnesium , 2.4 mg zinc , 15 μg vitamin D and 4 g FOS-inulin per day ) . At baseline , weeks 12 , 24 , 36 and 52 , parathyroid hormone ( PTH ) , C-Telopeptide of Type I Collagen ( CTx-1 ) , Procollagen I Intact N-Terminal propeptide ( PINP ) and vitamin D levels were assessed . Bone density ( BMD ) was measured at baseline and week 52 using a GE Lunar iDXA . Results Body mass index , lumbar spine and femoral neck BMD did not differ between groups at baseline . Over 52 weeks , mean plasma 25 ( OH ) D3 levels increased to 74.8 nmol/L ( intervention group ) or remained at 63.1 nmol/L ( control group ) ( p groups ) . PTH levels increased in the control group ( p = 0.001 ) . The intervention result ed in a significant suppression of CTx-1 and PINP at p = 0.018 and p = 0.004 . Femoral neck BMD remained stable in the intervention group but decreased significantly in the controls , with a borderline treatment effect ( p = 0.07 ) . Conclusion Compared with regular milk , the fortified milk suppressed bone turnover markers and tended to increase femoral neck BMD", "Context We hypothesize that endogenous sex steroids are associated with fracture risk independent of race/ethnicity . Design and Setting We performed a nested case-control study within the prospect i ve Women 's Health Initiative Observational Study . Incident nonspine fractures were identified in 381 black , 192 Hispanic , 112 Asian , and 46 Native American women over an average of 8.6 years . A r and om sample of 400 white women who experienced an incident fracture was chosen . One control was selected per case and matched on age , race/ethnicity , and blood draw date . Bioavailable estradiol ( BioE2 ) , bioavailable testosterone ( BioT ) , and sex hormone-binding globulin ( SHBG ) were measured using baseline fasting serum . Conditional logistic regression models calculated the odds ratio ( OR ) and 95 % confidence interval ( CI ) of fracture across tertiles of hormone . Results In multivariable and race/ethnicity-adjusted models , higher BioE2 ( > 8.25 pg/mL ) and higher BioT ( > 13.3 ng/dL ) were associated with decreased risk of fracture ( OR , 0.65 ; 95 % CI , 0.50 to 0.85 ; P trend = 0.001 and OR , 0.76 ; 95 % CI , 0.60 to 0.96 ; P trend = 0.02 , respectively ) . The interaction term between race/ethnicity and either BioE2 or BioT was not significant . There was no association between SHBG and fracture risk . In models stratifying by race/ethnicity , higher BioE2 was associated with a lower risk of fracture in both white women ( OR , 0.56 ; 95 % CI , 0.36 to 0.87 ) and black women ( OR , 0.61 ; 95 % CI , 0.39 to 0.96 ) . Higher BioT was associated with a significantly lower fracture risk in only black women ( OR , 0.65 ; 95 % CI , 0.43 to 1.00 ) , P trend = 0.03 . Conclusions Serum BioE2 and BioT are associated with fracture risk in older women irrespective of race/ethnicity and independent of established risk factors for fracture", "BACKGROUND Short trials of calcium supplementation show that it reduces loss of bone density in postmenopausal women ; longer observational studies do not generally find a lower risk of hip fracture with higher-calcium diets . Fewer studies have focused on vitamin D in preventing postmenopausal osteoporosis or fractures . OBJECTIVE We assessed relations between postmenopausal hip fracture risk and calcium , vitamin D , and milk consumption . DESIGN In an 18-y prospect i ve analysis in 72 337 postmenopausal women , dietary intake and nutritional supplement use were assessed at baseline in 1980 and up date d several times during follow-up . We identified 603 incident hip fractures result ing from low or moderate trauma . Relative risks ( RRs ) from proportional hazards models were controlled for other dietary and nondietary factors . RESULTS Women consuming > or = 12.5 microg vitamin D/d from food plus supplements had a 37 % lower risk of hip fracture ( RR = 0.63 ; 95 % CI : 0.42 , 0.94 ) than did women consuming Total calcium intake was not associated with hip fracture risk ( RR = 0.96 ; 95 % CI : 0.68 , 1.34 for > or = 1200 compared with lower risk of hip fracture ( P for trend = 0.21 ) . CONCLUSIONS An adequate vitamin D intake is associated with a lower risk of osteoporotic hip fractures in postmenopausal women . Neither milk nor a high-calcium diet appears to reduce risk . Because women commonly consume less than the recommended intake of vitamin D , supplement use or dark fish consumption may be prudent", "The aim of this study was to investigate whether a product rich in transgalactooligosaccharides ( TOS , Elix'or ) stimulates true Ca absorption in postmenopausal women . The study was a double-blind , r and omized crossover study , consisting of two 9-d treatment periods separated by a 19-d washout period . During the treatment periods , 12 subjects drank 200 mL yogurt drink twice ( at breakfast and lunch ) containing either TOS ( 20 g/d ) or the reference substance , sucrose . On d 8 of each treatment period , (44)Ca and (48)Ca were administered orally and intravenously , respectively . Before and during the 36 h after isotope administration , urine was collected and the ratios of isotopes present were measured by inductively coupled plasma mass spectrometry ( ICP-MS ) . From the isotope enrichments , true calcium absorption was calculated . TOS increased true calcium absorption 16 % , from ( mean + /- SD ) 20.6 + /- 7.0 % during the reference treatment to 23.9 + /- 6.9 % during the TOS treatment ( P : = 0.04 , one-sided ) . In conclusion , in this study in postmenopausal women , greater Ca absorption was observed after consumption of a product rich in TOS ( Elix'or ) compared with the reference treatment . This increase in Ca absorption was likely due solely to TOS . The increased Ca absorption was not accompanied by increased urinary Ca excretion , meaning that TOS also may indirectly increase the uptake of Ca by bones and /or inhibit bone resorption", "BACKGROUND In rats , nondigestible oligosaccharides stimulate calcium absorption . Recently , this effect was also found in human subjects . OBJECTIVE The objective of the study was to investigate whether consumption of 15 g oligofructose/d stimulates calcium absorption in male adolescents . DESIGN Twelve healthy , male adolescents aged 14 - 16 y received , for 9 d , 15 g oligofructose or sucrose ( control treatment ) daily over 3 main meals . The treatments were given according to a r and omized , double-blind , crossover design , separated by a 19-d washout period . On the 8th day of each treatment period , 44Ca was given orally with a st and ard breakfast containing approximately 200 mg Ca . Within half an hour after administration of 44Ca , 48Ca was administered intravenously . Fractional calcium absorption was computed from the enrichment of 44Ca:43Ca and 48Ca:43Ca in 36-h urine sample s , which was measured by inductively coupled plasma mass spectrometry . RESULTS An increase in true fractional calcium absorption ( % ) was found after consumption of oligofructose ( mean difference + /- SE of difference : 10.8+/-5.6 ; P oligofructose per day stimulates fractional calcium absorption in male adolescents", "BACKGROUND Short-term studies in adolescents have generally shown an enhancement of calcium absorption by inulin-type fructans ( prebiotics ) . Results have been inconsistent ; however , and no studies have been conducted to determine whether this effect persists with long-term use . OBJECTIVE The objective was to assess the effects on calcium absorption and bone mineral accretion after 8 wk and 1 y of supplementation with an inulin-type fructan . DESIGN Pubertal adolescents were r and omly assigned to receive 8 g/d of a mixed short and long degree of polymerization inulin-type fructan product ( fructan group ) or maltodextrin placebo ( control group ) . Bone mineral content and bone mineral density were measured before r and omization and after 1 y. Calcium absorption was measured with the use of stable isotopes at baseline and 8 wk and 1 y after supplementation . Polymorphisms of the Fok1 vitamin D receptor gene were determined . RESULTS Calcium absorption was significantly greater in the fructan group than in the control group at 8 wk ( difference : 8.5 + /- 1.6 % ; P Fok1 genotype was present such that subjects with an ff genotype had the least initial response to fructan . After 1 y , the fructan group had a greater increment in both whole-body bone mineral content ( difference : 35 + /- 16 g ; P = 0.03 ) and whole-body bone mineral density ( difference : 0.015 + /- 0.004 g/cm(2 ) ; P = 0.01 ) than did the control group . CONCLUSION Daily consumption of a combination of prebiotic short- and long-chain inulin-type fructans significantly increases calcium absorption and enhances bone mineralization during pubertal growth . Effects of dietary factors on calcium absorption may be modulated by genetic factors , including specific vitamin D receptor gene polymorphisms", "Background : Previous studies showed beneficial effects of specific dairy foods on bone health in middle-aged adults . Objective : We examined the association of milk , yogurt , cheese , cream , fluid dairy ( milk + yogurt ) , and milk + yogurt + cheese intakes with bone mineral density ( BMD ) and 4-y percentage of change in BMD [ ▵ % BMD ; femoral neck , trochanter , and lumbar spine ( LS ) ] . We further assessed whether these associations were modified by vitamin D supplement use in this cohort of older adults . Methods : Food-frequency question naire responses , baseline BMD ( hip and spine , n = 862 in 1988 - 1989 ) , and follow-up BMD ( n = 628 in 1992 - 1993 ) were measured in the Framingham study , a prospect i ve cohort study of older Caucasian men and women aged 67 - 93 y. Outcomes included baseline BMD and ▵ % BMD . Dairy-food intakes ( servings per week ) were converted to energy-adjusted residuals , and linear regression was used , adjusting for covariates . These associations were further examined by vitamin D supplement use . Results : The mean age of the participants was 75 y. In the full sample , dairy-food items were not associated with BMD ( P = 0.11 - 0.99 ) or with ▵ % BMD ( P = 0.29 - 0.96 ) . Among vitamin D supplement users , but not among nonusers , higher milk , fluid dairy , and milk + yogurt + cheese intakes were associated with higher LS BMD ( P = 0.011 - 0.009 ) . Among vitamin D supplement users , but not among nonusers , higher milk + yogurt + cheese intakes were protective against trochanter BMD loss ( P = 0.009 ) . Conclusions : In this population of older adults , higher intakes of milk , fluid dairy , and milk + yogurt + cheese were associated with higher LS BMD , and a higher intake of milk + yogurt + cheese was protective against trochanter BMD loss among vitamin D supplement users but not among nonusers . These findings underscore that the benefits of dairy intake on the skeleton may be dependent on vitamin D intake", "OBJECTIVE To determine the effect of the daily intake of calcium and vitamin D-enriched milk ( with or without fructooligosaccharides [ FOS ] ) on vitamin D , bone metabolism , and cardiovascular risk factors . MATERIAL S AND METHODS Two-year r and omized controlled study , including 500 healthy postmenopausal women , assigned to 500 mL/day of skimmed milk to one of three groups : Low-dose ( L ) : ( 120 mg/100 mL calcium , vitamin D3 30 UI/100 mL ) , group A : calcium and vitamin D ( 180 mg/100 mL and 120 UI/100 mL ) , and group B : calcium and vitamin D ( 180 mg/100 mL and 120 UI/100 mL ) and FOS ( 5 g/L ) . We evaluated serum 25(OH)D , bone mineral density ( BMD ) by Dual Energy X-ray Absorptiometry , and biochemical data of glucose and lipid metabolism . RESULTS After 24 months , vitamin D concentrations did not change in the control group , but increased in group A and group B , p femoral neck BMD and an improvement in fasting plasma glucose , HbA1c , total cholesterol , low-density lipoprotein cholesterol , and apolipoprotein B 100 . CONCLUSIONS Daily intake of milk enriched with calcium and vitamin D in postmenopausal healthy women induces a significant improvement in vitamin D status , a significant increase in BMD at femoral neck , and also favorable effects on glucose and lipid profile", "OBJECTIVE We compared the effect of supplementation with a fortified skimmed milk product ( high calcium skim milk ) with or without added phylloquinone ( vitamin K(1 ) ) on markers of bone formation and resorption in premenopausal women . METHODS Eighty-two women 20 to 35 y of age were r and omly allocated to three groups . Two groups received two daily servings of high calcium skim milk ( 1000 mg/d of extra calcium ) with or without added phylloquinone ( 80 microg/d ) for 16 wk , and a third control group received no supplementation . Bone density was assessed at baseline and the bone markers , total osteocalcin , type I N-terminal procollagen peptide , and cross-linked C-telopeptide of type I collagen were measured at baseline and at weeks 2 , 12 , and 16 . Serum phylloquinone and undercarboxylated osteocalcin were measured in the control and vitamin K-supplemented groups at weeks 0 and 16 . RESULTS Baseline values for age , body mass index , and bone density did not differ across groups . In vitamin K-supplemented women , mean serum phylloquinone concentrations increased from 0.27 to 0.76 microg/L ( P undercarboxylated osteocalcin concentrations decreased from 9.68 to 4.46 microg/L ( P Plasma cross-linked C-telopeptide of type I collagen , total osteocalcin , and type I N-terminal procollagen peptide levels decreased significantly in both supplemented groups compared with the control group over 16 wk ( cross-linked C-telopeptide of type I collagen > 30 % , total osteocalcin and type I N-terminal procollagen peptide > 15 % ) . CONCLUSION Fortified milk supplementation in premenopausal women reduced bone turnover significantly . Phylloquinone fortification substantially improved vitamin K status but had no demonstrable additive effect on bone turnover in this short-term study", "Increased postmenopausal bone turnover leads to bone loss and fragility fracture risk . In the absence of osteoporosis , risk preventive measures , particularly those modifying nutritional lifestyle , are appropriate . We tested the hypothesis that milk supplementation affects bone turnover related to biochemical markers in a direction that , in the long term , may be expected to reduce postmenopausal bone loss . Thirty healthy postmenopausal women aged 59.3 ( SD 3.3 ) years were enrolled in a prospect i ve crossover trial of 16 weeks . After a 4-week period of adaptation with diet providing 600 mg calcium plus 300 mg ingested as 250 ml semi-skimmed milk , participants were maintained during 6 weeks under the same 600 mg calcium diet and r and omized to receive either 500 ml semi-skimmed milk , thus providing a total of 1200 mg calcium , or no milk supplement . In the next 6 weeks they were switched to the alternative regimen . At the end of the each period , i.e. after 4 , 10 and 16 weeks , blood and urinary sample s were collected . The changes in blood variables between the periods of 6 weeks without and with milk supplementation were : for parathyroid hormone , -3.2 pg/ml ( P=0.0054 ) ; for crosslinked telopeptide of type I collagen , -624 pg/ml ( P propeptide of type I procollagen , -5.5 ng/ml ( P=0.0092 ) ; for osteocalcin , -2.8 ng/ml ( P=0.0014 ) . In conclusion , a 6-week period of milk supplementation induced a decrease in several biochemical variables compatible with diminished bone turnover mediated by reduction in parathyroid hormone secretion . This nutritional approach to postmenopausal alteration in bone metabolism may be a valuable measure in the primary prevention of osteoporosis", "Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load ( PRAL ) diet on calcium ( Ca ) absorption and retention and markers of bone metabolism . In a r and omized crossover design , 16 postmenopausal women consumed 2 diets : 1 with low protein and low PRAL ( LPLP ; total protein : 61 g/d ; PRAL : -48 mEq/d ) and 1 with high protein and high PRAL ( HPHP ; total protein : 118 g/d ; PRAL : 33 mEq/d ) for 7 wk each separated by a 1-wk break . Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca . Compared with the LPLP diet , the HPHP diet increased participants ' serum IGF-I concentrations ( P decreased serum intact PTH concentrations ( P increased fractional (47)Ca absorption ( mean ± pooled SD : 22.3 vs. 26.5 ± 5.4 % ; P and urinary Ca excretion ( 156 vs. 203 ± 63 mg/d ; P = 0.005 ) . The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods ( 55 vs. 28 ± 51 mg/d ) . The dietary treatments did not affect other markers of bone metabolism . In summary , a diet high in protein and PRAL increases the fractional absorption of dietary Ca , which partially compensates for increased urinary Ca , in postmenopausal women . The increased IGF-I and decreased PTH concentrations in serum , with no change in biomarkers of bone resorption or formation , indicate a high-protein diet has no adverse effects on bone health", "PURPOSE We aim ed to determine whether women consuming fat-free milk versus isoenergetic carbohydrate after resistance exercise would see augmented gains in lean mass and reductions in fat mass similar to what we observed in young men . METHODS Young women were r and omized to drink either fat-free milk ( MILK : n = 10 ; age ( mean + /- SD ) = 23.2 + /- 2.8 yr ; BMI = 26.2 + /- 4.2 kg x m(-2 ) ) or isoenergetic carbohydrate ( CON : n = 10 ; age = 22.4 + /- 2.4 yr ; BMI = 25.2 + /- 3.8 kg x m(-2 ) ) immediately after and 1 h after exercise ( 2 x 500 mL ) . Subjects exercised 5 d x wk(-1 ) for 12 wk . Body composition changes were measured by dual-energy x-ray absorptiometry , and subjects ' strength and fasting blood were measured before and after training . RESULTS CON gained weight after training ( CON : + 0.86 + /- 0.4 kg , P Lean mass increased with training in both groups ( P Fat mass decreased with training in MILK only ( -1.6 + /- 0.4 kg , P Isotonic strength increased more in MILK than CON ( P Serum 25-hydroxyvitamin D increased in both groups but to a greater extent in MILK than CON ( + 6.5 + /- 1.1 vs + 2.8 + /- 1.3 nM , respectively , P parathyroid hormone decreased only in MILK ( -1.2 + /- 0.2 pM , P muscle mass accretion , strength gains , fat mass loss , and a possible reduction in bone turnover in women after 12 wk . Our results , similar to those in men , highlight that milk is an effective drink to support favorable body composition changes in women with resistance training", "Non-digestible oligosaccharides such as inulin and oligofructose have been shown to consistently increase calcium absorption in experimental animals , but data in humans are less clear-cut . The objective of this study was to assess the effect of 8 g/d of oligofructose or a mixture of inulin and oligofructose on calcium absorption in girls at or near menarche . A total of fifty-nine subjects were studied using a balanced , r and omized , cross-over design . They received , in r and om order , 8 g/d placebo ( sucrose ) , oligofructose or the mixture inulin+oligofructose for 3 weeks , separated by a 2-week washout period . Throughout the study , subjects consumed a total of approximately 1500 mg/d dietary calcium , by adding two glasses of calcium-fortified orange juice to their diet . Four grams of placebo , oligofructose or the mixture inulin+oligofructose was added to each glass of orange juice immediately before it was consumed . At the end of each 3-week adaptation period , calcium absorption was measured , using a dual stable isotope technique , from the cumulative fractional excretion of an oral and an intravenous tracer over 48 hours . Calcium absorption was significantly higher in the group receiving the inulin+oligofructose mixture than in the placebo group v. P=0.01 ) , but no significant difference was seen between the oligofructose group and the placebo group v. P = NS ) . We conclude that modest intakes of an inulin+oligofructose mixture increases calcium absorption in girls at or near menarche", "Background The acid-ash hypothesis , the alkaline diet , and related products are marketed to the general public . Websites , lay literature , and direct mail marketing encourage people to measure their urine pH to assess their health status and their risk of osteoporosis . The objectives of this study were to determine whether 1 ) low urine pH , or 2 ) acid excretion in urine [ sulfate + chloride + 1.8x phosphate + organic acids ] minus [ sodium + potassium + 2x calcium + 2x magnesium mEq ] in fasting morning urine predict : a ) fragility fractures ; and b ) five-year change of bone mineral density ( BMD ) in adults . Methods Design : Cohort study : the prospect i ve population -based Canadian Multicentre Osteoporosis Study . Multiple logistic regression was used to examine associations between acid excretion ( urine pH and urine acid excretion ) in fasting morning with the incidence of fractures ( 6804 person years ) . Multiple linear regression was used to examine associations between acid excretion with changes in BMD over 5-years at three sites : lumbar spine , femoral neck , and total hip ( n = 651 ) . Potential confounders controlled included : age , gender , family history of osteoporosis , physical activity , smoking , calcium intake , vitamin D status , estrogen status , medications , renal function , urine creatinine , body mass index , and change of body mass index . Results There were no associations between either urine pH or acid excretion and either the incidence of fractures or change of BMD after adjustment for confounders . Conclusion Urine pH and urine acid excretion do not predict osteoporosis risk", "Excess dietary proteins and \" acid ash \" diets have been suspected to increase the risk of osteoporosis , but experimental and epidemiological evidence is mixed . We aim ed to determine whether the association between protein intake and the overall acid-base equilibrium of the diet ( as renal net acid excretion [ RNAE ] estimate ) and fracture risk vary according to calcium intake . During an average of 8.37 + /- 1.73 yr of follow-up , 2408 women reported a fracture ( excluding high-impact trauma ) among 36,217 postmenopausal women from the E3N prospect i ve study . We used Cox regression models to study the interaction between calcium and , respectively , proteins and RNAE , from the 1993 dietary question naire for fracture risk determination , adjusting for potential confounders . There was no overall association between fracture risk and total protein or RNAE . However , in the lowest quartile of calcium ( fracture risk ( RR = 1.51 for highest versus lowest quartile ; 95 % CI , 1.17 - 1.94 ) . An increasing fracture risk with increasing animal protein intake was also observed ( trend , p interaction for fracture risk was observed between RNAE and calcium . In this Western population of postmenopausal women with normal to high protein intake and fairly high calcium intake , there was no overall association between total protein or RNAE and fracture risk . However , there was some evidence that high protein-high acid ash diets were associated with an increased risk of fracture when calcium intake was low ( < 400 mg/1000 kcal )", "Summary A longitudinal analysis of bone microstructure in postmenopausal women of the Geneva Retirees Cohort indicates that age-related cortical bone loss is attenuated at non-bearing bone sites in fermented dairy products consumers , not in milk or ripened cheese consumers , independently of total energy , calcium , or protein intakes . Introduction Fermented dairy products ( FDP ) , including yogurts , provide calcium , phosphorus , and proteins together with prebiotics and probiotics , all being potentially beneficial for bone . In this prospect i ve cohort study , we investigated whether FDP , milk , or ripened cheese consumptions influence age-related changes of bone mineral density ( BMD ) and microstructure . Methods Dietary intakes were assessed at baseline and after 3.0 ± 0.5 years with a food frequency question naire in 482 postmenopausal women enrolled in the Geneva Retirees Cohort . Cortical ( Ct ) and trabecular ( Tb ) volumetric ( v ) BMD and microstructure at the distal radius and tibia were assessed by high-resolution peripheral quantitative computerized tomography , in addition to areal ( a ) BMD and body composition by dual-energy X-ray absorptiometry , at the same time points . Results At baseline , FDP consumers had lower abdominal fat mass and larger bone size at the radius and tibia . Parathyroid hormone and β-carboxyterminal cross-linked telopeptide of type I collagen levels were inversely correlated with FDP consumption . In the longitudinal analysis , FDP consumption ( mean of the two assessment s ) was associated with attenuated loss of radius total vBMD and of Ct vBMD , area , and thickness . There was no difference in aBMD and at the tibia . These associations were independent of total energy , calcium , or protein intakes . For other dairy products categories , only milk consumption was associated with lower decrease of aBMD and of failure load at the radius . Conclusion In this prospect i ve cohort of healthy postmenopausal women , age-related Ct bone loss was attenuated at non-bearing bone sites in FDP consumers , not in milk or ripened cheese consumers , independently of total energy , calcium , or protein intakes . Study registration IS RCT N11865958 ( http://www.is rct n.com", "Dairy foods are rich in bone-beneficial nutrients , yet the role of dairy foods in hip fracture prevention remains controversial . Our objective was to evaluate the association of milk , yogurt , cheese , cream , and milk + yogurt intakes with incident hip fracture in the Framingham Original Cohort . A total of 830 men and women from the Framingham Original Cohort , a prospect i ve cohort study , completed a food-frequency question naire ( 1988 to 1989 ) and were followed for hip fracture until 2008 . In this population -based study , Cox-proportional hazards regression was used to estimate hazard ratios ( HR ) by categories of energy-adjusted dairy intake ( servings/wk ) , adjusting for st and ard confounders and covariates . The exposure was energy-adjusted intakes of milk , yogurt , cheese , cream , and milk + yogurt ( servings/wk ) . Risk of hip fracture over the follow-up was the primary outcome ; the hypothesis being tested was formulated after data collection . The mean age at baseline was 77 years ( SD 4.9 , range 68 to 96 ) . Ninety-seven hip fractures occurred over the mean follow-up time of 11.6 years ( range 0.04 to 21.9 years ) . The mean ± SD ( servings/wk ) of dairy intakes at baseline were : milk = 6.0 ± 6.4 ; yogurt = 0.4 ± 1.3 ; cheese = 2.6 ± 3.1 ; and cream = 3.4 ± 5.5 . Participants with medium ( > 1 and lower hip fracture risk than those with low ( ≤1 serving/wk ) intake ( high versus low intake HR 0.58 , 95 % confidence interval [ CI ] 0.31 - 1.06 , p = 0.078 ; medium versus low intake HR 0.61 , 95 % CI 0.36 - 1.08 , p = 0.071 ; p trend = 0.178 ] . There appeared to be a threshold for milk , with 40 % lower risk of hip fracture among those with medium/high milk intake compared with those with low intake ( p = 0.061 ) . A similar threshold was observed for milk + yogurt intake ( p = 0.104 ) . These associations were further attenuated after adjustment for femoral neck bone mineral density . No significant associations were seen for other dairy foods ( p range = 0.117 to 0.746 ) . These results suggest that greater intakes of milk and milk + yogurt may lower risk for hip fracture in older adults through mechanisms that are partially , but not entirely , attributable to effects on bone mineral density", "Although high-protein diets induce hypercalciuria in humans , the source of the additional urinary calcium remains unclear . One hypothesis is that the high endogenous acid load of a high-protein diet is partially buffered by bone , leading to increased skeletal resorption and hypercalciuria . We used dual stable calcium isotopes to quantify the effect of a high-protein diet on calcium kinetics in women . The study consisted of 2 wk of a lead-in , well-balanced diet followed by 10 d of an experimental diet containing either moderate ( 1.0 g/kg ) or high ( 2.1 g/kg ) protein . Thirteen healthy women received both levels of protein in r and om order . Intestinal calcium absorption increased during the high-protein diet in comparison with the moderate ( 26.2 + /- 1.9 % vs. 18.5 + /- 1.6 % , P urinary calcium ( 5.23 + /- 0.37 vs. 3.57 + /- 0.35 mmol/d , P fraction of urinary calcium of bone origin and a nonsignificant trend toward a reduction in the rate of bone turnover . There were no protein-induced effects on net bone balance . These data directly demonstrate that , at least in the short term , high-protein diets are not detrimental to bone", "The long-term effects of calcium and vitamin D supplementation on bone material and structural properties in older men are not known . The aim of this study was to examine the effects of high calcium ( 1000 mg/day)- and vitamin-D(3 ) ( 800 IU/day)-fortified milk on cortical and trabecular volumetric BMD ( vBMD ) and bone geometry at the axial and appendicular skeleton in men aged over 50 years . One hundred and eleven men who were part of a larger 2-year r and omized controlled trial had QCT scans of the mid-femur and lumbar spine ( L(1)-L(3 ) ) to assess vBMD , bone geometry and indices of bone strength [ polar moment of inertia ( I(polar ) ) ] . After 2 years , there were no significant differences between the milk supplementation and control group for the change in any mid-femur or L(1)-L(3 ) bone parameters for all men aged over 50 years . However , the mid-femur skeletal responses to the fortified milk varied according to age , with a split of 62 years being the most significant for discriminating the changes between the two groups . Subsequent analysis revealed that , in the older men ( > 62 years ) , the expansion in mid-femur medullary area was 2.8 % ( P milk supplementation compared to control group , which helped to preserve cortical area in the milk supplementation group ( between group difference 1.1 % , P mid-femur cortical vBMD and I(polar ) , the net loss was 2.3 and 2.8 % less in the milk supplementation compared to control group ( P calcium-vitamin-D(3)-fortified milk may represent an effective strategy to maintain bone strength by preventing endocortical bone loss and slowing the loss in cortical vBMD in elderly men", "ABSTRACT Objective : The development of alternative approaches to prevent and /or treat osteoporosis , as a chronic progressive bone disease , is being considered currently . Among dietary supplements , probiotics may have favorable effects on bone metabolism . Therefore , the aim of this study was to evaluate the effects of a multispecies probiotic supplementation on bone biomarkers and bone density in osteopenic postmenopausal women . Methods : This r and omized double-blind placebo-controlled clinical trial was performed on 50 patients with osteopenia aged 50–72 years . Participants were r and omly assigned to take either a multispecies probiotic supplement ( GeriLact ; n = 25 ) or placebo ( n = 25 ) for 6 months . GeriLact contains 7 probiotic bacteria species . Participants received 500 mg Ca plus 200 IU vitamin D daily . Bone mineral density ( BMD ) of lumbar spine and total hip and blood biomarkers including bone-specific alkaline phosphatase ( BALP ) , osteocalcin ( OC ) , collagen type 1 cross-linked C-telopeptide ( CTX ) , deoxypyridinoline ( DPD ) , parathyroid hormone ( PTH ) , 25-OH vitamin D , and serum pro-inflammatory cytokines ( tumor necrosis factor [TNF]-α and interleukin [IL]-1β ) were assessed at baseline and at the end of the study . Results : The multispecies probiotic significantly decreased BALP ( p = 0.03 ) and CTX ( p = 0.04 ) levels in comparison with the control group but had no effect on BMD of the spine and total hip . Moreover , there was a statistically significant decrease in serum PTH ( p = 0.01 ) and TNF-α ( p = 0.02 ) in the intervention group compared to the placebo group . Conclusions : These results may suggest the favorable effects of the multispecies probiotic supplementation for 6 months on bone health in postmenopausal women due to slowing down the rate of bone turnover ", "The etiologic role of dietary calcium and vitamin D intake in primary prevention of osteoporotic fractures is uncertain , despite considerable research efforts . With the aim to examine these associations with an improved precision , we used data from a large population -based prospect i ve cohort study in central Sweden . We estimated nutrient intake from a self-administered food-frequency question naire filled in by 60,689 women , aged 40 - 74 years at baseline during 1987 - 1990 . During follow-up , we observed 3986 women with a fracture at any site and 1535 with a hip fracture . Rate ratio of fractures ( RR ) and 95 % CI were estimated using Cox proportional hazards models . We found no dose-response association between dietary calcium intake and fracture risk . The age-adjusted RR of hip fracture was 1.01 ( 95 % CI 0.96 - 1.06 ) per 300 mg calcium/day and the corresponding risk of any osteoporotic fracture was 0.99 ( 95 % CI 0.96 - 1.03 ) . Furthermore , women with an estimated calcium intake below 400 mg/day and those with a calcium intake higher than 1200 mg/day both had a similar age-adjusted hip fracture risk as those with intermediate calcium intakes : RR 1.07 ( 95 % CI 0.92 - 1.24 ) and RR 1.00 ( 95 % CI 0.79 - 1.27 ) , respectively . Vitamin D intake was not associated with fracture risk . Furthermore , women in the highest quintiles compared to the lowest quintiles of both calcium and vitamin D intake had an age-adjusted RR of 1.02 for all fractures ( 95 % CI 0.88 - 1.17 ) . Dietary calcium or vitamin D intakes estimated at middle and older age do not seem to be of major importance for the primary prevention of osteoporotic fractures in women", "IMPORTANCE Milk consumption during adolescence is recommended to promote peak bone mass and thereby reduce fracture risk in later life . However , its role in hip fracture prevention is not established and high consumption may adversely influence risk by increasing height . OBJECTIVES To determine whether milk consumption during teenage years influences risk of hip fracture in older adults and to investigate the role of attained height in this association . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study over 22 years of follow-up in more than 96,000 white postmenopausal women from the Nurses ' Health Study and men aged 50 years and older from the Health Professionals Follow-up Study in the United States . EXPOSURES Frequency of consumption of milk and other foods during ages 13 to 18 years and attained height were reported at baseline . Current diet , weight , smoking , physical activity , medication use , and other risk factors for hip fractures were reported on biennial question naires . MAIN OUTCOMES AND MEASURES Cox proportional hazards models were used to calculate relative risks ( RRs ) of first incidence of hip fracture from low-trauma events per glass ( 8 fl oz or 240 mL ) of milk consumed per day during teenage years . RESULTS During follow-up , 1226 hip fractures were identified in women and 490 in men . After controlling for known risk factors and current milk consumption , each additional glass of milk per day during teenage years was associated with a significant 9 % higher risk of hip fracture in men ( RR = 1.09 ; 95 % CI , 1.01 - 1.17 ) . The association was attenuated when height was added to the model ( RR = 1.06 ; 95 % CI , 0.98 - 1.14 ) . Teenage milk consumption was not associated with hip fractures in women ( RR = 1.00 per glass per day ; 95 % CI , 0.95 - 1.05 ) . CONCLUSIONS AND RELEVANCE Greater milk consumption during teenage years was not associated with a lower risk of hip fracture in older adults . The positive association observed in men was partially mediated through attained height", "BACKGROUND The importance of the gut microbiome for bone metabolism in mice has recently been demonstrated , but no studies are available in humans . Lactobacillus reuteri ATCCPTA 6475 ( L. reuteri 6475 ) has been reported to increase bone mineral density ( BMD ) in mice but its effect on the human skeleton is unknown . The objective of this trial was to investigate if L. reuteri 6475 affects bone loss in older women with low BMD . METHODS In this double-blind , placebo-controlled study , women from the population who were 75 to 80 years old and had low BMD were r and omized to orally receive 1010 colony-forming units of L. reuteri 6475 daily or placebo . The predefined primary end-point was relative change after 12 months in tibia total volumetric BMD ( vBMD ) . RESULTS Ninety women were included and 70 completed the study . L. reuteri 6475 reduced loss of total vBMD compared to placebo both in the intention-to-treat ( ITT ) analysis [ -0.83 % ( 95 % confidence interval [ CI ] , -1.47 to -0.19 % ) vs. -1.85 % ( 95 % CI , -2.64 to -1.07 % ) ; mean difference 1.02 % ( 95 % CI , 0.02 - 2.03 ) ] and per protocol analysis [ -0.93 % ( 95 % CI , -1.45 to -0.40 ) vs. -1.86 % ( 95 % CI , -2.35 to -1.36 ) ; mean difference 0.93 % ( 95 % CI , 0.21 - 1.65 ) ] . In general , similar but smaller effects were observed in the secondary bone variable outcomes , but these differences did not reach statistical significance in the ITT population . Adverse events did not differ between groups . CONCLUSIONS Supplementation with L. reuteri 6475 should be further explored as a novel approach to prevent age-associated bone loss and osteoporosis", "Background Controversy has emerged about the benefits compared with harms of dairy fat , including concerns over long-term effects . Previous observational studies have assessed self-reported estimates of consumption or a single biomarker measure at baseline , which may lead to suboptimal estimation of true risk . Objective The aim of this study was to investigate prospect i ve associations of serial measures of plasma phospholipid fatty acids pentadecanoic ( 15:0 ) , heptadecanoic ( 17:0 ) , and trans-palmitoleic ( trans-16:1n-7 ) acids with total mortality , cause-specific mortality , and cardiovascular disease ( CVD ) risk among older adults . Design Among 2907 US adults aged ≥65 y and free of CVD at baseline , circulating fatty acid concentrations were measured serially at baseline , 6 y , and 13 y. Deaths and CVD events were assessed and adjudicated central ly . Prospect i ve associations were assessed by multivariate-adjusted Cox models incorporating time-dependent exposures and covariates . Results During 22 y of follow-up , 2428 deaths occurred , including 833 from CVD , 1595 from non-CVD causes , and 1301 incident CVD events . In multivariable models , circulating pentadecanoic , heptadecanoic , and trans-palmitoleic acids were not significantly associated with total mortality , with extreme-quintile HRs of 1.05 for pentadecanoic ( 95 % CI : 0.91 , 1.22 ) , 1.07 for heptadecanoic ( 95 % CI : 0.93 , 1.23 ) , and 1.05 for trans-palmitoleic ( 95 % CI : 0.91 , 1.20 ) acids . Circulating heptadecanoic acid was associated with lower CVD mortality ( extreme-quintile HR : 0.77 ; 95 % CI : 0.61 , 0.98 ) , especially stroke mortality , with a 42 % lower risk when comparing extreme quintiles of heptadecanoic acid concentrations ( HR : 0.58 ; 95 % CI : 0.35 , 0.97 ) . In contrast , heptadecanoic acid was associated with a higher risk of non-CVD mortality ( HR : 1.27 ; 95 % CI : 1.07 , 1.52 ) , which was not clearly related to any single subtype of non-CVD death . No significant associations of pentadecanoic , heptadecanoic , or trans-palmitoleic acids were seen for total incident CVD , coronary heart disease , or stroke . Conclusions Long-term exposure to circulating phospholipid pentadecanoic , heptadecanoic , or trans-palmitoleic acids was not significantly associated with total mortality or incident CVD among older adults . High circulating heptadecanoic acid was inversely associated with CVD and stroke mortality and potentially associated with higher risk of non-CVD death" ]	41189dd4-06ff-11f0-808a-c43d1ab1c353
Opinion StatementThere are 34 studies in almost 2 million participants that have reported on the association between proton pump inhibitor ( PPI ) therapy and risk of fracture . There is substantial variation between the results of each study but systematic review s of the data suggest overall there is an association between PPI therapy and risk of fracture . The magnitude of the association is modest and is most likely due to confounding factors as patients prescribed PPI therapy tend to be more frail with more risk factors for fractures than those not given these drugs . There is no clear dose – response relationship and there is no association between PPI therapy and risk of fracture in those at highest risk . Finally , there is no clear mechanism through which PPI therapy increases the risk of fracture , as recent r and omized trials show no impact of PPI therapy on calcium absorption and there is no association between PPI therapy and risk of osteoporosis . We therefore feel there is insufficient evidence to change PPI prescribing habits based on risk of fracture . Similarly , we do not recommend bone mineral density investigations for patients taking PPI therapy other than would be normally indicated . There is no evidence to support prescription of calcium and /or vitamin D in patients simply because they are taking PPI therapy . As with all medications , we only recommend prescribing PPI therapy when there is a clear indication that benefit will outweigh risk and at the lowest effective dose . Patients should be regularly assessed as to whether acid suppression is still required	[ "Proton pump inhibitors ( PPIs ) increase osteoporotic fracture risk presumably via hypochlorhydria and consequent reduced fractional calcium absorption ( FCA ) . Existing studies provide conflicting information regarding the direct effects of PPIs on FCA . We evaluated the effect of PPI therapy on FCA . We recruited women at least 5 years past menopause who were not taking acid suppressants . Participants underwent three 24-hour inpatient FCA studies using the dual stable isotope method . Two FCA studies were performed 1 month apart to establish baseline calcium absorption . The third study occurred after taking omeprazole ( 40 mg/day ) for 30 days . Each participant consumed the same foods during all FCA studies ; study meals replicated subjects ' dietary habits based on 7-day diet diaries . Twenty-one postmenopausal women ages 58 ± 7 years ( mean ± SD ) completed all study visits . Seventeen women were white , and 2 each were black and Hispanic . FCA ( mean ± SD ) was 20 % ± 10 % at visit 1 , 18 % ± 10 % at visit 2 , and 23 % ± 10 % following 30 ± 3 days of daily omeprazole ( p = .07 , ANOVA ) . Multiple linear regression revealed that age , gastric pH , serum omeprazole levels , adherence to omeprazole , and 25-hydroxyvitamin D levels were unrelated to changes in FCA between study visits 2 and 3 . The 1,25-dihydroxyvitamin D3 level at visit 2 was the only variable ( p = .049 ) associated with the change in FCA between visits 2 and 3 . PPI-associated hypochlorhydria does not decrease FCA following 30 days of continuous use . Future studies should focus on identifying mechanisms by which PPIs increase the risk of osteoporotic fracture . © 2010 American Society for Bone and Mineral Research", "This study was performed to investigate the effects of the co-administration of proton pump inhibitor ( PPI ) on the efficacy of bisphosphonate ( BP ) treatment for osteoporosis . A total of 180 women with low bone mineral density were r and omly divided into four groups , one in which sodium risedronate was administered with sodium rabeprazole and one in which only risedronate was administered ( BP + PPI and BP groups , respectively ) . The biomarkers were measured at the baseline and every 3 months , inlcuding : N-terminal telopeptide of type I collagen corrected for creatinine , bone-specific alkaline phosphatase ( BAP ) , parathyroid hormone , bone mineral density ( BMD ) of the lumbar spine and physical parameters evaluated according to the SF-36v2 ™ Health Survey . Statistical comparisons of these parameters were performed after 9 months . Data were available for a total of 137 patients ( 62 in the BP group and 75 in the BP + PPI group ) . The Δ % value of increase in BMD and improvement of physical functioning in the BP + PPI group were significantly larger , and its decrease in BAP in the BP + PPI group was significantly smaller than that in the BP group . It is expected that risedronate administration in combination with a PPI may be more effective not only for treating osteoporosis but also improving physical fitness than treatment with risedronate alone", "We studied the effect of proton pump inhibitors , histamine H2 receptor antagonists , and other types of antacid drugs on fracture risk . All cases were subjects with any fracture sustained during the year 2000 ( n = 124,655 ) . For each case , three controls ( n = 373,962 ) matched on age and gender were r and omly drawn from the background population . The primary exposure variables were use of proton pump inhibitors , histamine H2 antagonists , and other antacid drugs . Adjustments were made for several confounders , including diagnosis of an ulcer , nonsteroidal anti-inflammatory drug use , use of histamine H1 antagonists , stomach resection , previous fracture , and use of corticosteroids . The effect of dose was examined by stratifying for cumulated dose ( defined daily dose ) . Use of proton pump inhibitors was associated with an increase in fracture risk for use within the last year [ odds ratio ( OR ) = 1.18 , 95 % confidence interval ( CI ) 1.12–1.43 for overall fracture risk ; OR = 1.45 , 95 % CI 1.28–1.65 for hip fractures ; and OR = 1.60 , 95 % CI 1.25–2.04 for spine fractures ) . Histamine H2 antagonists were associated with a decreased fracture risk if they had been used within the last year ( OR = 0.88 , 95 % CI 0.82–0.95 for any fracture , OR = 0.69 , 95 % CI 0.57–0.84 for hip fractures ) . Other antacids were not associated with overall fracture risk but were associated with hip and spine fractures . Proton pump inhibitors appeared to be associated with a limited increase in fracture risk , in contrast to histamine H2 antagonists , which seemed to be associated with a small decrease in fracture risk . In all cases , the changes in risk estimates were small and the clinical significance was limited", "There has been recent media attention to the possibility that long-term proton pump inhibitor ( PPI ) prescribing may be linked to an increased risk of hip fracture according to data from the United Kingdom ( UK ) ( 1 ) and Canada ( 2 ) . The Canadian Association of Gastroenterology has prepared the following position statement on the association between PPI therapy and hip fracture in light of this evidence . The present position statement is outlined in greater detail elsewhere ( 3 ) . Yang et al ( 1 ) reported a nested case-control study using the UK General Practice Research Data base that selected patients older than 50 years of age with an incident hip fracture , and age and sex-matched controls . There were 13,556 hip fracture cases and 135,386 controls ; PPI therapy for more than one year was associated with an increased risk of hip fracture ( adjusted OR 1.44 ; 95 % CI 1.30 to 1.59 ) . Targownik et al ( 2 ) reported a further nested case-control study using the Manitoba Population Health Research Data Repository , in which 15,792 patients with osteoporosis-related fractures were compared with 47,289 controls . There was no overall association between PPI use and fracture until after five or more years of exposure , when the risk of osteoporotic fracture became significant ( adjusted OR 1.62 ; 95 % CI 1.02 to 2.58 ) . Similarly , the risk of hip fracture became significant after seven years of PPI exposure ( adjusted OR 4.55 ; 95 % CI 1.68 to 12.29 ) . The clinical significance of this is uncertain because extrapolation of these figures ( assuming 1.8 per 1000 patients develop a hip fracture [ 1 ] ) suggests that 1263 patients need to be treated with a PPI for more than one year to develop one excess hip fracture , although the number needed to harm may be much lower after seven years according to the Canadian study . These studies use reputable data bases and are rigorously conducted and analyzed appropriately . The discussion s in both of these articles suggest quite strongly that the association they have found is likely to be causal . Large data bases provide a wonderful opportunity to evaluate benefits and harms of medical interventions , but caution must be exercised before assuming the latest finding represents a risk to patients . The ready availability of data bases means that literally millions of associations can be tested ; even within a particular hypothesis there are a variety of approaches to splitting the data ( eg , duration of therapy , therapy dose , length of follow-up , patient age , male versus female ) . Research ers and journals are prone to emphasize positive findings and tend to underplay the role of chance or confounding factors . These issues are less likely to be important if a consistent association is found . An accompanying editorial ( 4 ) to the Canadian study also cites a third Danish data base study ( 5 ) that supports an association between PPI therapy and fracture . It is interesting to note that the Danish study had a much greater number of cases ( 124,655 ) than the other two studies , and yet had much more muted conclusions and was published in a lower impact factor journal . The Danish study was circumspect in their conclusions because there were inconsistencies in the data and there was no dose response information . For example , there seemed to be an increased risk with taking less than 25 doses of a PPI in one year with a lower ( but still statistically significant ) risk in those taking one dose per day for a year . There seemed to be no biologically plausible hypothesis why such infrequent use of PPI therapy would be associated with an increased risk of fracture . There were also inconsistencies with the UK and Canadian studies . The UK study reported an increased risk of hip fracture after one year of PPI therapy ; there seemed to be little increase in risk over the next four years , whereas the Canadian study only found a significant association after seven years . Targownik et al ( 2 ) suggest that perhaps the UK data base included patients that had in fact been taking PPIs for much longer ; however , this is speculation . Furthermore , a Canadian cohort study ( 6 ) followed-up on elderly patients in Ontario on warfarin ( n=52,701 ) , thyroid replacement ( n=40,555 ) , oral corticosteroid ( n=43,915 ) and PPI therapy ( n=60,383 ) for five years . There was no increased risk of hip fracture in those taking warfarin compared with those on PPI therapy ( adjusted OR 0.94 ; 95 % CI 0.81 to 1.09 ) , but there was an increased risk with corticosteroid therapy compared with PPI therapy ( adjusted OR 1.44 ; 95 % CI 1.21 to 1.70 ) . It could be that warfarin is also associated with an increased risk of hip fracture ; however , it is interesting that Targownik et al ( 2 ) found little increase in fracture risk in those taking anticoagulants ( 14.5 % of fracture cases taking anticoagulants compared with 13.4 % of controls ) . The CAG is proud to acknowledge its Benefactor Corporate Sponsors : Abbott Canada AstraZeneca Canada Inc Axcan Pharma Inc Olympus Canada Inc Pentax Canada Inc. Procter & Gamble Pharmaceuticals Schering-Plough Canada Inc. UCB Pharma Inc. Finally , there is the issue of biological plausibility . It has been proposed that acid suppression may reduce calcium absorption and increase the risk of fracture ( 1 ) . The role of pH in calcium absorption is , however , controversial . The dissolution of calcium carbonate is pH-dependent in vitro , although the clinical significance of this is uncertain given that calcium is absorbed in the small intestine where the pH is nonacidic regardless of stomach pH. A review of the literature ( 7 ) identified seven r and omized trials that evaluated calcium absorption with acid suppression in healthy subjects or those with ulcer disease . There were major method ological issues with many of the studies and they were all small . Four studies found no impact on calcium absorption while three reported decreased absorption . Further work is needed in this area , but there are no conclusive data that would make the association between fracture and PPI biologically plausible . Furthermore , some research suggests that PPI therapy may inhibit bone resorption ( 8) , which may protect against fracture risk . PPIs are one of the most well-tolerated classes of drugs on the market . They have also improved the quality of life of countless patients with acid-related disease . There are risks in prescribing any drug and this should be borne in mind by all prescribing clinicians . PPI therapy should only be prescribed for indications where there is a proven or likely benefit and the need for these drugs should be review ed on a regular basis . This applies particularly to frail and elderly patients with multiple comorbidities and those taking a number of different medications where the possibility for drug interactions increases . This message applies to all the drugs clinicians prescribe including PPI therapy . Current data would not support particular care in prescribing PPI therapy due to concerns about the risk of hip fracture . There is no persuasive evidence that the association is causal , although this can never be excluded as a possibility . The Canadian Association of Gastroenterology encourages health professionals to keep continually up date d on the medical literature and will endeavour to disseminate further guidance if more information on the possible harms of PPI therapy becomes available", "Patients with gastroesophageal reflux disease ( GERD ) receive long-term therapy with proton pump inhibitor ( PPI ) agents . Several studies have recently been published suggesting that treatment with PPI may cause bone fractures , although the number of prospect i ve studies in this regard is limited . The aim of this study is to prospect ively investigate the effect of PPIs on bone density . Between March 2009 and January 2011 , 114 GERD patients ( 18–56 years ) and 110 healthy controls were included in the present study . Bone mineral densitometry ( BMD ) by using dual-energy X-ray absorptiometry was assessed at lumbar spine and femur neck . BMD measurements were performed on all subjects at the beginning of the study . The patients were divided according to three drugs by their treatment with esomeprazole , lansoprazole , or pantoprazole . The study group was followed for at least 6 months on PPI therapy , and then BMD measurements were repeated . The mean duration of treatment with PPIs was 8.5 ± 2.3 months . In patients receiving PPIs , the mean reduction in total vertebra T score following treatment compared to pre-treatment values was 00.23 ± 0.42 units ( 95 % CI 0.15–0.30 ) ( p mean reduction in the femur T score was 0.10 ± 0.40 units ( 95 % CI 0.03–0.18 ) ( p = 0.03 ) . Reduction following treatment in L4 and total vertebra T scores of lansoprazole group was significantly higher than of pantoprazole group ( p = 0.04 ) . Reduction in femur T score of esomeprazole group was higher than of lansoprazole group and pantroprazole group , but it is not statistically significant . Treatment with a PPI results in a significant reduction in bone density . Close monitoring is beneficial for patients who are to receive long-term treatment with PPI", "Proton pump inhibitors are taken by millions of patients for prevention and treatment of gastroesophageal diseases . Case-control studies have suggested that use of omeprazole is associated with an increased risk of hip fractures . The aim of this prospect i ve study was to assess the risk of vertebral fractures in postmenopausal women using omeprazole . We studied 1,211 postmenopausal women enrolled in the Osteoporosis and Ultrasound Study from the general population . Information on omeprazole and other risk factors for fractures including prevalent fractures and bone mineral density was obtained at baseline . Vertebral fractures were assessed on X-rays obtained at baseline and at the end of the 6-year follow-up and analyzed central ly . At baseline , 5 % of this population was using omeprazole . Age-adjusted rates for vertebral fractures were 1.89 and 0.60 for 100 person-years for omeprazole users and nonusers , respectively ( P = 0.009 ) . In the multivariate analysis , omeprazole use was a significant and independent predictor of vertebral fractures ( RR = 3.50 , 95 % CI 1.14–8.44 ) . The other predictors were age higher than 65 years ( RR = 2.34 , 95 % CI 1.02–5.34 ) , prevalent vertebral fractures ( RR = 3.62 , 95 % CI 1.63–8.08 ) , and lumbar spine T score ≤ −2.5 ( RR = 2.38 , 95 % CI 1.03–5.49 ) . Omeprazole use is associated with an increased risk of vertebral fractures in postmenopausal women . Further studies are required to determine the mechanism of the association between the underlying gastric disease , omeprazole use , and risk of osteoporotic fractures ", "Objective To examine the association between chronic use of proton pump inhibitors ( PPIs ) and risk of hip fracture . Design Prospect i ve cohort study . Setting Nurses ’ Health Study , which originally recruited from the 11 most populous states in the US . Participants 79 899 postmenopausal women enrolled in the Nurses ’ Health Study who provided data on the use of PPIs and other risk factors biennially since 2000 and were followed up to 1 June 2008 . Main outcome measure Incident hip fracture Results During 565 786 person years of follow-up , we documented 893 incident hip fractures . The absolute risk of hip fracture among regular users of PPIs was 2.02 events per 1000 person years , compared with 1.51 events per 1000 person years among non-users . Compared with non-users , the risk of hip fracture among women who regularly used PPIs for at least two years was 35 % higher ( age adjusted hazard ratio 1.35 ( 95 % confidence interval 1.13 to 1.62 ) ) , with longer use associated with increasing risk ( Ptrend fracture differed by smoking history ( Pinteraction=0.03 ) . Among current and former smokers , PPI use was associated with greater than 50 % increase in risk of fracture , with a multivariate hazard ratio for fracture of 1.51 ( 1.20 to 1.91 ) . In contrast , among women who never smoked there was no association ( multivariate hazard ratio 1.06 ( 0.77 to 1.46 ) ) . In a meta- analysis of these results with 10 prior studies , the pooled odds ratio of hip fracture associated with PPI use was 1.30 ( 1.25 to 1.36 ) . Conclusion Chronic use of PPIs is associated with increased risk of hip fracture , particularly among women with a history of smoking", "Summary A large Canadian cohort was studied over 10 years to see if proton pump inhibitor ( PPI ) use increased the risk of sustaining a fragility fracture . We found an increased risk of fracture in individuals who used PPIs . The risk remained after controlling for other known fracture risk factors . Introduction Multiple retrospective studies have linked proton pump inhibitor use with increased risk of fragility fracture . We prospect ively studied the association between PPI use and fracture in a large cohort over a 10-year period while controlling for known fracture risk factors . Methods We studied 9,423 participants in the Canadian Multicenter Osteoporosis Study . The cohort was formed in 1995–1997 and followed for 10 years with monitoring for incident nontraumatic fracture and PPI use . Cox regression analyses were used to assess the association between PPI use and incident fracture risk . Results PPI use , coded as a time-dependent variable , was associated with a shorter time to first nontraumatic fracture , hazard ratio ( HR ) = 1.75 ( 95 % confidence interval ( CI ) 1.41–2.17 , p femoral neck bone density , the association remained significant , HR = 1.40 ( 95 % CI 1.11–1.77 , p = 0.004 ) . Similar results were obtained after controlling for bisphosphonate use , using PPI “ ever ” use , or when the outcome was restricted to hip fracture . Conclusions In this large prospect i ve population -based cohort study , we found an association between PPI use and increased risk of fragility fracture . Although the increased risk found was modest , this finding is important , given the high prevalence of PPI use and the excess morbidity and mortality associated with osteoporosis-related fractures", "OBJECTIVES To determine the prevalence and economic effect of inappropriate proton pump inhibitor ( PPI ) use in an ambulatory care setting . STUDY DESIGN Retrospective medical record review of r and om sample with subgroup analysis . METHODS Patients were categorized according to appropriateness of pharmacotherapy based on documented upper gastrointestinal tract diagnoses , gastrointestinal or extraesophageal symptoms , or gastroprotection . Adverse events potentially associated with PPI use were identified . RESULTS Of 946 patients in an ambulatory care setting , 35.4 % were given PPI therapy for an appropriately documented upper gastrointestinal tract diagnosis , 10.1 % received PPIs empirically for symptomatic treatment based on extraesophageal symptoms , 18.4 % received PPIs for gastroprotection , and 36.1 % had no documented appropriate indication for PPI therapy . In a subgroup analysis , 48.6 % of patients across all 4 categories received PPIs without documentation of reevaluation of upper gastrointestinal tract symptoms , accounting for 1034 patient-years of PPI use . The total cost of inappropriate PPI use was $ 233,994 based on over-the-counter PPI costs and $ 1,566,252 based on average wholesale price costs . Potentially related adverse events in this cohort included Clostridium difficile – associated diarrhea ( 6 cases ) and community-acquired pneumonia ( 1 case ) , but no cases of hip fracture or vitamin B12 deficiency were identified . CONCLUSIONS Proton pump inhibitors are often overused in the ambulatory care setting without documented valid indications . Inappropriate use of PPIs is associated with substantial cost expenditure and with the potential for adverse events", "BACKGROUND Proton pump inhibitor ( PPI ) medications have been inconsistently shown to be associated with osteoporotic fractures . We examined the association of PPI use with bone outcomes ( fracture , bone mineral density [ BMD ] ) . METHODS This prospect i ve analysis included 161 806 postmenopausal women 50 to 79 years old , without history of hip fracture , enrolled in the Women 's Health Initiative ( WHI ) Observational Study and Clinical Trials with a mean ( SD ) follow-up of 7.8 ( 1.6 ) years . Analyses were conducted for 130 487 women with complete information . Medication information was taken directly from drug containers during in-person interviews ( baseline , year 3 ) . The main outcome measures were self-reported fractures ( hip [ adjudicated ] , clinical spine , forearm or wrist , and total fractures ) and for a sub sample ( 3 densitometry sites ) , 3-year change in BMD . RESULTS During 1 005 126 person-years of follow-up , 1500 hip fractures , 4881 forearm or wrist fractures , 2315 clinical spine fractures , and 21 247 total fractures occurred . The multivariate-adjusted hazard ratios for current PPI use were 1.00 ( 95 % confidence interval [ CI ] , 0.71 - 1.40 ) for hip fracture , 1.47 ( 95 % CI , 1.18 - 1.82 ) for clinical spine fracture , 1.26 ( 95 % CI , 1.05 - 1.51 ) for forearm or wrist fracture , and 1.25 ( 95 % CI , 1.15 - 1.36 ) for total fractures . The BMD measurements did not vary between PPI users and nonusers at baseline . Use of PPIs was associated with only a marginal effect on 3-year BMD change at the hip ( P = .05 ) but not at other sites . CONCLUSION Use of PPIs was not associated with hip fractures but was modestly associated with clinical spine , forearm or wrist , and total fractures", "Summary A frailty concept that includes psychological and cognitive markers was prospect ively shown to be associated with increased risk of multiple falls and fractures among 1,509 community dwelling older adults , especially in those aged 75 and over . The predictive ability of frailty is not superior to falls history . Introduction The concept of frailty has been defined with or without psychological and cognitive markers . Falls are associated with multiple risk factors , including cognitive and mood disorders . The purpose of this study was to investigate the association of a comprehensive concept of frailty and its components with falls and fractures in community-dwelling older adults and to compare its predictive ability with having a history of falls . Methods One thous and five hundred nine participants in the Longitudinal Aging Study Amsterdam aged ≥65 were assessed to determine fall history and the prevalence of nine frailty markers , including cognitive and psychological factors . The number of falls and time to second fall were prospect ively registered for 1 year . Fractures were registered for 6 years . Results Frailty was significantly associated with time to second fall : hazard ratio of 1.53 [ 95 % confidence interval ( CI ) , 1.07–2.18 ] and area under the receiver operating characteristic curve ( AUC ) of 0.58 ( CI , 0.53–0.62 ) . In participants aged ≥75 , frailty was associated with ≥2 falls : odds ratio ( OR ) of 1.74 ( CI , 1.19–2.55 ) and AUC of 0.62 ( CI , 0.55–0.68 ) . Frailty , adjusted for age and sex , was significantly associated with ≥2 fractures : OR of 3.67 ( CI , 1.47–9.15 ) . The AUCs for falls history ( aged ≥75 ) ranged from 0.62 ( CI , 0.58–0.67 ) for ≥1 falls to 0.67 ( CI , 0.59–0.74 ) for ≥3 falls . Conclusions A concept of frailty including psychological and cognitive markers is associated with both multiple falls and fractures . However , frailty is not superior to falls history for the selection of old persons at increased risk of recurrent falls", "OBJECTIVES To compare the validity of a parsimonious frailty index ( components : weight loss , inability to rise from a chair , and poor energy ( Study of Osteoporotic Fractures ( SOF ) index ) ) with that of the more complex Cardiovascular Health Study ( CHS ) index ( components : unintentional weight loss , low grip strength , poor energy , slowness , and low physical activity ) for prediction of adverse outcomes in older men . DESIGN Prospect i ve cohort study . SETTING Six U.S. centers . PARTICIPANTS Three thous and one hundred thirty-two men aged 67 and older . MEASUREMENTS Frailty status categorized as robust , intermediate stage , or frail using the SOF index and criteria similar to those used in CHS index . Falls were reported three times for 1 year . Disability ( > or=1 new impairments in performing instrumental activities of daily living ) ascertained at 1 year . Fractures and deaths ascertained during 3 years of follow-up . Analysis of area under the receiver operating characteristic curve ( AUC ) statistics compared for models containing the SOF index versus those containing the CHS index . RESULTS Greater evidence of frailty as defined by either index was associated with greater risk of adverse outcomes . Frail men had a higher age-adjusted risk of recurrent falls ( odds ratio (OR)=3.0 - 3.6 ) , disability ( OR=5.3 - 7.5 ) , nonspine fracture ( hazard ratio (HR)=2.2 - 2.3 ) , and death ( HR=2.5 - 3.5 ) ( P AUC comparisons revealed no differences between models with the SOF index and models with the CHS index in discriminating falls ( AUC=0.63 , P=.97 ) , disability ( AUC=0.68 , P=.86 ) , nonspine fracture ( AUC=0.63 , P=.90 ) , or death ( AUC=0.71 for model with SOF index and 0.72 for model with CHS index , P=.19 ) . CONCLUSION The simple SOF index predicts risk of falls , disability , fracture , and mortality in men as well as the more-complex CHS index", "Proton pump inhibitors ( PPIs ) are widely used in the elderly . Recent studies have suggested that long-term PPI therapy is associated with fractures in the elderly , however the mechanism remains unknown . We investigated the association between long-term PPI therapy ≥1 year and fracture risk factors including bone structure , falls , and balance-related function in a post hoc analysis of a longitudinal population -based prospect i ve cohort of elderly postmenopausal women and replicated the findings in a second prospect i ve study of falling in elderly postmenopausal women . Long-term PPI therapy was associated with increased risk of falls and fracture-related hospitalizations ; adjusted odds ratio ( AOR ) 2.17 ; 95 % CI , 1.25 - 3.77 ; p = 0.006 and 1.95 ; 95 % CI , 1.20 - 3.16 ; p = 0.007 , respectively . In the replication study , long-term PPI use was associated with an increased risk of self-reported falling ; AOR , 1.51 ; 95 % CI , 1.00 - 2.27 ; p = 0.049 . No association of long-term PPI therapy with bone structure was observed ; however , question naire-assessed falls-associated metrics such as limiting outdoor activity ( p = 0.002 ) and indoor activity ( p = 0.001 ) due to fear of falling , dizziness ( p and numbness of feet ( p = 0.017 ) and objective clinical measurement such as Timed Up and Go ( p = 0.002 ) and Romberg eyes closed ( p = 0.025 ) tests were all significantly impaired in long-term PPI users . Long-term PPI users were also more likely to have low vitamin B12 levels than non-users ( 50 % versus 21 % , p = 0.003 ) . In conclusion , similar to previous studies , we identified an increased fracture risk in subjects on long-term PPI therapy . This increase in fracture risk in elderly women , already at high risk of fracture , appears to be mediated via increased falls risk and falling rather than impaired bone structure and should be carefully considered when prescribing long-term PPI therapy" ]	41189e10-06ff-11f0-808a-c43d1ab1c353
Serotonergic hallucinogens produce alterations of perceptions , mood , and cognition , and have anxiolytic , antidepressant , and antiaddictive properties . These drugs act as agonists of frontocortical 5-HT2A receptors , but the neural basis of their effects are not well understood . Thus , we conducted a systematic review of neuroimaging studies analyzing the effects of serotonergic hallucinogens in man . Studies published in the PubMed , Lilacs , and SciELO data bases until 12 April 2016 were included using the following keywords : " ayahuasca " , " DMT " , " psilocybin " , " LSD " , " mescaline " crossed one by one with the terms " mri " , " fmri " , " pet " , " spect " , " imaging " and " neuroimaging " . Of 279 studies identified , 25 were included . Acute effects included excitation of frontolateral/frontomedial cortex , medial temporal lobe , and occipital cortex , and inhibition of the default mode network . Long-term use was associated with thinning of the posterior cingulate cortex , thickening of the anterior cingulate cortex , and decreased neocortical 5-HT2A receptor binding . Despite the high method ological heterogeneity and the small sample sizes , the results suggest that hallucinogens increase introspection and positive mood by modulating brain activity in the fronto-temporo-parieto-occipital cortex	[ "The modulating effects of serotonin on dopamine neurotransmission are not well understood , particularly in acute psychotic states . Positron emission tomography was used to examine the effect of psilocybin on the in vivo binding of [11C]raclopride to D2-dopamine receptors in the striatum in healthy volunteers after placebo and a psychotomimetic dose of psilocybin ( n = 7 ) . Psilocybin is a potent indoleamine hallucinogen and a mixed 5-HT2A and 5-HT1A receptor agonist . Psilocybin administration ( 0.25 mg/kg p.o . ) produced changes in mood , disturbances in thinking , illusions , elementary and complex visual hallucinations and impaired ego-functioning . Psilocybin significantly decreased [11C]raclopride receptor binding potential ( BP ) bilaterally in the cau date nucleus ( 19 % ) and putamen ( 20 % ) consistent with an increase in endogenous dopamine . Changes in [11C]raclopride BP in the ventral striatum correlated with depersonalization associated with euphoria . Together with previous reports of 5-HT receptor involvement in striatal dopamine release , it is concluded that stimulation of both 5-HT2A and 5-HT1A receptors may be important for the modulation of striatal dopamine release in acute psychoses . The present results indirectly support the hypothesis of a serotonin-dopamine dysbalance in schizophrenia and suggest that psilocybin is a valuable tool in the analysis of serotonin-dopamine interactions in acute psychotic states", "A recent large population study of 130,000 adults in the United States failed to find evidence for a link between psychedelic use ( lysergic acid diethylamide , psilocybin or mescaline ) and mental health problems . Using a new data set consisting of 135,095 r and omly selected United States adults , including 19,299 psychedelic users , we examine the associations between psychedelic use and mental health . After adjusting for sociodemographics , other drug use and childhood depression , we found no significant associations between lifetime use of psychedelics and increased likelihood of past year serious psychological distress , mental health treatment , suicidal thoughts , suicidal plans and suicide attempt , depression and anxiety . We failed to find evidence that psychedelic use is an independent risk factor for mental health problems . Psychedelics are not known to harm the brain or other body organs or to cause addiction or compulsive use ; serious adverse events involving psychedelics are extremely rare . Overall , it is difficult to see how prohibition of psychedelics can be justified as a public health measure", "Abstract A double-blind , r and omized , active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated with life-threatening diseases . Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart . The participants received either 200 & mgr;g of LSD ( n = 8) or 20 & mgr;g of LSD with an open-label crossover to 200 & mgr;g of LSD after the initial blinded treatment was unmasked ( n = 4 ) . At the 2-month follow-up , positive trends were found via the State-Trait Anxiety Inventory ( STAI ) in reductions in trait anxiety ( p = 0.033 ) with an effect size of 1.1 , and state anxiety was significantly reduced ( p = 0.021 ) with an effect size of 1.2 , with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events . STAI reductions were sustained for 12 months . These results indicate that when administered safely in a method ologically rigorous medically supervised psychotherapeutic setting , LSD can reduce anxiety , suggesting that larger controlled studies are warranted", "Ayahuasca , a South American psychotropic plant tea obtained from Banisteriopsis caapi and Psychotria viridis , combines monoamine oxidase-inhibiting β-carboline alkaloids with N , N-dimethyltryptamine ( DMT ) , a psychedelic agent showing 5-HT2A agonist activity . In a clinical research setting , ayahuasca has demonstrated a combined stimulatory and psychedelic effect profile , as measured by subjective effect self- assessment instruments and dose-dependent changes in spontaneous brain electrical activity , which parallel the time course of subjective effects . In the present study , the spatial distribution of ayahuasca-induced changes in brain electrical activity was investigated by means of low-resolution electromagnetic tomography ( LORETA ) . Electroencephalography recordings were obtained from 18 volunteers after the administration of a dose of encapsulated freeze-dried ayahuasca containing 0.85 mg DMT/kg body weight and placebo . The intracerebral power density distribution was computed with LORETA from spectrally analyzed data , and subjective effects were measured by means of the Hallucinogen Rating Scale ( HRS ) . Statistically significant differences compared to placebo were observed for LORETA power 60 and 90 min after dosing , together with increases in all six scales of the HRS . Ayahuasca decreased power density in the alpha-2 , delta , theta and beta-1 frequency b and s. Power decreases in the delta , alpha-2 and beta-1 b and s were found predominantly over the temporo-parieto-occipital junction , whereas theta power was reduced in the temporomedial cortex and in frontomedial regions . The present results suggest the involvement of unimodal and heteromodal association cortex and limbic structures in the psychological effects elicited by ayahuasca ", "Psilocybin-occasioned mystical experiences have been linked to persisting effects in healthy volunteers including positive changes in behavior , attitudes , and values , and increases in the personality domain of openness . In an open-label pilot- study of psilocybin-facilitated smoking addiction treatment , 15 smokers received 2 or 3 doses of psilocybin in the context of cognitive behavioral therapy ( CBT ) for smoking cessation . Twelve of 15 participants ( 80 % ) demonstrated biologically verified smoking abstinence at 6-month follow-up . Participants who were abstinent at 6 months ( n=12 ) were compared to participants still smoking at 6 months ( n=3 ) on measures of subjective effects of psilocybin . Abstainers scored significantly higher on a measure of psilocybin-occasioned mystical experience . No significant differences in general intensity of drug effects were found between groups , suggesting that mystical-type subjective effects , rather than overall intensity of drug effects , were responsible for smoking cessation . Nine of 15 participants ( 60 % ) met criteria for \" complete \" mystical experience . Smoking cessation outcomes were significantly correlated with measures of mystical experience on session days , as well as retrospective ratings of personal meaning and spiritual significance of psilocybin sessions . These results suggest a mediating role of mystical experience in psychedelic-facilitated addiction treatment", "Psychedelic drugs have a long history of use in healing ceremonies , but despite renewed interest in their therapeutic potential , we continue to know very little about how they work in the brain . Here we used psilocybin , a classic psychedelic found in magic mushrooms , and a task-free functional MRI ( fMRI ) protocol design ed to capture the transition from normal waking consciousness to the psychedelic state . Arterial spin labeling perfusion and blood-oxygen level-dependent ( BOLD ) fMRI were used to map cerebral blood flow and changes in venous oxygenation before and after intravenous infusions of placebo and psilocybin . Fifteen healthy volunteers were scanned with arterial spin labeling and a separate 15 with BOLD . As predicted , profound changes in consciousness were observed after psilocybin , but surprisingly , only decreases in cerebral blood flow and BOLD signal were seen , and these were maximal in hub regions , such as the thalamus and anterior and posterior cingulate cortex ( ACC and PCC ) . Decreased activity in the ACC/medial prefrontal cortex ( mPFC ) was a consistent finding and the magnitude of this decrease predicted the intensity of the subjective effects . Based on these results , a seed-based pharmaco-physiological interaction/functional connectivity analysis was performed using a medial prefrontal seed . Psilocybin caused a significant decrease in the positive coupling between the mPFC and PCC . These results strongly imply that the subjective effects of psychedelic drugs are caused by decreased activity and connectivity in the brain 's key connector hubs , enabling a state of unconstrained cognition", "Several lines of evidence suggest that classic ( 5HT2A agonist ) hallucinogens have clinical ly relevant effects in alcohol and drug addiction . Although recent studies have investigated the effects of psilocybin in various population s , there have been no studies on the efficacy of psilocybin for alcohol dependence . We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data . Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions . Participants ’ responses to psilocybin were qualitatively similar to those described in other population s. Abstinence did not increase significantly in the first 4 weeks of treatment ( when participants had not yet received psilocybin ) , but increased significantly following psilocybin administration ( p intensity of effects in the first psilocybin session ( at week 4 ) strongly predicted change in drinking during weeks 5–8 ( r = 0.76 to r = 0.89 ) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5 . There were no significant treatment-related adverse events . These preliminary findings provide a strong rationale for controlled trials with larger sample s to investigate efficacy and mechanisms . TRIAL REGISTRATION :", "Rationale Although psilocybin has been used for centuries for religious purpose s , little is known scientifically about its acute and persisting effects . Objectives This double-blind study evaluated the acute and longer-term psychological effects of a high dose of psilocybin relative to a comparison compound administered under comfortable , supportive conditions . Material s and methods The participants were hallucinogen-naïve adults reporting regular participation in religious or spiritual activities . Two or three sessions were conducted at 2-month intervals . Thirty volunteers received orally administered psilocybin ( 30 mg/70 kg ) and methylpheni date hydrochloride ( 40 mg/70 kg ) in counterbalanced order . To obscure the study design , six additional volunteers received methylpheni date in the first two sessions and unblinded psilocybin in a third session . The 8-h sessions were conducted individually . Volunteers were encouraged to close their eyes and direct their attention inward . Study monitors rated volunteers ’ behavior during sessions . Volunteers completed question naires assessing drug effects and mystical experience immediately after and 2 months after sessions . Community observers rated changes in the volunteer ’s attitudes and behavior . Results Psilocybin produced a range of acute perceptual changes , subjective experiences , and labile moods including anxiety . Psilocybin also increased measures of mystical experience . At 2 months , the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained positive changes in attitudes and behavior consistent with changes rated by community observers . Conclusions When administered under supportive conditions , psilocybin occasioned experiences similar to spontaneously occurring mystical experiences . The ability to occasion such experiences prospect ively will allow rigorous scientific investigations of their causes and consequences", "Rationale Attentional deficits are common symptoms in schizophrenia . Recent evidence suggests that schizophrenic patients show abnormalities in spatial orienting of attention , particularly a deficit of inhibition of return ( IOR ) . IOR is mostly thought to reflect an automatic , inhibitory mechanism protecting the organism from redirecting attention to previously scanned , insignificant locations . Pharmacologic challenges with hallucinogens have been used as models for psychosis . Objectives The aim of this study was to investigate the neural correlates underlying orienting of attention in the human N-methyl-d-aspartic acid antagonist and 5-HT2A agonist models of psychosis . Material s and methods Fourteen healthy volunteers participated in a r and omized , double-blind , cross-over event-related functional magnetic resonance imaging ( fMRI ) study with dimethyltryptamine ( DMT ) and S-ketamine . We administered a covert orienting of attention task with nonpredictive peripheral cues , and we scanned the subjects on two separate days at least 14 days apart with a placebo and a verum condition on each day . Results DMT , but not S-ketamine , slowed down reaction times significantly . IOR was blunted after DMT , but not after S-ketamine . Relative to placebo , S-ketamine increased activation in the IOR condition in the right superior frontal gyrus , left superior temporal gyrus , and right midfrontal frontal gyrus . Conclusions The discrepancy between the behavioral and functional imaging outcome indicates that pharmacological fMRI might be a sensitive tool to detect drug-modulated blood oxygenation level-dependent signal changes in the absence of behavioral abnormalities . Our findings might help to further clarify the contradictory findings of IOR in schizophrenic patients and might , thus , shed more light on possible differential pathomechanisms of schizophrenic symptoms", "Background The classical serotonergic psychedelics LSD , psilocybin , mescaline are not known to cause brain damage and are regarded as non-addictive . Clinical studies do not suggest that psychedelics cause long-term mental health problems . Psychedelics have been used in the Americas for thous and s of years . Over 30 million people currently living in the US have used LSD , psilocybin , or mescaline . Objective To evaluate the association between the lifetime use of psychedelics and current mental health in the adult population . Method Data drawn from years 2001 to 2004 of the National Survey on Drug Use and Health consisted of 130,152 respondents , r and omly selected to be representative of the adult population in the United States . St and ardized screening measures for past year mental health included serious psychological distress ( K6 scale ) , mental health treatment ( inpatient , outpatient , medication , needed but did not receive ) , symptoms of eight psychiatric disorders ( panic disorder , major depressive episode , mania , social phobia , general anxiety disorder , agoraphobia , posttraumatic stress disorder , and non-affective psychosis ) , and seven specific symptoms of non-affective psychosis . We calculated weighted odds ratios by multivariate logistic regression controlling for a range of sociodemographic variables , use of illicit drugs , risk taking behavior , and exposure to traumatic events . Results 21,967 respondents ( 13.4 % weighted ) reported lifetime psychedelic use . There were no significant associations between lifetime use of any psychedelics , lifetime use of specific psychedelics ( LSD , psilocybin , mescaline , peyote ) , or past year use of LSD and increased rate of any of the mental health outcomes . Rather , in several cases psychedelic use was associated with lower rate of mental health problems . Conclusion We did not find use of psychedelics to be an independent risk factor for mental health problems", "BACKGROUND The amygdala is a key structure in serotonergic emotion-processing circuits . In healthy volunteers , acute administration of the serotonin 1A/2A/2C receptor agonist psilocybin reduces neural responses to negative stimuli and induces mood changes toward positive states . However , it is little-known whether psilocybin reduces amygdala reactivity to negative stimuli and whether any change in amygdala reactivity is related to mood change . METHODS This study assessed the effects of acute administration of the hallucinogen psilocybin ( .16 mg/kg ) versus placebo on amygdala reactivity to negative stimuli in 25 healthy volunteers using blood oxygen level-dependent functional magnetic resonance imaging . Mood changes were assessed using the Positive and Negative Affect Schedule and the state portion of the State-Trait Anxiety Inventory . A double-blind , r and omized , cross-over design was used with volunteers counterbalanced to receive psilocybin and placebo in two separate sessions at least 14 days apart . RESULTS Amygdala reactivity to negative and neutral stimuli was lower after psilocybin administration than after placebo administration . The psilocybin-induced attenuation of right amygdala reactivity in response to negative stimuli was related to the psilocybin-induced increase in positive mood state . CONCLUSIONS These results demonstrate that acute treatment with psilocybin decreased amygdala reactivity during emotion processing and that this was associated with an increase of positive mood in healthy volunteers . These findings may be relevant to the normalization of amygdala hyperactivity and negative mood states in patients with major depression", "Rationale Ayahuasca is a South American psychoactive plant tea which contains the serotonergic psychedelic N , N-dimethyltryptamine ( DMT ) and monoamine-oxidase inhibitors that render DMT orally active . Previous investigations with ayahuasca have highlighted a psychotropic effect profile characterized by enhanced introspective attention , with individuals reporting altered somatic perceptions and intense emotional modifications , frequently accompanied by visual imagery . Despite recent advances in the study of ayahuasca pharmacology , the neural correlates of acute ayahuasca intoxication remain largely unknown . Objectives To investigate the effects of ayahuasca administration on regional cerebral blood flow . Methods Fifteen male volunteers with prior experience in the use of psychedelics received a single oral dose of encapsulated freeze-dried ayahuasca equivalent to 1.0 mg DMT/kg body weight and a placebo in a r and omized double-blind clinical trial . Regional cerebral blood flow was measured 100–110 min after drug administration by means of single photon emission tomography ( SPECT ) . Results Ayahuasca administration led to significant activation of frontal and paralimbic brain regions . Increased blood perfusion was observed bilaterally in the anterior insula , with greater intensity in the right hemisphere , and in the anterior cingulate/frontomedial cortex of the right hemisphere , areas previously implicated in somatic awareness , subjective feeling states , and emotional arousal . Additional increases were observed in the left amygdala/parahippocampal gyrus , a structure also involved in emotional arousal . Conclusions The present results suggest that ayahuasca interacts with neural systems that are central to interoception and emotional processing and point to a modulatory role of serotonergic neurotransmission in these processes", "BACKGROUND Anecdotal reports suggest that psychedelic agents may relieve symptoms of obsessive-compulsive disorder ( OCD ) . This modified double-blind study investigated the safety , tolerability , and clinical effects of psilocybin , a potent 5-HT(1A ) and 5-HT(2A/2C ) agonist , in patients with OCD . METHOD Nine subjects with DSM-IV-defined OCD and no other current major psychiatric disorder participated in up to 4 single-dose exposures to psilocybin in doses ranging from sub-hallucinogenic to frankly hallucinogenic . Low ( 100 microg/kg ) , medium ( 200 microg/kg ) , and high ( 300 microg/kg ) doses were assigned in that order , and a very low dose ( 25 microg/kg ) was inserted r and omly and in double-blind fashion at any time after the first dose . Testing days were separated by at least 1 week . Each session was conducted over an 8-hour period in a controlled environment in an outpatient clinic ; subjects were then transferred to a psychiatric inpatient unit for overnight observation . The Yale-Brown Obsessive Compulsive Scale ( YBOCS ) and a visual analog scale measuring overall obsessive-compulsive symptom severity were administered at 0 , 4 , 8 , and 24 hours post-ingestion . The Hallucinogen Rating Scale was administered at 8 hours , and vital signs were recorded at 0 , 1 , 4 , 8 , and 24 hours after ingestion . The study was conducted from November 2001 to November 2004 . RESULTS Nine subjects were administered a total of 29 psilocybin doses . One subject experienced transient hypertension without relation to anxiety or somatic symptoms , but no other significant adverse effects were observed . Marked decreases in OCD symptoms of variable degrees were observed in all subjects during 1 or more of the testing sessions ( 23%-100 % decrease in YBOCS score ) . Repeated- measures analysis of variance for all YBOCS values revealed a significant main effect of time on Wilks lambda ( F = 9.86 , df = 3,3 ; p = .046 ) , but no significant effect of dose ( F = 2.25 , df = 3,3 ; p = .261 ) or interaction of time and dose ( F = 0.923 , df = 9,45 ; p = .515 ) . Improvement generally lasted past the 24-hour timepoint . CONCLUSIONS In a controlled clinical environment , psilocybin was safely used in subjects with OCD and was associated with acute reductions in core OCD symptoms in several subjects", "BACKGROUND Validation of animal models of hallucinogenic drugs ' subjective effects requires human data . Previous human studies used varied groups of subjects and assessment methods . Rating scales for hallucinogen effects emphasized psychodynamic principles or the drugs ' dysphoric properties . We describe the subjective effects of grade d doses of N , N-dimethyltryptamine ( DMT ) , an endogenous hallucinogen and drug of abuse , in a group of experienced hallucinogen users . We also present preliminary data from a new rating scale for these effects . METHODS Twelve highly motivated volunteers received two doses ( 0.04 and 0.4 mg/kg ) of intravenous ( IV ) dimethyltryptamine fumarate \" nonblind , \" before entering a double-blind , saline placebo-controlled , r and omized study using four doses of IV DMT . Subjects were carefully interviewed after resolution of drug effects , providing thorough and systematic descriptions of DMT 's effects . They also were administered a new instrument , the Hallucinogen Rating Scale ( HRS ) . The HRS was drafted from interviews obtained from an independent sample of 19 experienced DMT users , and modified during early stages of the study . RESULTS Psychological effects of IV DMT began almost immediately after administration , peaked at 90 to 120 seconds , and were almost completely resolved by 30 minutes . This time course paralleled DMT blood levels previously described . Hallucinogenic effects were seen after 0.2 and 0.4 mg/kg of dimethyltryptamine fumarate , and included a rapidly moving , brightly colored visual display of images . Auditory effects were less common . \" Loss of control , \" associated with a brief , but overwhelming \" rush , \" led to a dissociated state , where euphoria alternated or coexisted with anxiety . These effects completely replaced subjects ' previously ongoing mental experience and were more vivid and compelling than dreams or waking awareness . Lower doses , 0.1 and 0.05 mg/kg , were primarily affective and somaesthetic , while 0.1 mg/kg elicited the least desirable effects . Clustering of HRS items , using either a clinical , mental status method or principal components factor analysis provided better resolution of dose effects than did the biological variables described previously . CONCLUSIONS These clinical and preliminary quantitative data provide bases for further psychopharmacologic characterization of DMT 's properties in humans . They also may be used to compare the effects of other agents affecting relevant brain receptors in volunteer and psychiatric population", "The hallucinogenic brew Ayahuasca , a rich source of serotonergic agonists and reuptake inhibitors , has been used for ages by Amazonian population s during religious ceremonies . Among all perceptual changes induced by Ayahuasca , the most remarkable are vivid \" seeings . \" During such seeings , users report potent imagery . Using functional magnetic resonance imaging during a closed-eyes imagery task , we found that Ayahuasca produces a robust increase in the activation of several occipital , temporal , and frontal areas . In the primary visual area , the effect was comparable in magnitude to the activation levels of natural image with the eyes open . Importantly , this effect was specifically correlated with the occurrence of individual perceptual changes measured by psychiatric scales . The activity of cortical areas BA30 and BA37 , known to be involved with episodic memory and the processing of context ual associations , was also potentiated by Ayahuasca intake during imagery . Finally , we detected a positive modulation by Ayahuasca of BA 10 , a frontal area involved with intentional prospect i ve imagination , working memory and the processing of information from internal sources . Therefore , our results indicate that Ayahuasca seeings stem from the activation of an extensive network generally involved with vision , memory , and intention . By boosting the intensity of recalled images to the same level of natural image , Ayahuasca lends a status of reality to inner experiences . It is therefore underst and able why Ayahuasca was culturally selected over many centuries by rain forest shamans to facilitate mystical revelations of visual nature", "Deficits in attentional functions belong to the core cognitive symptoms in schizophrenic patients . Alertness is a nonselective attention component that refers to a state of general readiness that improves stimulus processing and response initiation . The main goal of the present study was to investigate cerebral correlates of alertness in the human 5HT2A agonist and N-methyl-D-aspartic acid ( NMDA ) antagonist model of psychosis . Fourteen healthy volunteers participated in a r and omized double-blind , cross-over event-related functional magnetic resonance imaging ( fMRI ) study with dimethyltryptamine ( DMT ) and S-ketamine . A target detection task with cued and uncued trials in both the visual and the auditory modality was used . Administration of DMT led to decreased blood oxygenation level-dependent response during performance of an alertness task , particularly in extrastriate regions during visual alerting and in temporal regions during auditory alerting . In general , the effects for the visual modality were more pronounced . In contrast , administration of S-ketamine led to increased cortical activation in the left insula and pre central gyrus in the auditory modality . The results of the present study might deliver more insight into potential differences and overlapping pathomechanisms in schizophrenia . These conclusions must remain preliminary and should be explored by further fMRI studies with schizophrenic patients performing modality-specific alertness tasks", "AIMS Ayahuasca is a traditional South American psychoactive beverage used in Amazonian shamanism , and in the religious ceremonies of Brazilian-based syncretic religious groups with followers in the US and several European countries . This tea contains measurable amounts of the psychotropic indole N , N-dimethyltryptamine ( DMT ) , and beta-carboline alkaloids with MAO-inhibiting properties . In a previous report we described a profile of stimulant and psychedelic effects for ayahuasca as measured by subjective report self- assessment instruments . In the present study the cerebral bioavailability and time-course of effects of ayahuasca were assessed in humans by means of topographic quantitative-electroencephalography ( q-EEG ) , a noninvasive method measuring drug-induced variations in brain electrical activity . METHODS Two doses ( one low and one high ) of encapsulated freeze-dried ayahuasca , equivalent to 0.6 and 0.85 mg DMT kg(-1 ) body weight , were administered to 18 healthy volunteers with previous experience in psychedelic drug use in a double-blind crossover placebo-controlled clinical trial . Nineteen-lead recordings were undertaken from baseline to 8 h after administration . Subjective effects were measured by means of the Hallucinogen Rating Scale ( HRS ) . RESULTS Ayahuasca induced a pattern of psychoactive effects which result ed in significant dose-dependent increases in all subscales of the HRS , and in significant and dose-dependent modifications of brain electrical activity . Absolute power decreased in all frequency b and s , most prominently in the theta b and . Mean absolute power decreases ( 95 % CI ) at a representative lead ( P3 ) 90 min after the high dose were -20.20+/-15.23 microV2 and -2.70+/-2.21 microV2 for total power and theta power , respectively . Relative power decreased in the delta ( -1.20+/-1.31 % after 120 min at P3 ) and theta ( -3.30+/-2.59 % after 120 min at P3 ) b and s , and increased in the beta b and , most prominently in the faster beta-3 ( 1.00+/-0.88 % after 90 min at P3 ) and beta-4 ( 0.30+/-0.24 % after 90 min at P3 ) subb and s. Finally , an increase was also seen for the centroid of the total activity and its deviation . EEG modifications began as early as 15 - 30 min , reached a peak between 45 and 120 min and decreased thereafter to return to baseline levels at 4 - 6 h after administration . CONCLUSIONS The central effects of ayahuasca could be objective ly measured by means of q-EEG , showing a time pattern which closely paralleled that of previously reported subjective effects . The modifications seen for the individual q-EEG variables were in line with those previously described for other serotonergic psychedelics and share some features with the profile of effects shown by pro-serotonergic and pro-dopaminergic drugs . The q-EEG profile supports the role of 5-HT2 and dopamine D2-receptor agonism in mediating the effects of ayahuasca on the central nervous system", "Despite suggestive early findings on the therapeutic use of hallucinogens in the treatment of substance use disorders , rigorous follow-up has not been conducted . To determine the safety and feasibility of psilocybin as an adjunct to tobacco smoking cessation treatment we conducted an open-label pilot study administering moderate ( 20 mg/70 kg ) and high ( 30 mg/70 kg ) doses of psilocybin within a structured 15-week smoking cessation treatment protocol . Participants were 15 psychiatrically healthy nicotine-dependent smokers ( 10 males ; mean age of 51 years ) , with a mean of six previous lifetime quit attempts , and smoking a mean of 19 cigarettes per day for a mean of 31 years at intake . Biomarkers assessing smoking status , and self-report measures of smoking behavior demonstrated that 12 of 15 participants ( 80 % ) showed seven-day point prevalence abstinence at 6-month follow-up . The observed smoking cessation rate substantially exceeds rates commonly reported for other behavioral and /or pharmacological therapies ( typically psilocybin , these findings suggest psilocybin may be a potentially efficacious adjunct to current smoking cessation treatment models . The present study illustrates a framework for future research on the efficacy and mechanisms of hallucinogen-facilitated treatment of addiction", "BACKGROUND After no research in humans for > 40 years , there is renewed interest in using lysergic acid diethylamide ( LSD ) in clinical psychiatric research and practice . There are no modern studies on the subjective and autonomic effects of LSD , and its endocrine effects are unknown . In animals , LSD disrupts prepulse inhibition ( PPI ) of the acoustic startle response , and patients with schizophrenia exhibit similar impairments in PPI . However , no data are available on the effects of LSD on PPI in humans . METHODS In a double-blind , r and omized , placebo-controlled , crossover study , LSD ( 200 μg ) and placebo were administered to 16 healthy subjects ( 8 women , 8 men ) . Outcome measures included psychometric scales ; investigator ratings ; PPI of the acoustic startle response ; and autonomic , endocrine , and adverse effects . RESULTS Administration of LSD to healthy subjects produced pronounced alterations in waking consciousness that lasted 12 hours . The predominant effects induced by LSD included visual hallucinations , audiovisual synesthesia , and positively experienced derealization and depersonalization phenomena . Subjective well-being , happiness , closeness to others , openness , and trust were increased by LSD . Compared with placebo , LSD decreased PPI . LSD significantly increased blood pressure , heart rate , body temperature , pupil size , plasma cortisol , prolactin , oxytocin , and epinephrine . Adverse effects produced by LSD completely subsided within 72 hours . No severe acute adverse effects were observed . CONCLUSIONS In addition to marked hallucinogenic effects , LSD exerts methylenedioxymethamphetamine-like empathogenic mood effects that may be useful in psychotherapy . LSD altered sensorimotor gating in a human model of psychosis , supporting the use of LSD in translational psychiatric research . In a controlled clinical setting , LSD can be used safely , but it produces significant sympathomimetic stimulation", "Rationale This dose-effect study extends previous observations showing that psilocybin can occasion mystical-type experiences having persisting positive effects on attitudes , mood , and behavior . Objectives This double-blind study evaluated psilocybin ( 0 , 5 , 10 , 20 , 30 mg/70 kg , p.o . ) administered under supportive conditions . Methods Participants were 18 adults ( 17 hallucinogen-naïve ) . Five 8-h sessions were conducted individually for each participant at 1-month intervals . Participants were r and omized to receive the four active doses in either ascending or descending order ( nine participants each ) . Placebo was scheduled quasi-r and omly . During sessions , volunteers used eyeshades and were instructed to direct their attention inward . Volunteers completed question naires assessing effects immediately after and 1 month after each session , and at 14 months follow-up . Results Psilocybin produced acute perceptual and subjective effects including , at 20 and /or 30 mg/70 kg , extreme anxiety/fear ( 39 % of volunteers ) and /or mystical-type experience ( 72 % of volunteers ) . One month after sessions at the two highest doses , volunteers rated the psilocybin experience as having substantial personal and spiritual significance , and attributed to the experience sustained positive changes in attitudes , mood , and behavior , with the ascending dose sequence showing greater positive effects . At 14 months , ratings were undiminished and were consistent with changes rated by community observers . Both the acute and persisting effects of psilocybin were generally a monotonically increasing function of dose , with the lowest dose showing significant effects . Conclusions Under supportive conditions , 20 and 30 mg/70 kg psilocybin occasioned mystical-type experiences having persisting positive effects on attitudes , mood , and behavior . Implication s for therapeutic trials are discussed", "BACKGROUND Serotonin ( 5-HT ) 1A and 2A receptors have been associated with dysfunctional emotional processing biases in mood disorders . These receptors further predominantly mediate the subjective and behavioral effects of psilocybin and might be important for its recently suggested antidepressive effects . However , the effect of psilocybin on emotional processing biases and the specific contribution of 5-HT2A receptors across different emotional domains is unknown . METHODS In a r and omized , double-blind study , 17 healthy human subjects received on 4 separate days placebo , psilocybin ( 215 μg/kg ) , the preferential 5-HT2A antagonist ketanserin ( 50 mg ) , or psilocybin plus ketanserin . Mood states were assessed by self-report ratings , and behavioral and event-related potential measurements were used to quantify facial emotional recognition and goal -directed behavior toward emotional cues . RESULTS Psilocybin enhanced positive mood and attenuated recognition of negative facial expression . Furthermore , psilocybin increased goal -directed behavior toward positive compared with negative cues , facilitated positive but inhibited negative sequential emotional effects , and valence-dependently attenuated the P300 component . Ketanserin alone had no effects but blocked the psilocybin-induced mood enhancement and decreased recognition of negative facial expression . CONCLUSIONS This study shows that psilocybin shifts the emotional bias across various psychological domains and that activation of 5-HT2A receptors is central in mood regulation and emotional face recognition in healthy subjects . These findings may not only have implication s for the pathophysiology of dysfunctional emotional biases but may also provide a framework to delineate the mechanisms underlying psylocybin 's putative antidepressant effects", "Objective : A recently published study showed the safety and efficacy of LSD-assisted psychotherapy in patients with anxiety associated with life-threatening diseases . Participants of this study were included in a prospect i ve follow-up . Method : 12 months after finishing LSD psychotherapy , 10 participants were tested for anxiety ( STAI ) and participated in a semi-structured interview . A Qualitative Content Analysis ( QCA ) was carried out on the interviews to elaborate about LSD effects and lasting psychological changes . Results : None of the participants reported lasting adverse reactions . The significant benefits as measured with the STAI were sustained over a 12-month period . In the QCA participants consistently reported insightful , cathartic and interpersonal experiences , accompanied by a reduction in anxiety ( 77.8 % ) and a rise in quality of life ( 66.7 % ) . Evaluations of subjective experiences suggest facilitated access to emotions , confrontation of previously unknown anxieties , worries , re sources and intense emotional peak experiences à la Maslow as major psychological working mechanisms . The experiences created led to a restructuring of the person ’s emotional trust , situational underst and ing , habits and world view . Conclusions : LSD administered in a medically supervised psychotherapeutic setting can be safe and generate lasting benefits in patients with a life-threatening disease . Explanatory models for the therapeutic effects of LSD warrant further study", "Ayahuasca is an Amazonian psychotropic plant tea typically obtained from two plants , Banisteriopsis caapi and Psychotria viridis . It contains the psychedelic 5-HT2A and sigma-1 agonist N , N-dimethyltryptamine ( DMT ) plus β-carboline alkaloids with monoamine-oxidase (MAO)-inhibiting properties . Although the psychoactive effects of ayahuasca have commonly been attributed solely to agonism at the 5-HT2A receptor , the molecular target of classical psychedelics , this has not been tested experimentally . Here we wished to study the contribution of the 5-HT2A receptor to the neurophysiological and psychological effects of ayahuasca in humans . We measured drug-induced changes in spontaneous brain oscillations and subjective effects in a double-blind r and omized placebo-controlled study involving the oral administration of ayahuasca ( 0.75 mg DMT/kg body weight ) and the 5-HT2A antagonist ketanserin ( 40 mg ) . Twelve healthy , experienced psychedelic users ( 5 females ) participated in four experimental sessions in which they received the following drug combinations : placebo+placebo , placebo+ayahuasca , ketanserin+placebo and ketanserin+ayahuasca . Ayahuasca induced EEG power decreases in the delta , theta and alpha frequency b and s. Current density in alpha-b and oscillations in parietal and occipital cortex was inversely correlated with the intensity of visual imagery induced by ayahuasca . Pretreatment with ketanserin inhibited neurophysiological modifications , reduced the correlation between alpha and visual effects , and attenuated the intensity of the subjective experience . These findings suggest that despite the chemical complexity of ayahuasca , 5-HT2A activation plays a key role in the neurophysiological and visual effects of ayahuasca in humans", "PSILOCYBIN , an indoleamine hallucinogen , produces a psychosis-like syndrome in humans that resembles first episodes of schizophrenia . In healthy human volunteers , the psychotomimetic effects of psilocybin were blocked dose-dependently by the serotonin-2A antagonist ketanserin or the atypical antipsychotic risperidone , but were increased by the dopamine antagonist and typical antipsychotic haloperidol . These data are consistent with animal studies and provide the first evidence in humans that psilocybin-induced psychosis is due to serotonin-2A receptor activation , independently of dopamine stimulation . Thus , serotonin-2A overactivity may be involved in the pathophysiology of schizophrenia and serotonin-2A antagonism may contribute to therapeutic effects of antipsychotics", "Abstract Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine , a 5-HT2A receptor agonist , and harmine , a monoamine-oxidase A inhibitor . Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients . The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow . In an open-label trial conducted in an inpatient psychiatric unit , 17 patients with recurrent depression received an oral dose of ayahuasca ( 2.2 mL/kg ) and were evaluated with the Hamilton Rating Scale for Depression , the Montgomery-Åsberg Depression Rating Scale , the Brief Psychiatric Rating Scale , the Young Mania Rating Scale , and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1 , 7 , 14 , and 21 days after drug intake . Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography . Ayahuasca administration was associated with increased psychoactivity ( Clinician Administered Dissociative States Scale ) and significant score decreases in depression-related scales ( Hamilton Rating Scale for Depression , Montgomery-Åsberg Depression Rating Scale , Brief Psychiatric Rating Scale ) from 80 minutes to day 21 . Increased blood perfusion in the left nucleus accumbens , right insula and left subgenual area , brain regions implicated in the regulation of mood and emotions , were observed after ayahuasca intake . Ayahuasca was well tolerated . Vomiting was the only adverse effect recorded , being reported by 47 % of the volunteers . Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties . These results should be replicated in r and omized , double-blind , placebo-controlled trials" ]	41189e4c-06ff-11f0-808a-c43d1ab1c353
Background : It is now well-established that sedentarity has a negative impact on the physiological functioning and health of humans , whereas very little is known about the psychological repercussions , especially in cognitive functioning . Yet , study ing the cognitive effects of the sedentary lifestyle is particularly relevant in the short term for productivity and in the long term for cognitive health ( accelerated aging ) . This systematic review therefore aims to make an inventory of the potential cognitive effects of sedentarity at the workplace . Methods : Pubmed , PsycINFO , Cochrane , Web of Science , and Scopus were search ed for English- language peer- review ed articles published between January 1 , 2000 and December 31 , 2017 to identify studies including sedentary behavior and objective measures from cognitive domains ( cognitive inhibition , cognitive flexibility , working memory , etc . ) . To carry out this systematic review , the 3 keywords " Sedentary " and " Cognition " and " Work " ( and their derivatives ) had to appear in the title or in the summary of the paper . Results : Of the 13 papers that met the inclusion criteria , 9 were short-term interventions , 3 medium-term interventions , and 1 long-term intervention . Nine of them reported non-significant results . Two studies study reported deterioration in cognitive performance . Two reported an improvement in performance in cognitive tasks with one study with overweight adults and the only one study with a long-term intervention . However , these studies intend to reduce sedentary behavior , but do not allow answering the question of the potential cognitive effects of the sedentary lifestyle . Conclusion : These data suggest that sedentary behavior is not associated with changes in cognitive performance in interventions that intend to reduce sedentary behavior . Then , and given the trend toward increased time in sedentary behavior , long-term prospect i ve studies of high method ological quality are recommended to clarify the relationships between sedentary behavior and the cognitive functioning . Our systematic review identifies also the need for retrospective , longitudinal , or epidemiologic studies . It also recognizes the need to st and ardize methodology for collecting , defining , and reporting sedentary behavior and the need to st and ardize the cognitive tests used . The relationship between sedentary behavior and cognitive functioning remaining uncertain , further studies are warranted for which 8 recommendations are proposed	[ "In the current work we asked whether executive function , as measured by tests of working memory capacity , might benefit from an acute bout of exercise and , more specifically , whether individuals who are lower or higher in working memory to begin with would be more or less affected by an exercise manipulation . Healthy adults completed working memory measures in a nonexercise ( baseline ) session and immediately following a 30-min self-paced bout of exercise on a treadmill ( exercise session ) . Sessions were conducted 1 week apart and session order was counterbalanced across participants . A significant Session x Working Memory interaction was obtained such that only those individuals lowest in working memory benefited from the exercise manipulation . This work suggests that acute bouts of exercise may be most beneficial for healthy adults whose cognitive performance is generally the lowest , and it demonstrates that the impact of exercise on cognition is not uniform across all individuals", "Background Although basic research has uncovered biological mechanisms by which exercise could maintain and enhance adult brain health , experimental human studies with older adults have produced equivocal results . Purpose This r and omized clinical trial aim ed to investigate the hypotheses that ( a ) the effects of exercise training on the performance of neurocognitive tasks in older adults is selective , influencing mainly tasks with a substantial executive control component and ( b ) performance in neurocognitive tasks is related to cardiorespiratory fitness . Methods Fifty-seven older adults ( 65–79 years ) participated in aerobic or strength- and -flexibility exercise training for 10 months . Neurocognitive tasks were selected to reflect a range from little ( e.g. , simple reaction time ) to substantial ( i.e. , Stroop Word – Color conflict ) executive control . Results Performance in tasks requiring little executive control was unaffected by participating in aerobic exercise . Improvements in Stroop Word – Color task performance were found only for the aerobic exercise group . Changes in aerobic fitness were unrelated to changes in neurocognitive function . Conclusions Aerobic exercise in older adults can have a beneficial effect on the performance of speeded tasks that rely heavily on executive control . Improvements in aerobic fitness do not appear to be a prerequisite for this beneficial effect", "We investigated the cross-sectional and prospect i ve associations between different sedentary behaviors and cognitive function in a large sample of adults with data stored in the UK Biobank . Baseline data were available for 502,643 participants ( 2006 - 2010 , United Kingdom ) . Cognitive tests included prospect i ve memory ( baseline only : n = 171,585 ) , visual-spatial memory ( round 1 : n = 483,832 ; round 2 : n = 482,762 ) , fluid intelligence ( n = 165,492 ) , and short-term numeric memory ( n = 50,370 ) . After a mean period of 5.3 years , participants ( numbering from 12,091 to 114,373 , depending on the test ) also provided follow-up cognitive data . Sedentary behaviors ( television viewing , driving , and nonoccupational computer-use time ) were measured at baseline . At baseline , both television viewing and driving time were inversely associated with cognitive function across all outcomes ( e.g. , for each additional hour spent watching television , the total number of correct answers in the fluid intelligence test was 0.15 ( 99 % confidence interval : 0.14 , 0.16 ) lower . Computer-use time was positively associated with cognitive function across all outcomes . Both television viewing and driving time at baseline were positively associated with the odds of having cognitive decline at follow-up across most outcomes . Conversely , computer-use time at baseline was inversely associated with the odds of having cognitive decline at follow-up across most outcomes . This study supports health policies design ed to reduce television viewing and driving in adults", "Adults are sedentary for an alarming 9 to 10 hours per day ( 1 ) . Accordingly , the popular press has coined the phrase sitting is the new smoking to describe a current epidemic of developed nations ( 24 ) . Evidence indicates that sedentary time is associated with incident cardiovascular disease , incidence of cardiovascular diseaserelated risk factors , and mortality ( 5 , 6 ) . Of note , the risk conferred by prolonged sedentariness is eliminated only by high levels of moderate- to vigorous-intensity physical activity ( MVPA ) ( about 60 to 75 min/d ) , which exceed physical activity recommendations ( 7 , 8) . As such , sedentary behavior is now believed to represent a clinical ly important aspect of a person 's physical activity profile and is no longer considered simply the extreme low end of the physical activity continuum ( 5 ) . Studies linking sedentary behavior to health outcomes have relied almost exclusively on self-reported sedentary time , which is subject to reporting bias and measurement error ( 9 ) . A 2015 systematic review ( 5 ) identified only 1 study ( NHANES [ National Health and Nutrition Examination Survey ] ) that examined the association between objective ly measured sedentary time and health outcomes , a study limited by a small event rate ( 10 ) . New studies using NHANES data have since been published , with longer follow-up and higher event rates ( 1115 ) . However , some of these studies have reported an association between objective ly measured sedentary time and mortality ( 11 , 14 , 15 ) , but others have not ( 12 , 13 ) . Additional cohort studies are thus needed to rectify evidence gaps . Furthermore , studies using accelerometers to objective ly measure sedentary behavior conventionally operationalize sedentary time as the total number of sedentary minutes per day . This approach ignores patterns of accumulated sedentary behavior over time . For example , accumulation of sedentary time in a few long bouts or many short bouts represents 2 distinct patterns of sedentary time accrual . Experimental studies have shown that acute periods of prolonged , uninterrupted sedentary behavior cause greater detrimental cardiometabolic effects than sedentary behavior that is periodically interrupted ( 1618 ) , suggestive that it is not just total sedentary time that is relevant to health outcomes , but also the manner in which it is accumulated . Few longitudinal studies , however , have explored the association between prolonged , uninterrupted sedentary behavior and mortality to corroborate these findings . To inform guidelines on reducing sedentary behavior ( target reductions in overall sedentary time or target interruption of prolonged sedentary bouts ) , evidence from prospect i ve studies is needed to 1 ) confirm the association between total sedentary time and mortality using objective measures , 2 ) determine whether prolonged sedentary bouts confer risk for death , and 3 ) eluci date whether the total volume of sedentary time and its pattern of accumulation individually or jointly contribute to risk for death . The purpose of this study , therefore , was to examine the association between objective ly measured sedentary time ( both total volume and accrual in prolonged bouts ) and all-cause mortality in a national cohort of U.S. middle-aged and older adults enrolled in the REGARDS ( Reasons for Geographic and Racial Differences in Stroke ) study . Methods Study Population REGARDS is a population -based study design ed to examine racial and regional disparities in stroke . It comprises 30239 white and black adults aged 45 years or older enrolled between 2003 and 2007 from across the contiguous United States ( 19 , 20 ) . Detailed design and methods for REGARDS are described elsewhere ( 21 ) . Briefly , demographic and cardiovascular risk factor data were collected by telephone interview and an in-home physical assessment on enrollment . A detailed summary of baseline measures is provided in the Supplement . Participants ( or their proxies ) were then followed for 6-month intervals to ascertain vital status . Objective measurements of sedentary behavior were collected from active REGARDS participants from 2009 to 2013 ( mean time from study enrollment , 5.7 years [ SD , 1.5 ] ; range , 1.9 to 9.5 years ) ( 22 ) . A total of 7985 participants adhered to accelerometer wear requirements ( 4 days with accelerometer wear 10 hours ) , provided follow-up data , and were available for the current analyses ( Supplement Figure 1 ) . Supplement Table 1 shows the characteristics of included versus excluded REGARDS participants . The REGARDS study protocol was approved by the institutional review boards of participating institutions . All participants provided informed consent . Supplement . Supplementary Material Accelerometer Data Collection Methods for accelerometer data collection are described elsewhere ( 22 ) . Briefly , participants were fitted with an Actical ( Philips Respironics ) accelerometer secured to their right hip using a nylon belt and were instructed to wear the device during waking hours for 7 consecutive days . The Actical had been vali date d formeasurement of physical activity and sedentary behavior and was shown to have acceptable reliability ( 2325 ) . Activity counts were summed over 1-minute epochs . Nonwear periods were defined as at least 150 consecutive minutes of 0 activity counts . This nonwear algorithm was previously vali date d against daily log sheets in REGARDS participants ( 26 ) . Measurements of 0 to 49 , 50 to 1064 , and at least 1065 counts per minute were defined as sedentary behavior , light-intensity physical activity , and MVPA , respectively , as determined in a laboratory-based calibration study ( 27 ) . A sedentary bout was defined as consecutive minutes in which the accelerometer registered fewer than 50 counts per minute . A sedentary break was defined as at least 1 minute in which 50 or more counts per minute were registered after a sedentary bout . Both sedentary bouts and breaks were exclusively continuous periods , with no interruptions or nonwear intervals allowed in the definition . Outcome Ascertainment All-cause mortality was the primary outcome , defined as any death after completion of the accelerometer protocol regardless of cause . Date s of death were confirmed through review of death certificates , medical records , and administrative data bases . Deaths through 4 September 2015 were included in the current analysis . Statistical Analysis Sedentary and physical activity variables were averaged across compliant days ( 10 hours of wear ) . Because of a high correlation between total sedentary time and wear time ( Supplement Figure 2 ) , we corrected for the influence of wear time by st and ardizing total sedentary time to 16 hours of wear time per day using the residuals obtained when regressing total sedentary time on wear time ( see Methods section of the Supplement ) ( 2830 ) . Participants were stratified into quartiles according to total sedentary time and , separately , mean sedentary bout duration ( a measure of overall prolonged , uninterrupted sedentary behavior ) . Cox proportional hazards regression modeling was used to calculate the hazard ratio ( HR ) for all-cause mortality associated with quartiles of total sedentary time ( and separately , mean sedentary bout length ) . Crude HRs were initially calculated . Subsequent HRs were calculated after adjustment for age , race , sex , region of residence , education , and season the accelerometer was worn ( model 1 ) , with further adjustment for current smoking , alcohol use , body mass index ( BMI ) , diabetes , hypertension , dyslipidemia , estimated glomerular filtration rate less than 60 mL/min/1.73 m2 , atrial fibrillation , history of coronary heart disease , and history of stroke ( model 2 ) . Models were additionally adjusted for MVPA expressed continuously ( model 3 ) . Tests for linear trend across quartiles were conducted by including the quartile for each participant as an ordinal variable in regression models . Proportional hazards assumptions were confirmed with a Kolmogorov-type supremum test ( 31 ) . The above analyses were then repeated in a fully adjusted model , testing interactions for age ( , sex ( male and female ) , race ( black and white ) , BMI category ( normal weight and overweight or obese ) , and MVPA category ( . As a secondary analysis , we examined the continuous doseresponse relationship between each sedentary characteristic and all-cause mortality in a fully adjusted model ( model 3 ) using restricted cubic splines ( 32 ) . Cubic polynomials were fitted with the mean of each sedentary characteristic set as the reference and knots placed at the 5th , 35th , 65th , and 95th percentiles ( 33 ) . Nonlinear associations were evaluated using the likelihood ratio test . For nonlinear associations , spline models were used to describe the associations and when the association was determined to be linear , a linear model was used . Because of multicollinearity between total sedentary time and mean sedentary bout duration ( r= 0.61 ) , both variables were not included in the same model . Alternatively , to examine the individual and joint associations of total sedentary time and prolonged , uninterrupted sedentary behavior with mortality , participants were classified into 4 categories : low total sedentary time ( sedentary bout time ( low total sedentary time and high prolonged sedentary bout time ( 10 min/bout ) , high total sedentary time ( 750 min/d ) and low prolonged sedentary bout time , and high total sedentary time and high prolonged sedentary bout time . Hazard ratios for all-cause mortality were calculated for each joint category in comparison with the lowlow group in a fully adjusted model ( model 3 ) . Thresholds for total sedentary time ( 750 min/d ) and mean sedentary bout duration ( 10 min/bout ) were selected on the basis of the restricted cubic splines and were confirmed using a method described by Contal and O'Quigley ( see Methods section of the Supplement ) ( 34 ) . To allow for the possibility that sedentary bouts", "Abstract Recent attention has highlighted the importance of reducing sedentary time for maintaining health and quality of life . However , it is unclear how changing sedentary behavior may influence executive functions and self-regulatory strategy use , which are vital for the long-term maintenance of a health behavior regimen . The purpose of this cross-sectional study is to examine the estimated self-regulatory and executive functioning effects of substituting 30 min of sedentary behavior with 30 min of light activity , moderate-to-vigorous physical activity ( MVPA ) , or sleep in a sample of older adults . This study reports baseline data collected from low-active healthy older adults ( N = 247 , mean age 65.4 ± 4.6 years ) recruited to participate in a 6 month r and omized controlled exercise trial examining the effects of various modes of exercise on brain health and function . Each participant completed assessment s of physical activity self-regulatory strategy use ( i.e. , self-monitoring , goal - setting , social support , reinforcement , time management , and relapse prevention ) and executive functioning . Physical activity and sedentary behaviors were measured using accelerometers during waking hours for seven consecutive days at each time point . Isotemporal substitution analyses were conducted to examine the effect on self-regulation and executive functioning should an individual substitute sedentary time with light activity , MVPA , or sleep . The substitution of sedentary time with both sleep and MVPA influenced both self-regulatory strategy use and executive functioning . Sleep was associated with greater self-monitoring ( B = .23 , p = .02 ) , goal - setting ( B = .32 , p and social support ( B = .18 , p = .01 ) behaviors . Substitution of sedentary time with MVPA was associated with higher accuracy on 2-item ( B = .03 , p = .01 ) and 3-item ( B = .02 , p = .04 ) spatial working memory tasks , and with faster reaction times on single ( B = −23.12 , p = .03 ) and mixed-repeated task-switching blocks ( B = −27.06 , p = .04 ) . Substitution of sedentary time with sleep was associated with marginally faster reaction time on mixed-repeated task-switching blocks ( B = −12.20 , p = .07 ) and faster reaction time on mixed-switch blocks ( B = 17.21 , p = .05 ) , as well as reduced global reaction time switch cost ( B = −16.86 , p = .01 ) . Substitution for light intensity physical activity did not produce significant effects . By replacing sedentary time with sleep and MVPA , individuals may bolster several important domains of self-regulatory behavior and executive functioning . This has important implication s for the design of long-lasting health behavior interventions . Trial Registration clinical trials.gov identifier NCT00438347", "Abstract Prolonged sitting is a risk factor for several diseases and the prevalence of worksite-based interventions such as sit-to-st and workstations is increasing . Although their impact on sedentary behaviour has been regularly investigated , the effect of working in alternating body postures on cognitive performance is unclear . To address this uncertainty , 45 students participated in a two-arm , r and omised controlled cross-over trial under laboratory conditions . Subjects executed vali date d cognitive tests ( working speed , reaction time , concentration performance ) either in sitting or alternating working postures on two separate days ( Clinical Trials.gov Identifier : NCT02863731 ) . MANOVA results showed no significant difference in cognitive performance between trials executed in alternating , st and ing or sitting postures . Perceived workload did not differ between sitting and alternating days . Repeated measures ANOVA revealed significant learning effects regarding concentration performance and working speed for both days . These results suggest that working posture did not affect cognitive performance in the short term . Practitioner Summary : Prior reports indicated health-related benefits based on alternated ( sit/st and ) body postures . Nevertheless , their effect on cognitive performance is unknown . This r and omised controlled trial showed that working in alternating body postures did not influence reaction time , concentration performance , working speed or workload perception in the short term", "Background While physical activity has been shown to improve cognitive performance and well-being , office workers are essentially sedentary . We compared the effects of physical activity performed as ( i ) one bout in the morning or ( ii ) as microbouts spread out across the day to ( iii ) a day spent sitting , on mood and energy levels and cognitive function . Methods In a r and omized crossover trial , 30 sedentary adults completed each of three conditions : 6 h of uninterrupted sitting ( SIT ) , SIT plus 30 min of moderate-intensity treadmill walking in the morning ( ONE ) , and SIT plus six hourly 5-min microbouts of moderate-intensity treadmill walking ( MICRO ) . Self-perceived energy , mood , and appetite were assessed with visual analog scales . Vigor and fatigue were assessed with the Profile of Mood State question naire . Cognitive function was measured using a flanker task and the Comprehensive Trail Making Test . Intervention effects were tested using linear mixed models . Results Both ONE and MICRO increased self-perceived energy and vigor compared to SIT ( p improved mood , decreased levels of fatigue and reduced food cravings at the end of the day compared to SIT ( p Cognitive function was not significantly affected by condition . Conclusions In addition to the beneficial impact of physical activity on levels of energy and vigor , spreading out physical activity throughout the day improved mood , decreased feelings of fatigue and affected appetite . Introducing short bouts of activity during the workday of sedentary office workers is a promising approach to improve overall well-being at work without negatively impacting cognitive performance . Trial registration NCT02717377 , registered 22 March 2016", "Even when adults meet physical activity guidelines , sitting for prolonged periods can compromise metabolic health . Television ( TV ) time and objective measurement studies show deleterious associations , and breaking up sedentary time is beneficial . Sitting time , TV time , and time sitting in automobiles increase premature mortality risk . Further evidence from prospect i ve studies , intervention trials , and population -based behavioral studies is required", "The aim of this study was to test the hypothesis that chronic physical exercise improves attentional control in young healthy participants . To do this , we compared the performance of physically active and passive participants in the Attentional Network Task , which allows for the assessment of the executive , orienting and alerting networks . The results showed a selective positive effect of exercise on the executive network . These results extend the evidence gathered in children , older adults and certain clinical population s suggesting that exercise can also improve attentional control in healthy young adults", "Background Evidence suggests a link between sedentary behaviours and depressive symptoms . Mechanisms underlying this relationship are not understood , but inflammatory processes may be involved . Autonomic and inflammatory responses to stress may be heightened in sedentary individuals contributing to risk , but no study has experimentally investigated this . Aims To examine the effect of sedentary time on mood and stress responses using an experimental design . Method Forty-three individuals were assigned to a free-living sedentary condition and to a control condition ( usual activity ) in a cross-over , r and omised fashion and were tested in a psychophysiology laboratory after spending 2 weeks in each condition . Participants completed mood question naires ( General Health Question naire and Profile of Mood States ) and wore a motion sensor for 4 weeks . Results Sedentary time increased by an average of 32 min/day ( P = 0.01 ) during the experimental condition compared with control . Being sedentary result ed in increases in negative mood independent of changes in moderate to vigorous physical activity ( ΔGHQ = 6.23 , ΔPOMS = 2.80 ) . Mood disturbances were associated with greater stress-induced inflammatory interleukin-6 ( IL-6 ) responses ( β = 0.37 ) . Conclusions Two weeks of exposure to greater free-living sedentary time result ed in mood disturbances independent of reduction in physical activity . Stress-induced IL-6 responses were associated with changes in mood ", "Purpose This study aim ed to examine the effects of self-selected low-intensity walking on an active workstation on executive functions ( EF ) in young and middle-age adults . Methods Using a within-subjects design , 32 young ( 20.6 ± 2.0 yr ) and 26 middle-age ( 45.6 ± 11.8 yr ) adults performed low-intensity treadmill walking and seated control conditions in r and omized order on separate days , while completing an EF test battery . EF was assessed using modified versions of the Stroop ( inhibition ) , Sternberg ( working memory ) , Wisconsin Card Sorting ( cognitive flexibility ) , and Tower of London ( global EF ) cognitive tasks . Behavioral performance outcomes were assessed using composite task z-scores and traditional measures of reaction time and accuracy . Average HR and step count were also measured throughout . Results The expected task difficulty effects were found for reaction time and accuracy . No significant main effects or interactions as a function of treadmill walking were found for tasks assessing global EF and the three individual EF domains . Accuracy on the Tower of London task was slightly impaired during slow treadmill walking for both age-groups . Middle-age adults displayed longer planning times for more difficult conditions of the Tower of London during walking compared with sitting . A 50-min session of low-intensity treadmill walking on an active workstation result ed in accruing approximately 4500 steps . Conclusions These findings suggest that executive function performance remains relatively unaffected while walking on an active workstation , further supporting the use of treadmill workstations as an effective approach to increase physical activity and reduce sedentary time in the workplace", "CONTEXT Current public health campaigns to reduce obesity and type 2 diabetes have largely focused on increasing exercise , but have paid little attention to the reduction of sedentary behaviors . OBJECTIVE To examine the relationship between various sedentary behaviors , especially prolonged television ( TV ) watching , and risk of obesity and type 2 diabetes in women . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study conducted from 1992 to 1998 among women from 11 states in the Nurses ' Health Study . The obesity analysis included 50 277 women who had a body mass index ( BMI ) of less than 30 and were free from diagnosed cardiovascular disease , diabetes , or cancer and completed questions on physical activity and sedentary behaviors at baseline . The diabetes analysis included 68 497 women who at baseline were free from diagnosed diabetes mellitus , cardiovascular disease , or cancer . MAIN OUTCOME MEASURES Onset of obesity and type 2 diabetes mellitus . RESULTS During 6 years of follow-up , 3757 ( 7.5 % ) of 50 277 women who had a BMI of less than 30 in 1992 became obese ( BMI > or = 30 ) . Overall , we documented 1515 new cases of type 2 diabetes . Time spent watching TV was positively associated with risk of obesity and type 2 diabetes . In the multivariate analyses adjusting for age , smoking , exercise levels , dietary factors , and other covariates , each 2-h/d increment in TV watching was associated with a 23 % ( 95 % confidence interval [ CI ] , 17%-30 % ) increase in obesity and a 14 % ( 95 % CI , 5%-23 % ) increase in risk of diabetes ; each 2-h/d increment in sitting at work was associated with a 5 % ( 95 % CI , 0%-10 % ) increase in obesity and a 7 % ( 95 % CI , 0%-16 % ) increase in diabetes . In contrast , st and ing or walking around at home ( 2 h/d ) was associated with a 9 % ( 95 % CI , 6%-12 % ) reduction in obesity and a 12 % ( 95 % CI , 7%-16 % ) reduction in diabetes . Each 1 hour per day of brisk walking was associated with a 24 % ( 95 % CI , 19%-29 % ) reduction in obesity and a 34 % ( 95 % CI , 27%-41 % ) reduction in diabetes . We estimated that in our cohort , 30 % ( 95 % CI , 24%-36 % ) of new cases of obesity and 43 % ( 95 % CI , 32%-52 % ) of new cases of diabetes could be prevented by adopting a relatively active lifestyle ( or = 30 min/d of brisk walking ) . CONCLUSIONS Independent of exercise levels , sedentary behaviors , especially TV watching , were associated with significantly elevated risk of obesity and type 2 diabetes , whereas even light to moderate activity was associated with substantially lower risk . This study emphasizes the importance of reducing prolonged TV watching and other sedentary behaviors for preventing obesity and diabetes", "Background Prolonged sitting is associated with cardiometabolic and vascular disease . Despite emerging evidence regarding the acute health benefits of interrupting prolonged sitting time , the effectiveness of different modalities in older adults ( who sit the most ) is unclear . Methods In preparation for a future r and omized controlled trial , we enrolled 10 sedentary , overweight or obese , postmenopausal women ( mean age 66 years ±9 ; mean body mass index 30.6 kg/m2 ±4.2 ) in a 4-condition , 4-period crossover feasibility pilot study in San Diego to test 3 different sitting interruption modalities design ed to improve glucoregulatory and vascular outcomes compared to a prolonged sitting control condition . The interruption modalities included : a ) 2 minutes st and ing every 20 minutes ; b ) 2 minutes walking every hour ; and c ) 10 minutes st and ing every hour . During each 5-hr condition , participants consumed two identical , st and ardized meals . Blood sample s , blood pressure , and heart rate were collected every 30 minutes . Endothelial function of the superficial femoral artery was measured at baseline and end of each 5-hr condition using flow-mediated dilation ( FMD ) . Participants completed each condition on separate days , in r and omized order . This feasibility pilot study was not powered to detect statistically significant differences in the various outcomes , however , analytic methods ( mixed models ) were used to test statistical significance within the small sample size . Results Nine participants completed all 4 study visits , one participant completed 3 study visits and then was lost to follow up . Net incremental area under the curve ( iAUC ) values for postpr and ial plasma glucose and insulin during the 5-hr sitting interruption conditions were not significantly different compared to the control condition . Exploratory analyses revealed that the 2-minute st and ing every 20 minutes and the 2-minute walking every hour conditions were associated with a significantly lower glycemic response to the second meal compared to the first meal ( i.e. , condition-matched 2-hour post-lunch glucose iAUC was lower than 2-hour post-breakfast glucose iAUC ) that withstood Bonferroni correction ( p = 0.0024 and p = 0.0084 , respectively ) . Using allometrically scaled data , the 10-minute st and ing every hour condition result ed in an improved FMD response , which was significantly greater than the control condition after Bonferroni correction ( p = 0.0033 ) . Conclusion This study suggests that brief interruptions in prolonged sitting time have modality-specific glucoregulatory and vascular benefits and are feasible in an older adult population . Larger laboratory and real-world intervention studies of pragmatic and effective methods to change sitting habits are needed . Trial registration Clinical Trials.gov NCT02743286", "OBJECTIVES To compare acute cognitive effects following bouts of st and ing ( ST AND ) , cycling ( CYCLE ) and walking ( WALK ) to a sit-only ( SIT ) condition . DESIGN R and omized cross-over full-factorial study . METHODS Nine overweight ( BMI = 29±3kg/m2 ) adults ( 30±15years ; 7 females , 2 males ) completed four conditions ( SIT , ST AND , WALK and CYCLE ) across a 6h period with a 7days washout period between conditions . SIT consisted of uninterrupted sitting . Experimental conditions included intermittent bouts of st and ing ( ST AND ) , cycling ( CYCLE ) and walking ( WALK ) . A cognitive performance battery ( Cogstate ) was completed twice in a seated position following bouts of st and ing and light-intensity physical activity . Mixed-effects models compared between-condition differences in st and ardized score ( z-score ) , accuracy ( % ) , and speed ( log10ms ) . RESULTS Cognitive performance z-score and accuracy measures were higher during ST AND , CYCLE and WALK ( P of st and ing or light-intensity cycling and walking may improve acute cognitive performance ", "IMPORTANCE Sedentary behaviors and physical inactivity are not only increasing worldwide but also are critical risk factors for adverse health outcomes . Yet , few studies have examined the effects of sedentary behavior on cognition or the long-term role of either behavior in early to middle adulthood . OBJECTIVE To investigate the association between 25-year patterns of television viewing and physical activity and midlife cognition . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve study of 3247 adults ( black and white races ; aged 18 - 30 years ) enrolled in the Coronary Artery Risk Development in Young Adults ( CARDIA ) Study ( March 25 , 1985 , to August 31 , 2011 ) . Data analysis was performed June 1 , 2014 , through April 15 , 2015 . MAIN OUTCOMES AND MEASURES We assessed television viewing and physical activity at repeated visits ( ≥3 assessment s ) over 25 years using a vali date d question naire . A 25-year pattern of high television viewing was defined as watching TV above the upper baseline quartile ( > 3 hours/d ) for more than two-thirds of the visits , and a 25-year pattern of low physical activity was defined as activity levels below the lower , sex-specific baseline quartile for more than two-thirds of the of the visits . We evaluated cognitive function at year 25 using the Digit Symbol Substitution Test ( DSST ) , Stroop test , and Rey Auditory Verbal Learning Test . RESULTS At baseline , the mean ( SD ) age of the 3247 study participants was 25.1 ( 3.6 ) years , 1836 ( 56.5 % ) were female , 1771 ( 54.5 % ) were white , and 3015 ( 92.9 % ) had completed at least high school . Compared with participants with low television viewing , those with high television viewing during 25 years ( 353 of 3247 [ 10.9 % ] ) were more likely to have poor cognitive performance ( the DSST and Stroop test , with findings reported as adjusted odds ratio ( 95 % CI ) : DSST , 1.64 ( 1.21 - 2.23 ) and Stroop test , 1.56 ( 1.13 - 2.14 ) , but not the Rey Auditory Verbal Learning Test , adjusted for age , race , sex , educational level , smoking , alcohol use , body mass index , and hypertension . Low physical activity during 25 years in 528 of 3247 participants ( 16.3 % ) was significantly associated with poor performance on the DSST , 1.47 ( 1.14 - 1.90 ) . Compared with participants with low television viewing and high physical activity , the odds of poor performance were almost 2 times higher for adults with both high television viewing and low physical activity in 107 of 3247 ( 3.3 % ) ( DSST , 1.95 [ 1.19 - 3.22 ] , and Stroop test , 2.20 [ 1.36 - 3.56 ] ) . CONCLUSIONS AND RELEVANCE High television viewing and low physical activity in early adulthood were associated with worse midlife executive function and processing speed . This is one of the first studies to demonstrate that these risk behaviors may be critical targets for prevention of cognitive aging even before middle age", "PURPOSE This study aim ed to examine whether reductions in sitting time through alternating 30-min bouts of sitting and st and ing can reduce postpr and ial glucose , insulin , and triglyceride responses . METHODS Twenty-three overweight/obese sedentary office workers ( 17 males and six females ; mean ± SD : age , 48.2 ± 7.9 yr ; body mass index , 29.6 ± 4.0 kg · m(-2 ) ) undertook two short-term ( 5 d ) experimental conditions in an equal , r and omized ( 1:1 ) order . In a simulated office environment , participants performed typical occupational tasks for 8 h · d(-1 ) while in a 1 ) seated work posture ( control condition ) or 2 ) interchanging between a seated and st and ing work posture every 30 min using an electric , height-adjustable workstation ( intervention condition ) . Fasting and postpr and ial blood sample s after a mixed test drink were collected hourly for 4 h on days 1 and 5 of each condition to assess serum insulin , plasma glucose , and triglycerides . Dietary intake ( kJ · d(-1 ) ) and physical activity were st and ardized during each condition . The trial was registered with the Australian New Zeal and Clinical Trials Registry ( ACTRN12611000632998 ) . RESULTS After adjustment for time ( days 1 and 5 ) , incremental area under the analyte time curve differed significantly between conditions for plasma glucose ( P = 0.007 ) but not for serum insulin or plasma triglycerides . Adjusted mean glucose incremental area under the analyte time curve was lowered by 11.1 % after the intervention condition ( 6.38 mM · h(-1 ) ( confidence interval , 5.04 - 7.71 ) ) relative to the control condition ( 7.18 mM · h(-1 ) ( confidence interval , 5.85 - 8.52 ) ) . No temporal changes ( days 1 vs 5 ) between conditions were observed . CONCLUSIONS Alternating st and ing and sitting in 30-min bouts results in modest beneficial effects on postpr and ial glucose responses in overweight/obese office workers", "Purpose : To examine the effects of a free-living , sedentary-inducing intervention on cognitive function . Design : R and omized controlled , parallel group intervention . Setting : University campus . Participants : Thirty-three young adults ( n = 23 intervention ; n = 10 control ) . Measures : The intervention group was asked to eliminate all exercise and minimize steps to ≤5000 steps/day for 1 week , whereas the control group was asked to continue normal physical activity ( PA ) levels for 1 week . Both groups completed a series of 8 cognitive function assessment s ( assessing multiple parameters of cognition ) preintervention and immediately postintervention . The intervention group was asked to resume normal PA levels for 1 week postintervention and completed the cognitive assessment s for a third time at 2 weeks postintervention . Analysis : Split-plot repeated- measures analysis of variance . Results : The results of our statistical analyses showed that the group × time interaction effect was not significant ( P > .05 ) for any of the evaluated cognitive parameters . Conclusion : These findings demonstrate the need for future experimental investigations of sedentary behavior to better underst and its effects on cognitive function . However , although previous work has demonstrated favorable effects of acute and chronic PA on cognitive function , our findings suggest that a 1-week period of reduced PA does not detrimentally affect cognitive function , which may have encouraging implication s for individuals going through a temporary relapse in PA", "Abstract Sedentary behaviour is increasing and has been identified as a potential significant health risk , particularly for desk-based employees . The development of sit-st and workstations in the workplace is one approach to reduce sedentary behaviour . However , there is uncertainty about the effects of sit-st and workstations on cognitive functioning . A sample of 36 university staff participated in a within-subjects r and omised control trial examining the effect of sitting vs. st and ing for one hour per day for five consecutive days on attention , information processing speed , short-term memory , working memory and task efficiency . The results of the study showed no statistically significant difference in cognitive performance or work efficiency between the sitting and st and ing conditions , with all effect sizes being small to very small ( all ds cognitive performance . Practitioner Summary : Although it has been reported that the use of sit-st and desks may help offset adverse health effects of prolonged sitting , there is scant evidence about changes in productivity . This r and omised control study showed that there was no difference between sitting and st and ing for one hour on cognitive function or task efficiency in university staff", "Background : A number of cross‐sectional studies have suggested that higher levels of sedentary behavior ( SB ) are associated with worse cognitive abilities in older age . There is a paucity of longitudinal studies investigating this relationship utilizing objective ly assessed SB . This study investigated the relationship between objective ly assessed SB and future cognitive abilities in a cohort of older adults . Methods : A longitudinal study over 22.12 ± 1.46 months including 285 community‐dwelling older adults across 14 regions in Taiwan was undertaken . Cognitive ability was ascertained using a Chinese version of the Ascertain Dementia 8‐item Question naire ( AD8 ) and SB captured by 7 days accelerometer data . Multivariable negative binomial regression models adjusted for confounders were undertaken . Results : 274 community‐dwelling older adults finished the study ( age = 74.6 ± 6.2 , % female = 54.4 % ) . At baseline , 20.1 % ( n = 55 ) , 48.5 % ( n = 133 ) and 31.4 % ( n = 86 ) of the sample engaged in high ( 11 + h ) , medium ( 7–10.99 h ) and low ( of SB respectively . In the fully adjusted model , higher levels of SB were associated with an increased risk of worse cognitive ability at follow up ( adjusted rate ratio (ARR)1.09 ( 95%CI:1.00–1.19 ) ) , with the strongest relationship evident in those engaging in over 11 h of SB ( ARR 2.27 ( 95%CI:1.24–4.16 ) ) . The relationship remained evident after adjusting for depressive symptoms and physical activity . Conclusion : Our data suggests that objective ly assessed SB , particularly when over 11 h a day , is independently associated with worse cognitive ability over a two year period . Our data adds to the pressing reasons to reduced SB in older age . HighlightsFirst prospect i ve study to investigate objective ly sedentary behavior ( SB ) and cognition in older adults . Higher levels of objective SB were independently associated with worse cognitive ability over two years . This relationship was most pronounced in older people spending over 11 h a day being sedentary" ]	41189e88-06ff-11f0-808a-c43d1ab1c353
BACKGROUND Schizophrenia often presents in adolescence , but current treatment guidelines are based largely on studies of adults with psychosis . Over the past decade , the number of studies on treatment of adolescent-onset psychosis has increased . The current systematic review collates and critiques evidence obtained on the use of various atypical antipsychotic medications for adolescents with psychosis . OBJECTIVES To investigate the effects of atypical antipsychotic medications in adolescents with psychosis . We review ed in separate analyses various comparisons of atypical antipsychotic medications with placebo or a typical antipsychotic medication or another atypical antipsychotic medication or the same atypical antipsychotic medication but at a lower dose . SEARCH METHODS We search ed the Cochrane Schizophrenia Group Register ( October 2011 ) , which is based on regular search es of BIOSIS , CENTRAL , CINAHL , EMBASE , MEDLINE and PsycINFO . We inspected references of all identified studies and contacted study authors and relevant pharmaceutical companies to ask for more information . SELECTION CRITERIA We included all relevant r and omised controlled trials ( RCTs ) that compared atypical antipsychotic medication with placebo or another pharmacological intervention or with psychosocial interventions , st and ard psychiatric treatment or no intervention in children and young people aged 13 to 18 years with a diagnosis of schizophrenia , schizoaffective disorder , acute and transient psychoses or unspecified psychosis . We included studies published in English and in other language s that were available in st and ardised data bases . DATA COLLECTION AND ANALYSIS Review authors AK and SSD selected the studies , rated the quality of the studies and performed data extraction . For dichotomous data , we estimated risk ratios ( RRs ) with 95 % confidence intervals ( CIs ) using a fixed-effect model . When possible , for binary data presented in the ' Summary of findings ' table , we calculated illustrative comparative risks . We summated continuous data using the mean difference ( MD ) . Risk of bias was assessed for included studies . MAIN RESULTS We included 13 RCTs , with a total of 1112 participants . We found no data on service utilisation , economic outcomes , behaviour or cognitive response . Trials were classified into the following groups . 1 . Atypical antipsychotics versus placebo : Only two studies compared one atypical antipsychotic medication with placebo . In one study , the number of non-responders treated with olanzapine was not different from the number treated with placebo ( 1 RCT , n = 107 , RR 0.84 , 95 % CI 0.65 to 1.10 ) ; however , significantly more ( 57 % vs 32 % ) people left the study early ( 1 RCT , n = 107 , RR 0.56 , 95 % CI 0.36 to 0.87 ) from the placebo group compared with the olanzapine group . With regard to adverse effects , young people treated with aripiprazole had significantly lower serum cholesterol compared with those given placebo ( 1 RCT , n = 302 , RR 3.77 , 95 % CI 1.88 to 7.58 ) . 2 . Atypical antipsychotics versus typical antipsychotics : When the findings of all five trials comparing atypical antipsychotic medications with a typical antipsychotic medication were collated , no difference in the mean end point Brief Psychiatric Rating Scale ( BPRS ) score was noted between the two arms ( 5 RCTs , n = 236 , MD -1.08 , 95 % CI -3.08 to 0.93 ) . With regard to adverse effects , the mean end point serum prolactin concentration was much higher than the reference range for treatment with risperidone , olanzapine and molindone in one of the studies . However , fewer adolescents who were receiving atypical antipsychotic medications left the study because of adverse effects ( 3 RCTs , n = 187 , RR 0.65 , 95 % CI 0.36 to 1.15 ) or for any reason ( 3 RCTs , n = 187 , RR 0.62 , 95 % CI 0.39 to 0.97).3 . One atypical antipsychotic versus another atypical antipsychotic : The mean end point BPRS score was not significantly different for people who received risperidone compared with those who received olanzapine ; however , the above data were highly skewed . Overall no difference was noted in the number of people leaving the studies early because of any adverse effects between each study arm in the three studies comparing olanzapine and risperidone ( 3 RCTs , n = 130 , RR 1.15 , 95 % CI 0.44 to 3.04 ) . Specific adverse events were not reported uniformly across the six different studies included in this section of the review ; therefore it was difficult to do a head-to-head comparison of adverse events for different atypical antipsychotic medications.4 . Lower-dose atypical antipsychotic versus st and ard/higher-dose atypical antipsychotic : Three studies reported comparisons of lower doses of the atypical antipsychotic medication with st and ard/higher doses of the same medication . One study reported better symptom reduction with a st and ard dose of risperidone as compared with a low dose ( 1 RCT , n = 257 , RR -8.00 , 95 % CI -13.75 to -2.25 ) . In another study , no difference was reported in the number of participants not achieving remission between the group receiving 10 mg/d and those who received 30 mg/d of aripiprazole ( 1 RCT , n = 196 , RR 0.84 , 95 % CI 0.48 to 1.48 ) . Similarly in the other study , authors reported no statistically significant difference in clinical response between the two groups receiving lower-dose ( 80 mg/d ) and higher-dose ( 160 mg/d ) ziprasidone , as reflected by the mean end point BPRS score ( 1 RCT , n = 17 , MD -4.40 , 95 % CI -19.20 to 10.40 ) . AUTHORS ' CONCLUSIONS No convincing evidence suggests that atypical antipsychotic medications are superior to typical medications for the treatment of adolescents with psychosis . However , atypical antipsychotic medications may be more acceptable to young people because fewer symptomatic adverse effects are seen in the short term . Little evidence is available to support the superiority of one atypical antipsychotic medication over another , but side effect profiles are different for different medications . Treatment with olanzapine , risperidone and clozapine is often associated with weight gain . Aripiprazole is not associated with increased prolactin or with dyslipidaemia . Adolescents may respond better to st and ard-dose as opposed to lower-dose risperidone , but for aripiprazole and ziprasidone , lower doses may be equally effective . Future trials should ensure uniform ways of reporting	[ "Objective : To examine if a cognitive remediation program could be a positive supplement to a psychoeducational treatment program for adolescents with early onset psychosis", "The first double-blind placebo-controlled clinical trial of an atypical neuroleptic medication is being conducted in symptomatic treatment-seeking patients meeting new diagnostic criteria for a putative prodromal syndrome . This identifies them as being at high risk for developing psychosis in the near future . The study aims include prevention of psychosis onset and disability , as well as palliation of ongoing symptomatology . This report presents the study rationale and design . Recent studies will be review ed that have advanced our knowledge about the early course of schizophrenia and our ability to predict onset prospect ively , advances that have rendered prodromal intervention research feasible and ethical . The study design has many novel features . It tests for prevention versus delay in psychosis onset , as well as for efficacy and safety in a newly defined clinical population . This has required the development of innovative clinical research assessment instruments and a new operational definition of psychosis onset . The integration of these novel elements into an otherwise typical clinical trial design is detailed . The companion report will address sample recruitment and the clinical phenomenology at baseline of this putative \" prodromal \" entity", "Atendency to extract spurious , message-like meaning from meaningless noise was assessed as a risk factor leading to schizophrenia-spectrum disorders by assessing word length of speech illusions elicited by multispeaker babble in 43 people with prodromal symptoms . These individuals were r and omised to olanzapine v. placebo groups during year 1 followed by no pharmacological treatment for those with no disorder conversion during year 2 . A time-dependent Cox regression analysis of conversion to schizophrenia-spectrum disorder revealed a significant interaction between condition ( olanzapine v. no drug ) and length of speech illusion , with the latter strongly predicting subsequent conversion during medication-free intervals but not during olanzapine treatment", "OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered \" mildly ill \" according to the CGI approximately corresponded to a PANSS total score of 58 , \" moderately ill \" to a PANSS of 75 , \" markedly ill \" to a PANSS of 95 and severely ill to a PANSS of 116 . To be \" minimally improved \" according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating \" much improved \" were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate", "OBJECTIVE To investigate whether intercessory prayer had an effect on the outcomes of a group of children with psychiatric conditions , using a triple blind r and omized study design . CONCLUSION This study was unable to show any additional benefits for patients who received intercessory prayer compared to those who received treatment as usual", "OBJECTIVE To assess olanzapine 's efficacy and tolerability in adolescents with schizophrenia . METHOD One hundred seven inpatient and outpatient adolescents ( olanzapine , n = 72 , mean age 16.1 years ; placebo , n = 35 , mean age 16.3 years ) with schizophrenia participated in this r and omized ( 2:1 ) , international , multisite , industry-sponsored trial . All patients met DSM-IV-TR criteria for schizophrenia , and they were treated for up to 6 weeks with flexible doses of olanzapine ( 2.5 - 20.0 mg/day ) or placebo . Last-observation-carried-forward mean changes from baseline to endpoint on the anchored version of the Brief Psychiatric Rating Scale for Children , Clinical Global Impression Scale-Severity of Illness , and Positive and Negative Syndrome Scale ( PANSS ) were assessed . RESULTS More olanzapine-treated versus placebo-treated patients completed the trial ( 68.1 % versus 42.9 % , p = .020 ) . Compared with placebo-treated patients , olanzapine-treated adolescents had significantly greater improvement in Brief Psychiatric Rating Scale for Children total ( p = .003 ) , Clinical Global Impressions Scale-Severity of Illness ( p = .004 ) , PANSS total ( p = .005 ) , and PANSS positive scores ( p = .002 ) . Olanzapine-treated patients gained significantly more baseline-to-endpoint weight ( 4.3 kg versus 0.1 kg , p olanzapine-treated versus placebo-treated patients gained 7 % or greater of their body weight at any time during treatment ( 45.8 % versus 14.7 % , p = .002 ) . Prolactin and triglyceride mean baseline-to-endpoint changes were significantly higher in olanzapine-treated versus placebo-treated adolescents . The incidence of treatment-emergent significant changes in fasting glucose , cholesterol , or triglycerides did not differ between the groups at endpoint , but significantly more olanzapine-treated patients had high triglycerides at any time during treatment . CONCLUSIONS Olanzapine-treated adolescents with schizophrenia experienced significant symptom improvement . Significant increases in weight , triglycerides , uric acid , most liver function tests , and prolactin were observed during olanzapine treatment . Clinical trial registration information-Olanzapine Versus Placebo in the Treatment of Adolescents With Schizophrenia . URL : http://www . clinical trials.gov . Unique identifier : NCT00051298", "BACKGROUND This paper investigates the durability of the effects of cognitive remediation therapy ( CRT ) . In a r and omised control trial , CRT was compared with a control therapy ( intensive occupational therapy activities ) , matched for length of therapist contact . The main three cognitive outcomes , ( i ) number of categories achieved on the Wisconsin Card Sort Test , ( ii ) age-scaled score on the Digit Span subtest of the WAIS-R , and ( iii ) mean number of moves on the Tower of London test , were chosen because they are known to be problematic in schizophrenia . In addition , a wide variety of other outcomes ( symptoms , social functioning , self-esteem and cognition ) were assessed . At the end of treatment , CRT conferred a benefit to people with schizophrenia in cognition and self-esteem [ Schizophr . Bull . 25 ( 1999 ) 291 ] . This study investigates these outcomes 6 months after the therapies were withdrawn . METHOD Participants were assessed at baseline , posttreatment and 6-month follow-up ( n=17 for the CRT group ; n=16 for the control therapy group ) . In addition to the functioning measures , data on use of services and cost of therapy were collected . RESULTS The effects of CRT on cognition were still apparent at follow-up , particularly in the memory domain . When these cognitive improvements reached a criterion threshold , there were also improvements in social behaviour and symptoms . The gains made in self-esteem disappeared following the withdrawal of therapy . The economic analysis showed overall reductions in the care packages of both patient groups but there was a significant increase in day-care costs for patients who have received CRT . This additional use of day care may confer further advantages to the CRT group , such as improved social functioning and quality of life . CONCLUSIONS The overall results of this first trial of a novel CRT approach have produced encouraging results which merit further investigation", "The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas", "An ongoing study of the phenomenology , genetics , neuropsychology , physiology ( eye tracking , autonomic responsivity ) , neuroimaging , biochemistry , and pharmacology of childhood-onset schizophrenia is described , and pilot data are presented for the first 22 subjects . Differentiation from autism \" spectrum \" disorders and other poorly defined , severe neurodevelopmental disorders is needed . Eye tracking and autonomic results are similar to patterns seen in later-onset schizophrenia and possibly more striking . Magnetic resonance imaging showed larger left frontal ventricular horn area for the schizophrenia subjects , larger left cau date , and lack of normal cau date asymmetry . Fluorodeoxyglucose positron emission tomography during an auditory continuous performance task revealed decreased right parietal/occipital glucose metabolic rate in the schizophrenia subjects , which may be secondary to poor attentional performance , and increased glucose metabolic rate in three left frontal regions , a left parietal region , and the right putamen . Clozapine has been effective and well tolerated in an open trial with 12 adolescents who responded poorly to typical neuroleptics ; 16 subjects have been enrolled in a double-blind comparison of haloperidol and clozapine . Longitudinal study of this narrowly defined and possibly more homogeneous group of very early-onset schizophrenia subjects will be relevant to current neurodevelopmental theories addressing the role of puberty , progression of pathology , and continuity or discontinuity with later-onset schizophrenia", "OBJECTIVE There is a limited evidence base to guide treatment of children and adolescents with nonaffective psychoses because few comparative studies of first-line second-generation antipsychotics ( SGAs ) have been undertaken . To plan the design of a subsequent r and omized controlled trial ( RCT ) , the authors conducted this pilot study to demonstrate the feasibility of the treatment and measurement protocol s. METHOD Thirty children and adolescents ( 20 males , 10 females ) , ages 10 - 18 years , who met unmodified Diagnostic and Statistical Manual of Mental Disorders , 4th edition ( DSM-IV ) criteria for a schizophrenia-spectrum disorder ( schizophrenia , schizoaffective , schizophreniform , psychotic disorder not otherwise specified ) were r and omized to receive 12 weeks of open-label , flexibly dosed treatment with either risperidone ( mean [ st and ard deviation , SD ] dose = 3.4 mg [ 1.5 ] ) , olanzapine ( mean [ SD ] dose = 14.0 mg [ 4.6 ] ) or quetiapine ( mean [ SD ] dose = 611 mg [ 253.4 ] ) . RESULTS Twenty one ( 70 % ) of 30 subjects completed the study . There was no overall statistically significant difference with regard to reduction in Positive and Negative Syndrome Scale ( PANSS ) total scores in treatment efficacy observed ( F((2,24 ) ) = 3.13 , p = 0.06 ) . However , the possibility of a large differential treatment effect with regard to change in PANSS total scores favoring risperidone relative to quetiapine ( risperidone vs. quetiapine , d = 1.10 [ 95 % confidence interval , CI , 0.09 - 2.01 ] ) was suggested by the point estimate . CONCLUSIONS These preliminary data , viewed together with the extant literature , suggest that a future larger RCT with only two treatment arms may be warranted to establish whether there is a clinical ly significant differential treatment effect between risperidone and quetiapine for children and adolescents with nonaffective psychoses . Additional challenges and considerations for mounting a larger RCT are explored", "BACKGROUND The relative effectiveness of second-generation ( atypical ) antipsychotic drugs as compared with that of older agents has been incompletely addressed , though newer agents are currently used far more commonly . We compared a first-generation antipsychotic , perphenazine , with several newer drugs in a double-blind study . METHODS A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and r and omly assigned to receive olanzapine ( 7.5 to 30 mg per day ) , perphenazine ( 8 to 32 mg per day ) , quetiapine ( 200 to 800 mg per day ) , or risperidone ( 1.5 to 6.0 mg per day ) for up to 18 months . Ziprasidone ( 40 to 160 mg per day ) was included after its approval by the Food and Drug Administration . The primary aim was to delineate differences in the overall effectiveness of these five treatments . RESULTS Overall , 74 percent of patients discontinued the study medication before 18 months ( 1061 of the 1432 patients who received at least one dose ) : 64 percent of those assigned to olanzapine , 75 percent of those assigned to perphenazine , 82 percent of those assigned to quetiapine , 74 percent of those assigned to risperidone , and 79 percent of those assigned to ziprasidone . The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine ( P risperidone ( P=0.002 ) group , but not in the perphenazine ( P=0.021 ) or ziprasidone ( P=0.028 ) group . The times to discontinuation because of intolerable side effects were similar among the groups , but the rates differed ( P=0.04 ) ; olanzapine was associated with more discontinuation for weight gain or metabolic effects , and perphenazine was associated with more discontinuation for extrapyramidal effects . CONCLUSIONS The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons . Olanzapine was the most effective in terms of the rates of discontinuation , and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine , risperidone , and ziprasidone . Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism", "BACKGROUND Effective treatments for adolescent schizophrenia are needed . AIMS To compare efficacy and safety of two dosing regimens of risperidone . METHOD Double-blind , 8-week study . Patients , 13 - 17 years , with an acute episode of schizophrenia , r and omised 1:1 to risperidone 1.5 - 6.0 mg/day ( regimen A ; n=125 ) or 0.15 - 0.6 mg/day ( regimen B ; n=132 ) . TRIAL REGISTRATION NUMBER NCT00034749 . RESULTS Mean total Positive and Negative Syndrome Scale ( PANSS ) score improved significantly ( P Treatment-emergent adverse events occurred in 74 % ( regimen A ) and 65 % ( regimen B ) of patients ; 4 % of patients overall discontinued for adverse events . Mean change in body weight was 3.2 kg ( s.d.=3.49 ) for regimen A and 1.7 kg ( s.d.=3.29 ) for regimen B. CONCLUSIONS Adolescent patients in the regimen A group showed greater improvement in total PANSS compared with the regimen B group . Treatment was well tolerated", "Background : The prevalence of obsessive-compulsive symptoms ( OCS ) in patients with schizophrenia is relatively high . Antipsychotics have been found to influence OCS . Objective : To determine whether induction or severity of OCS differs during treatment with olanzapine or risperidone in young patients with early psychosis . Methods : One hundred twenty-two patients with a Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition diagnosis of schizophrenia , schizoaffective disorder , or schizophreniform disorder were r and omized in a double-blind design to groups of 6 weeks ' treatment with olanzapine ( n = 59 ) or risperidone ( n = 63 ) , with a mean dose of 11.3 mg olanzapine and 3.0 mg risperidone at 6 weeks . Primary outcome measures were the mean baseline-to-endpoint change in total score on the Yale-Brown Obsessive-Compulsive Scale ( Y-BOCS ) . Results : Treatment with olanzapine was associated with greater decreases in Y-BOCS total score than treatment with risperidone in total group ( N = 122 : -2.2 vs -0.3 , z = -2.651 , P Y-BOCS total score greater than 0 ( n = 58 : -5.1 vs -0.4 , z = -2.717 , P Y-BOCS total score greater than 10 ( n = 29 : -7.1 vs -0.6 , z = -2.138 , P = 0.032 ) . Conclusions : In this r and omized , 6-week , double-blind trial , we found a significant and clinical ly relevant difference in decrease in Y-BOCS scores favoring olanzapine compared with risperidone", "BACKGROUND The present study evaluated the effectiveness and safety of clozapine versus \" high-dose \" olanzapine in treatment-refractory adolescents with schizophrenia . METHODS Children , ages 10 - 18 years , who met DSM-IV criteria for schizophrenia and who were resistant or intolerant to at least two antipsychotic drugs were r and omized to receive 12 weeks of double-blind flexibly dosed treatment with clozapine ( n = 18 ) or \" high-dose \" olanzapine ( up to 30 mg/day ) ( n = 21 ) . The primary efficacy measure was response ( improvement ) , defined as a decrease of 30 % or more in total Brief Psychiatric Rating Scale score from baseline and a Clinical Global Impression Scale improvement rating of \" 1 \" ( very much improved ) or \" 2 \" ( much improved ) . RESULTS Significantly more clozapine-treated adolescents met response criteria ( 66 % ) compared with olanzapine-treated subjects ( 33 % ) . Clozapine was superior to olanzapine in terms of reduction of the psychosis cluster scores and negative symptoms from baseline to end point . However , both treatments were associated with significant weight-gain and related metabolic abnormalities . CONCLUSIONS This double-blind r and omized comparison of two second-generation antipsychotic drugs for treatment-refractory adolescents with schizophrenia supports clozapine as the agent of choice . The development of interventions to limit weight gain and metabolic side effects are needed to enhance the risk-benefit profile for both study treatments", "This pilot study was undertaken to estimate the acute antipsychotic effect size and side effect propensity of risperidone and olanzapine in the pediatric population , in comparison to haloperidol , a conventional antipsychotic with established efficacy . Risperidone and olanzapine are widely used as first-line treatments to ameliorate psychotic symptoms in youth , but their abilities to specifically treat children and adolescents presenting due to psychotic symptoms have not been rigorously studied . Subjects , selected because of prominent positive psychotic symptoms , were r and omly assigned to double-blind , parallel treatment with risperidone , olanzapine , or haloperidol for 8 weeks . The primary outcome was reduction in the Brief Psychiatric Rating Scale for Children total score from baseline to termination . An exploratory , descriptive analysis was done to compare the three treatments . A total of 50 patients , 8–19 years , participated . All treatments reduced symptoms significantly with p-values ( corrected for multiple comparisons ) of 0.0018 for each of the atypical agents and 0.012 for haloperidol . In all , 88 % of subjects treated with olanzapine , 74 % treated with risperidone , and 53 % treated with haloperidol met response criteria . The primary side effects observed in all patients were mild to moderate sedation , extrapyramidal symptoms , and weight gain . Risperidone and olanzapine acutely reduced psychotic symptoms in this pediatric sample . Exploratory comparisons indicate the magnitude of the antipsychotic response with these atypical agents is comparable to that observed with haloperidol . However , youth treated with risperidone and olanzapine experienced weight gain and extrapyramidal effects that appear more prevalent and severe than reported in adults", "BACKGROUND Childhood-onset schizophrenia is a rare but severe form of the disorder that is often treatment-refractory . In this study , the efficacy and adverse effects of clozapine and haloperidol were compared for children and adolescents with early-onset schizophrenia . METHODS Twenty-one patients ( mean [ + /-SD ] age , 14.0 + /- 2.3 years ) with onset of Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition-defined schizophrenia that began by age 12 years and who had been nonresponsive to typical neuroleptics participated in the study . Patients were r and omized to a 6-week double-blind parallel comparison of clozapine ( mean [ + /-SD ] final dose , 176 + /- 149 mg/d ) , or haloperidol , ( 16 + /- 8 mg/d ) . RESULTS Clozapine was superior to haloperidol on all measures of psychosis ( P = .04-.002 ) . Positive and negative symptoms of schizophrenia improved . However , neutropenia and seizures were major concerns . To date , one third of the group has discontinued using clozapine . CONCLUSIONS Clozapine has striking superiority for positive and negative symptoms in treatment-refractory childhood-onset schizophrenia . However , due to possibly increased toxic effects in this pediatric population , close monitoring for adverse events is essential", "The first double-blind placebo-controlled clinical trial of an atypical neuroleptic medication is being conducted in symptomatic treatment-seeking patients meeting new diagnostic criteria for a putative prodromal syndrome . This identifies them as being at high risk for developing psychosis in the near future . The study aims include prevention of psychosis onset and disability , as well as palliation of ongoing symptomatology . The purpose of this report is to describe the study 's \" prodromally symptomatic \" sample at baseline , i.e. , at intake immediately prior to r and omization and prior to receiving study medication . Sixty treatment-seeking patients meeting prodromal inclusion criteria were recruited across four sites : New Haven , CT ( n=39 ) , Toronto , Ontario ( n=9 ) , Calgary , Alberta ( n=6 ) , and Chapel Hill , NC ( n=6 ) . The sample was young ( median age 16 ) , largely male ( 65 % ) , and came from families with high titers of serious mental illness ( 44 % ) . Most patients ( 93 % ) met criteria for the Attenuated Positive Symptom ( APS ) prodromal syndrome and presented with significant but nonpsychotic suspiciousness , perceptual aberrations , unusual thought content , and conceptual disorganization . They presented with minimal to mild affective symptoms and substance use/abuse , but they were quite functionally compromised ( mean Global Assessment of Functioning ( GAF ) score=42 ) . The prodromal sample was compared with other clinical -trial sample s of adolescent depression , adolescent mania , and first episode schizophrenia . Prodromal patients proved not to be depressed or manic . They were less severely ill than untreated first episode schizophrenia but more severely ill than treated first episode schizophrenia . While not psychotically disabled , these patients nevertheless present with a clinical syndrome . Subsequent reports will detail the effects of drug versus placebo on prodromal symptoms , neuropsychological profile , and the rate of conversion to psychosis", "BACKGROUND : Childhood-onset schizophrenia is schizophrenia with onset prior to the age of 13 years . Although it is rare , people who suffer from schizophrenia at an early age appear to have a clinical ly severe form of the illness with poor long-term prognosis . Antipsychotic medication is one way of managing this rare but serious mental illness . OBJECTIVES : To examine the effects of antipsychotic medication for childhood-onset schizophrenia . SEARCH STRATEGY : We search ed the Cochrane Schizophrenia Group Trials Register ( November 2006 and February 2007 ) , inspected references of all identified studies for further trials and contacted relevant pharmaceutical companies and authors of trials for additional information . SELECTION CRITERIA : We included all r and omised clinical trials involving children and young people with a diagnosis of childhood onset schizophrenia ( i.e. with a diagnosis of schizophrenia before the age of 13 ) comparing any antipsychotic drug with another antipsychotic or placebo . DATA COLLECTION AND ANALYSIS : We reliably selected , quality assessed and extracted data from trials . We excluded data where more than 50 % of participants in any group were lost to follow up . For homogenous dichotomous data we calculated r and om effects , relative risk ( RR ) and its 95 % confidence interval ( CI ) and , where appropriate , number needed to treat ( NNT ) on an intention-to-treat basis . For normal continuous data we calculated the weighted mean difference ( WMD ) . MAIN RESULTS : From a total of 2062 citations , we identified six relevant trials . We categorised trials into three comparisons : atypical versus typical , atypical versus atypical and typical versus typical antipsychotic drugs . The only comparison to find any differences between treatment groups was atypical versus typical antipsychotic drugs . A few results from one study favoured the atypical antipsychotic clozapine over haloperidol in treating treatment resistant childhood-onset schizophrenia ( n=21 , WMD CGAS 17.00 CI 7.74 to 26.26 ; n=21 , WMD Bunney-Hamburg Psychosis Rating Scale -3.60 CI -6.64 to -0.56 ) . Participants on clozapine , however , were three times more likely to have drowsiness ( 1 RCT , n=21 , RR 3.30 CI 1.23 to 8.85 , NNH 2 CI 2 to 17 ) and half of the children receiving clozapine had neutropenia ( 1 RCT , n=21 , RR 12 , CI 0.75 to 192.86 ) . AUTHORS ' CONCLUSIONS : There are few relevant trials and , presently , there is little conclusive evidence regarding the effects of antipsychotic medication for those with early onset schizophrenia . Some benefits were identified in using the atypical antipsychotic clozapine compared with haloperidol but the benefits were offset by an increased risk of serious adverse effects . Larger , more robust , trials are required", "OBJECTIVE This study characterizes the tolerability of ziprasidone in children and adolescents with bipolar mania , schizophrenia , or schizoaffective disorder . METHOD Sixty-three subjects ( aged 10 - 17 years ) entered an open-label study consisting of a 3-week fixed-dose period ( Period 1 ) and a subsequent 24-week flexible-dose period ( Period 2 ) . In Period 1 , subjects received ziprasidone 80 or 160 mg/d in two divided doses , titrated over 10 days . In Period 2 , subjects received flexible doses ( 20 - 160 mg/d ) . Tolerability was evaluated using movement rating scales , laboratory tests , and electrocardiograms . Clinical response was assessed using the Young Mania Rating Scale , the Brief Psychiatric Rating Scale-Anchored Version , and the Clinical Global Impressions-Severity scale . RESULTS Adverse events ( AEs ) occurred mostly during dose titration and in the high-dose ( 160 mg/d ) group . The most common AEs during Period 1 were sedation ( 32 % ) , somnolence ( 30 % ) , and nausea ( 25 % ) and during Period 2 were sedation ( 30 % ) , somnolence ( 30 % ) , and headache ( 25 % ) . The incidence of movement disorder AEs was 22 % and 16 % during Periods 1 and 2 , respectively . Six percent of study participants discontinued study participation due to AEs during Period 1 and 20 % discontinued in Period 2 . Thirty-three percent of subjects gained > or=7 % of their baseline weight . No Fridericia-corrected QT ( QTcF ) intervals of > 450 ms were observed during Period 1 and only one occurred during Period 2 . No QTcF increase > or=60 ms from baseline was observed . Symptom reductions were observed in all patient groups . CONCLUSIONS No unexpected tolerability findings were observed in this prospect i ve trial of ziprasidone in children and adolescents with bipolar mania , schizophrenia , or schizoaffective disorder . On the basis of the results , a starting dose of 20 mg/d titrated to between 80 and 160 mg/d over 1 - 2 weeks appears optimal for most patients", "Quetiapine is a novel , atypical antipsychotic agent that has been shown to provide long-term efficacy without serious adverse effects in adults . This is the first study of the extended use of quetiapine in adolescents . Five boys and 5 girls , ages 12.3 to 15.9 years , with diagnoses of schizoaffective disorder ( n = 7 ) or bipolar disorder with psychotic features ( n = 3 ) were eligible for entry into this single-site , 88-week , open-label trial . Subjects had completed a pharmacokinetic study over 23 days , during which the dosage of quetiapine was increased sequentially from 25 mg bid to a maximum of 400 mg bid ( 800 mg/day ) ( McConville et al. 2000 ) . In the open-label extension of this trial , which followed directly after this trial , a physician 's choice design allowed for flexible dose titration of quetiapine by the study physician to an optimal dose for each patient , with ending doses ranging from 300 mg/day to 800 mg/day . Concomitant medications , especially for anxiety and /or manic symptoms , were allowed as deemed necessary . Tolerability and safety were assessed using clinical laboratory tests , physical examinations , measurements of vital signs , interviews for selective symptomatology , and electrocardiograms . Psychiatric measurements included the 18-item Brief Psychiatric Rating Scale ( BPRS ) , the Clinical Global Impression ( CGI ) scale , and the modified Scale for the Assessment of Negative Symptoms ( SANS ) . Neurologic symptom ratings included the Simpson-Angus Scale and the Abnormal Involuntary Movement Scale . Mean BPRS , CGI , and SANS scores improved significantly during the trial ( p extrapyramidal symptoms or evidence of tardive dyskinesia was seen . Clinical ly , there was a nonsignificant increase in mean weight and body mass index at week 64 . This long-term study suggests that quetiapine is a well-tolerated antipsychotic agent that is efficacious for the treatment of symptoms of selected psychotic disorders in adolescents", "We acquired Positron emission tomography with 18-F-deoxyglucose ( FDG-PET ) and anatomical MRI in 30 never-previously medicated psychotic adolescents ( ages 13 - 20 ) . ( FDG-PET ) was obtained at baseline and after 8 - 9 weeks of a r and omized double-blind trial of either olanzapine or haloperidol . Neuropsychological tests of executive function were also obtained . Patients carried out the serial verbal learning task , a modification of the California Verbal Learning Test , during the uptake of the FDG . PET scans were coregistered with spoiled gradient MRI ( TR=24 , TE=5 , flip angle 40 degrees , slice thickness 1.2 mm , field of view 230 mm ) for accurate anatomical identification of regions of interest traced on the MRI . Twenty-two of the thirty patients completed the second PET and clinical evaluation . Individuals treated with olanzapine increased relative metabolic rates in the frontal lobe more than the occipital lobe while patients treated with haloperidol failed to increase frontal metabolic rates and did not show an anteroposterior gradient in medication response . Haloperidol increased striatal metabolic rate more than olanzapine . Both drugs increased thalamic metabolic rates and this increase was significantly larger in younger ( age 13 - 15 ) than older ( 16 - 21 ) patients", "OBJECTIVE To review the response of 11 adolescents with childhood-onset schizophrenia to a 6-week open clozapine trial . METHOD Eleven children meeting DSM-III-R criteria for schizophrenia had a 6-week open trial of clozapine ( mean sixth week daily dose 370 mg ) . Behavioral ratings included the Brief Psychiatric Rating Scale and Children 's Global Assessment Scale . RESULTS More than half showed marked improvement in Brief Psychiatric Rating Scale ratings by 6 weeks of clozapine therapy compared to admission drug rating and compared to a systematic 6-week trial of haloperidol . CONCLUSIONS This open trial indicates that clozapine may be a promising treatment for children and adolescents with schizophrenia who do not respond well to typical neuroleptics . A double-blind placebo-controlled study is ongoing", "BACKGROUND The prodromal phase of schizophrenic disorders has been described prospect ively . The present study aim ed to determine the short-term efficacy and safety of olanzapine treatment of prodromal symptoms compared with placebo . METHODS This was a double-blind , r and omized , parallel-groups , placebo-controlled trial with fixed-flexible dosing conducted at four sites . Sixty patients met prodromal diagnostic criteria , including attenuated psychotic symptoms , as determined by structured interviews . Olanzapine 5 - 15 mg daily or placebo was prescribed for 8 weeks . RESULTS In the mixed-effects , repeated- measures analysis , the treatment x time interaction for the change from baseline on the Scale of Prodromal Symptoms total score was statistically significant , and post hoc analyses revealed that the olanzapine-placebo difference reached p Ratings of extrapyramidal symptoms remained low in each group and were not significantly different . Olanzapine patients gained 9.9 lb versus.7 lb for placebo patients ( p olanzapine is associated with significantly greater symptomatic improvement but significantly greater weight gain than is placebo in prodromal patients . Extrapyramidal symptoms with olanzapine were minimal and similar to those with placebo . Future research over the longer term with more patients will be needed before recommendations can be made regarding routine treatment", "Twenty to fifty percent of people with a diagnosis of schizophrenia continue to hear voices despite taking neuroleptic medication . Trials of group cognitive behavioral therapy for adults with auditory hallucinations have shown promising results . Auditory hallucinations may be most amenable to psychological intervention during a 3-year critical period after symptom onset . This study evaluates the effectiveness of group cognitive behavioral therapy ( CBT ) for young people with recent-onset auditory hallucinations ( N = 22 ) , using a waiting list control . Outcome measures were administered at four separate time points . Significant reductions in auditory hallucinations occurred over the total treatment phase , but not over the waiting period . Further investigations in the form of r and omized controlled trials are warranted", "A modification of an earlier rating scale for extrapyramidal system disturbance is described , and evidence for the validity and reliability of the scale is presented . The usefulness of the scale in studies of neuroleptic drugs is discussed . By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors", "BACKGROUND Plasma clozapine and haloperidol concentrations were studied in adolescents being treated for childhood-onset schizophrenia . METHOD Eleven patients ( 9 boys , 2 girls ; mean age = 14.1 + /- 2.1 years ) received a 6-week blinded or open trial of clozapine . Five patients also received 6 weeks of blinded or open haloperidol . Doses were increased on an individual basis to a mean 6-week dose of 5.99 + /- 2.6 mg/kg/day for clozapine and 0.24 + /- 0.20 mg/kg/day for haloperidol . The Brief Psychiatric Rating Scale and Bunney Hamburg Rating Scale were completed weekly for each subject . Weekly blood sample s were obtained during therapy and assayed by high performance liquid chromatography . RESULTS The mean clozapine level at Week 6 was 378.3 ng/mL and ranged from 77.5 to 1050 ng/mL. The mean Week 6 haloperidol level was 23.0 ng/mL ( range , 6.2 - 44.3 ng/mL ) . The clozapine desmethyl and N-oxide metabolites achieved mean concentrations of 77 % and 18 % , respectively , of those of the parent compound . The mean ratio of haloperidol/reduced haloperidol was 4.48 ( range , 0.76 - 8.76 ) . Clozapine concentrations versus clinical benefit exhibited a consistent linear relationship among patients ( correlation range , 0.26 - 0.96 ) . Conversely , poor and inconsistent correlations between haloperidol concentrations and clinical effects were observed . No relationships were noted between clozapine or haloperidol dose and clinical effects . CONCLUSION Adolescents with schizophrenia produce a greater amount of desmethylclozapine than previously seen in adults . Plasma clozapine concentrations appear to be related in a linear fashion to clinical improvement", "BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials", "OBJECTIVE Aripiprazole is a dopamine partial agonist approved for use in adults for short- and long-term treatment of schizophrenia and bipolar disorder . This study was design ed to examine the acute efficacy , safety , and tolerability of aripiprazole for adolescents with schizophrenia . METHOD This was a 6-week multicenter , double-blind , r and omized , placebo-controlled trial . Subjects 13 to 17 years old with a DSM-IV diagnosis of schizophrenia and a Positive and Negative Syndrome Scale ( PANSS ) total score of 70 or more were r and omly assigned ( 1:1:1 ratio ) to placebo or 10 or 30 mg/day of aripiprazole . The primary endpoint was mean change from baseline to endpoint ( last observation carried forward ) in PANSS total score . Assessment s of safety and tolerability included spontaneously reported adverse events , extrapyramidal symptom scores , serum prolactin concentration , body weight , and metabolic measures . RESULTS Of 302 patients , 85 % completed the 6-week study . The mean baseline PANSS score was 94.1 . At the end of the study , both aripiprazole doses showed statistically significant differences from placebo in reduction in PANSS total score . Adverse events occurring in more than 5 % of either aripiprazole group and with a combined incidence at least twice the rate for placebo were extrapyramidal disorder , somnolence , and tremor . Mean changes in prolactin were -8.45 , -11.93 , and -15.14 ng/ml for placebo and 10 mg and 30 mg of aripirazole , respectively . Mean body weight changes were -0.8 , 0.0 , and 0.2 kg for placebo and 10 mg and 30 mg of aripiprazole , respectively . CONCLUSION Both 10- and 30-mg/day doses of aripiprazole were superior to placebo in the acute treatment of adolescents with schizophrenia . Aripiprazole was generally well tolerated", "BACKGROUND Schizophrenia with an onset in adolescence is known to be associated with a poorer outcome and cognitive difficulties . These impairments have an impact on quality of life and represent treatment targets . Cognitive remediation therapy ( CRT ) attempts to improve cognitive deficits by teaching information processing strategies through guided mental exercises . The objective of this study is to evaluate the efficacy of CRT in alleviating cognitive deficits compared to treatment as usual and explore the mediating and moderating effects of cognitive improvement . METHOD Single-blind r and omized controlled trial with two groups , one receiving CRT ( N21 ) and the other st and ard care ( N19 ) assessed at baseline , 3 months ( post therapy ) and follow-up ( 3 months post therapy ) . Participants were recruited from specialist inpatient and community mental health services and were young patients with recent onset schizophrenia ( average age of 18 ) and evidence of cognitive and social behavioural difficulties . The intervention was individual cognitive remediation therapy delivered over a period of 3 months with at least three sessions per week . The main outcome measures were cognition ( memory , cognitive flexibility and planning ) and secondary outcomes ( symptoms , social contacts and self-esteem ) . RESULTS Compared to st and ard care , CRT produced significant additional improvements in cognitive flexibility as measured by the Wisconsin Card Sort Test ( WCST ) . Therapy moderated the effects of improved planning ability on symptoms such that improvements only had a beneficial effect when they were achieved in the context of CRT . Improvements in cognition in all domains had a direct effect on social functioning and improvements in WCST had a direct effect on overall symptom improvement . CONCLUSIONS Cognitive remediation therapy can contribute to the improvement in WCST even in adolescents . The changes in cognitive outcomes also contributed to improvements in functioning either directly or solely in the context of CRT . Evidence of the mediator and moderator effects of cognitive changes should lead to more effective therapy development", "The primary purpose of this study was to compare changes in cognition in early-onset psychosis after 6-months treatment with quetiapine or olanzapine . This is a r and omized , single-blind , 6-month study in 50 adolescents with a diagnosis of early-onset psychosis . Patients were r and omized to quetiapine ( n = 24 ) or olanzapine ( n = 26 ) . A thorough neuropsychological battery was administered at baseline and after 6-month treatment . Out of the total sample included in the study , 32 patients completed at least 6-months treatment with the assigned medication ( quetiapine , n = 16 ; olanzapine , n = 16 ) . No changes were observed in cognitive performance after 6-month treatment with quetiapine or olanzapine . Although some trends toward cognitive improvement were observed for the olanzapine group after 6-month treatment , neither group showed statistically significant gains . Furthermore , there was no evidence of any differential efficacy of olanzapine or quetiapine on cognitive improvement in this sample of adolescents with psychosis", "The objective of this study was to evaluate the efficacy and tolerability of quetiapine in the treatment of first onset psychosis in older adolescents using risperidone as a comparator . Twenty-two patients with first onset psychosis were r and omized to receive quetiapine ( up to 800 mg/day ) or risperidone ( up to 6 mg/day ) for 6 weeks . Raters blind to treatment assignment performed outcome symptom ratings . No statistical differences emerged in terms of efficacy or tolerability between the two drugs . However , there were some clinical ly notable differences that seem to favour the efficacy of risperidone over quetiapine . Patients taking quetiapine , although improved , showed less clinical improvement on scores for total positive and negative symptoms , clinical global severity and depression at 6 weeks than patients taking risperidone . Although both treatments were associated with weight gain and sedation , more patients on quetiapine experienced over 10 % weight gain . However , fewer patients who were taking quetiapine required anticholinergic medication or experienced extrapyramidal side effects than patients taking risperidone . Risperidone was significantly more likely to be associated with elevation in serum prolactin levels in this population . In conclusion , the results in this small trial show that adolescent patients may benefit more from treatment with risperidone than quetiapine . However , those susceptible to side effects , particularly hyperprolactinaemia , may be more suitable for treatment with quetiapine", "OBJECTIVE Atypical ( second-generation ) antipsychotics are considered st and ard treatment for children and adolescents with early-onset schizophrenia and schizoaffective disorder . However , the superiority of second-generation antipsychotics over first-generation antipsychotics has not been demonstrated . This study compared the efficacy and safety of two second-generation antipsychotics ( olanzapine and risperidone ) with a first-generation antipsychotic ( molindone ) in the treatment of early-onset schizophrenia and schizoaffective disorder . METHOD This double-blind multisite trial r and omly assigned pediatric patients with early-onset schizophrenia and schizoaffective disorder to treatment with either olanzapine ( 2.5 - 20 mg/day ) , risperidone ( 0.5 - 6 mg/day ) , or molindone ( 10 - 140 mg/day , plus 1 mg/day of benztropine ) for 8 weeks . The primary outcome was response to treatment , defined as a Clinical Global Impression ( CGI ) improvement score of 1 or 2 and > or=20 % reduction in Positive and Negative Syndrome Scale ( PANSS ) total score after 8 weeks of treatment . RESULTS In total , 119 youth were r and omly assigned to treatment . Of these subjects , 116 received at least one dose of treatment and thus were available for analysis . No significant differences were found among treatment groups in response rates ( molindone : 50 % ; olanzapine : 34 % ; risperidone : 46 % ) or magnitude of symptom reduction . Olanzapine and risperidone were associated with significantly greater weight gain . Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol , low density lipoprotein , insulin , and liver transaminase levels . Molindone led to more self-reports of akathisia . CONCLUSIONS Risperidone and olanzapine did not demonstrate superior efficacy over molindone for treating early-onset schizophrenia and schizoaffective disorder . Adverse effects were frequent but differed among medications . The results question the nearly exclusive use of second-generation antipsychotics to treat early-onset schizophrenia and schizoaffective disorder . The safety findings related to weight gain and metabolic problems raise important public health concerns , given the widespread use of second-generation antipsychotics in youth for nonpsychotic disorders" ]	41189ec4-06ff-11f0-808a-c43d1ab1c353
AIMS To conduct an up date d systematic review and the first meta- analysis of experimental trials investigating the acute effects of short bouts of physical activity ( PA ) on strength of desire ( SoD ) and desire to smoke ( DtS ) using individual participant data ( IPD ) . METHODS A systematic review of literature and IPD meta-analyses included trials assessing the acute effects of shorts bouts of PA on SoD and DtS among temporarily abstaining smokers not using pharmaceutical aids for smoking cessation . Authors of eligible studies were contacted and raw IPD were obtained . Two-stage and one-stage IPD r and om-effects meta-analyses were conducted . Participants engaging in PA were compared against control participants , using post-intervention SoD and DtS with baseline adjustments . RESULTS A two-stage IPD meta- analysis assessing effects of PA on SoD yielded an average st and ardized mean difference ( SMD ) between PA and control conditions ( across 15 primary studies ) of -1.91 [ 95 % confidence interval ( CI ) : -2.59 to -1.22 ] . A two-stage IPD meta- analysis assessing effects of PA on DtS yielded an average SMD between PA and control conditions ( across 17 primary studies ) of -2.03 ( 95 % CI : -2.60 to -1.46 ) . Additional meta-analyses , including those using a one-stage model , those including only parallel arm studies and meta-analyses comparing only moderate exercise against a control condition , showed significant craving reduction following PA . Despite a high degree of between- study heterogeneity , effects sizes of all primary studies were in the same direction , with PA showing a greater reduction in cravings compared with controls . CONCLUSIONS There is strong evidence that physical activity acutely reduces cigarette craving	[ "RATIONALE Attentional bias towards smoking-related cues is increased during abstinence and can predict relapse after quitting . Exercise has been found to reduce cigarette cravings and desire to smoke during temporary abstinence and attenuate increased cravings in response to smoking cues . OBJECTIVE To assess the acute effects of exercise on attentional bias to smoking-related cues during temporary abstinence from smoking . METHOD In a r and omized cross-over design , on separate days regular smokers ( n = 20 ) undertook 15 minutes of exercise ( moderate intensity stationary cycling ) or passive seating following 15 hours of nicotine abstinence . Attentional bias was measured at baseline and post-treatment . The percentage of dwell time and direction of initial fixation was assessed during the passive viewing of a series of paired smoking and neutral images using an Eyelink II eye-tracking system . Self-reported desire to smoke was recorded at baseline , mid- and post-treatment and post-eye-tracking task . RESULTS There was a significant condition x time interaction for desire to smoke , F((1,18 ) ) = 10.67 , P = 0.004 , eta(2 ) = 0.36 , with significantly lower desire to smoke at mid- and post-treatment following the exercise condition . The percentage of dwell time and direction of initial fixations towards smoking images were also reduced significantly following the exercise condition compared with the passive control . CONCLUSION Findings support previous research that acute exercise reduces desire to smoke . This is the first study to show that exercise appears to also influence the salience and attentional biases towards cigarettes", "The urges to smoke reported by 215 former smokers were measured 1 day , 7 days , 14 days and 30 days after they quit to examine : ( a ) the time course of smoking urges , ( b ) the relationship of urges to relapse , and ( c ) predictors of urges to smoke . Urges to smoke were strongest 1 day after quitting , and decreased at each subsequent measurement point . Urges were a powerful predictor of relapse . At each of the four assessment points , abstinent subjects who reported stronger urges to smoke were more likely to relapse by the next measurement point . Urges to smoke at a given day ( e.g. , day 1 ) were consistently the best predictors of the persistence of urges at the next assessment ( e.g. , day 7 ) . Greater negative emotion ( e.g. , anxiety , sadness , anger , and confusion ) and psychosocial stress also predicted stronger urges to smoke . Nicotine gum significantly reduced urges during week 1 post-cessation . Clinical implication s of the findings are discussed", "Rationale Substances of misuse ( such as nicotine ) are associated with increases in activation within the mesocorticolimbic brain system , a system thought to mediate the rewarding effects of drugs of abuse . Pharmacological treatments have been design ed to reduce cigarette cravings during temporary abstinence . Exercise has been found to be an effective tool for controlling cigarette cravings . Objective The objective of this study is to assess the effect of exercise on regional brain activation in response to smoking-related images during temporary nicotine abstinence . Method In a r and omized crossover design , regular smokers ( n = 10 ) undertook an exercise ( 10 min moderate-intensity stationary cycling ) and control ( passive seating for same duration ) session , following 15 h of nicotine abstinence . Following treatments , participants entered a functional Magnetic Resonance Imaging ( fMRI ) scanner . Subjects viewed a r and om series of smoking and neutral images for 3 s , with an average inter-stimulus-interval ( ISI ) of 10 s. Self-reported cravings were assessed at baseline , mid- , and post-treatments . Results A significant interaction effect ( time by group ) was found , with self-reported cravings lower during and following exercise . During control scanning , significant activation was recorded in areas associated with reward ( cau date nucleus ) , motivation ( orbitofrontal cortex ) and visuo-spatial attention ( parietal lobe , parahippocampal , and fusiform gyrus ) . Post-exercise scanning showed hypo-activation in these areas with a concomitant shift of activation towards areas identified in the ‘ brain default mode ’ ( Broadmanns Area 10 ) . Conclusion The study confirms previous evidence that a single session of exercise can reduce cigarette cravings , and for the first time provides evidence of a shift in regional activation in response to smoking cues", "The present study was conducted to examine the effects of acute aerobic exercise on smoking behavior . On alternate days , 10 healthy young smokers were subjected to half an hour of sustained high exercise ( about 56 % of maximum work capacity ) or of low exercise ( about 28 % of maximum , simulating normal daytime activity ) . During the high-exercise condition , there were pronounced increases in physiological markers of physical activity such as mean work , heart rate , and lactic acid as well as elevations in circulating hormones ( norepinephrine , epinephrine , and immunoreactive beta-endorphin and cortisol ) known to be affected by vigorous exercise . Despite a trend toward decreased desire for cigarettes after the high exercise condition , there were no differences in plasma nicotine levels following the smoking of a usual-br and cigarette 35 min later . The sustained effects of the two exercise conditions were also similar : plasma cotinine levels 24 hr later ( reflecting nicotine intake over the entire exercise day ) revealed no significant differences between hight and low exercise", "Rationale Smokers show heightened activation toward smoking-related stimuli and experience increased cravings which can precipitate smoking cessation relapse . Exercise can be effective for modulating cigarette cravings and attenuating reactivity to smoking cues , but the mechanism by which these effects occur remains uncertain . Objective The objective of the study was to assess the effect of exercise on regional brain activation in response to smoking-related images during temporary nicotine abstinence . Methods In a r and omised crossover design , overnight abstinent smokers ( n = 20 ) underwent an exercise ( 10-min moderate-intensity stationary cycling ) and passive control ( seating for the same duration ) treatment , following 15 h of nicotine abstinence . After each treatment , participants underwent functional magnetic resonance imaging ( fMRI ) brain scanning while viewing a r and om series of blocked smoking or neutral images . Self-reported cravings were assessed at baseline , mid- , and post-treatments . Results There was a significant interaction effect ( treatment × time ) for desire to smoke , F ( 2,32 ) = 12.5 , p exercise at all time points compared with the control treatment . After both exercise and rest , significant areas of activation were found in areas of the limbic lobe and in areas associated with visual attention in response to smoking-related stimuli . Smokers showed increased activation to smoking images in areas associated with primary and secondary visual processing following rest , but not following a session of exercise . Conclusion The study shows differing activation towards smoking images following exercise compared to a control treatment and may point to a neuro-cognitive process following exercise that mediates effects on cigarette cravings ", "Stress and exposure to smoking cues influence smoking cravings and behavior . Exercise appears to reduce cigarette cravings and withdrawal symptoms , but no study has investigated the effects of exercise on cue-elicited cravings and withdrawal symptoms , or ad libitum smoking behavior . In this study , 60 regular smokers , invited by public advertisements , were assessed at baseline following 2 hr of abstinence , and r and omized to a 15-min brisk walk or passive condition . Both groups then completed three tasks ( Stroop color-word interference task , speech task , and h and ling a lit cigarette ) . Cravings were assessed with two single items , and withdrawal symptoms were assessed using the seven-item Mood and Physical Symptoms Scale . After the laboratory session , ad libitum smoking was determined from the subject 's cell phone text message . Exercise ( mean heart rate reserve = 24 % ) attenuated increases in strength of desire to smoke , tension , poor concentration , and stress , in response to a lit cigarette , but had minimal effects on increases in cravings and withdrawal symptoms in response to the stressors . Absolute levels of cravings and withdrawal symptoms were reduced during and following exercise . Exercisers engaged in ad libitum smoking a net 57 min ( CI = 31 - 83 ) later than those in the passive condition . A 15-min brisk walk not only reduced cigarette cravings and withdrawal symptoms but also could attenuate increases in cue-elicited cravings and withdrawal symptoms , and increase the time between cigarettes smoked", "Abstract Rationale : Previous research suggests that glucose may reduce desire to smoke during periods of abstinence but a definitive test is needed . Objective : The present study aim ed to determine whether a single administration of oral glucose would reduce desire to smoke in abstaining smokers . Methods : Thirty-eight smokers attended the laboratory in the afternoon having not smoked since the previous evening . They rated their desire to smoke immediately before and at 5-min intervals for 20 min after chewing four 3-g glucose tablets ( experimental group ) or four matched placebo tablets ( control group ) . Results : Ratings of desire to smoke decreased to a greater extent in the experimental than the control group . The effect was apparent after 10 min . There was no difference between the groups in terms of feeling ” sick ” or ” satisfied ” . Conclusion : A single dose of glucose has a relatively rapid and detectable effect on desire to smoke and the effect is not mediated by feeling sick . Glucose tablets may be useful in helping to control desire to smoke during periods of abstinence", "Rationale Recent research has shown that 10 min of moderate intensity exercise reduce smoking withdrawal symptoms and desire to smoke in acutely abstinent smokers . The aim of the current study was to determine whether the reductions are related to participant expectation of these effects . Material s and methods Forty-five sedentary participants who had smoked ten or more cigarettes per day for at least 3 years reported their expectation of the effects of exercise on smoking withdrawal symptoms . Approximately 1 month later , participants were r and omly assigned to one of three groups after 11–15 h of overnight smoking abstinence . Each group read either a positive , negative or neutral statement concerning exercise effects on smoking withdrawal symptoms . They rated their expectation again and then completed 10 min of moderate intensity exercise on a stationary bicycle ergometer . Using st and ardised scales , participants rated smoking withdrawal symptoms and desire to smoke at 10 , 5 and 0 min before exercise , then at 5 and 10 min during exercise and 15 and 20 min post-exercise . Results Expectation of exercise effects on withdrawal were manipulated in the predicted directions . No significant group main effects were found for any symptom . Significant reductions in symptoms and desire to smoke occurred during and after exercise regardless of participant expectation . Conclusions Ten minutes of moderate intensity exercise can lead to reductions in desire to smoke and smoking withdrawal symptoms , which are not due to the participant ’s expectation of exercise effects . These findings support the use of short periods of exercise as an aid to smoking cessation", "AIMS To examine the acute effects of a guided relaxation routine ( body scan ) and isometric exercise on desire to smoke and tobacco withdrawal symptoms . DESIGN Experimental comparison of three conditions . PARTICIPANTS Forty-eight individuals reporting smoking > or = 10 cigarettes daily . INTERVENTION R and om assignment to one of three interventions delivered via a 10-minute audio : isometric exercise ( IE , n = 14 ) , body scanning ( BS , n = 18 ) or a reading about natural history ( control group , n = 16 ) . Interventions were delivered twice on the same day : in the laboratory , then in their ' normal ' environment . MEASUREMENTS Desire to smoke ( primary outcome ) and withdrawal symptoms were rated at pre-intervention and up to 30 minutes post-intervention . FINDINGS Controlling for baseline scores , post-intervention desire to smoke and withdrawal symptoms were significantly lower for IE and BS groups , compared with the controls , in both environments . There were no significant differences for IE versus BS . For desire to smoke , controlling for baseline values , ratings in the laboratory were significantly lower for IE and BS versus the control up to 30 minutes post-intervention . In the normal environment , these ratings were significantly lower only up to 5 minutes post-intervention . CONCLUSIONS Brief IE and BS interventions are effective for reducing desire to smoke and withdrawal symptoms in temporarily abstaining smokers . These interventions were found to be more effective in the laboratory than in the smoker 's normal environment , but this may be an artefact of there not being a sufficient ' wash-out ' period between interventions . These techniques may be beneficial for managing desire to smoke and tobacco withdrawal", "This study investigated both acute and longer term ( \" chronic \" ) effects of vigorous exercise training on affect , nicotine withdrawal , and cigarette craving among women enrolled in a smoking cessation research study . All subjects participated in a 12-week cognitive behavioral smoking cessation program and were r and omly assigned to attend three sessions per week of either a vigorous exercise program or contact control . Measures of positive and negative affect , cigarette craving , and nicotine withdrawal were administered immediately before , and again immediately after the final exercise or contact session each week of the program . Study I enrolled 24 women who had been assigned to the exercise condition . Significant reductions in negative affect , nicotine withdrawal and cigarette craving were observed following exercise most weeks of the program . No significant changes in positive affect were observed . In Study II this protocol was repeated among 62 women ( 44 exercise , 18 contact control ) in two consecutive cohorts of the larger study . Significant reduction were observed in negative affect , nicotine withdrawal and cigarette craving during most weeks of the program among exercise subjects but not contact condition subjects . No chronic ( baseline to posttreatment ) changes in positive or negative affect , cigarette craving or withdrawal symptoms were observed in either study . Vigorous exercise appears to produce acute improvements in withdrawal symptoms , cigarette craving , and negative affect among sedentary women attempting to quit smoking", "INTRODUCTION Recent studies have examined the effects of physical activity on craving to smoke and smoking withdrawal . The current study was design ed to compare and contrast the effects of 2 different forms of physical activity on general and cue-elicited craving to smoke . METHODS Following 1-hr nicotine abstinence , 76 daily smokers were r and omly assigned to engage in a 30-min bout of cardiovascular exercise ( CE ; brisk walk on a treadmill ) , Hatha yoga ( HY ) , or a nonactivity control condition . Participants completed measures of craving and mood , and a smoking cue reactivity assessment , before , immediately following , and approximately 20 min after the physical activity or control conditions . RESULTS Compared with the control condition , participants in each of the physical activity groups reported a decrease in craving to smoke , an increase in positive affect , and a decrease in negative affect . In addition , craving in response to smoking cues was specifically reduced among those who engaged in CE , whereas those who engaged in HY reported a general decrease in cravings . CONCLUSIONS This study provides further support for the use of exercise bouts for attenuating cigarette cravings during temporary nicotine abstinence . Results also suggest that CE can attenuate cravings in response to smoking cues . There are several areas for further research that may improve integration of exercise within smoking cessation treatment", "OBJECTIVE Previous studies have shown that exercise acutely reduces desire to smoke and withdrawal symptoms among adult smokers ; however , no study has examined these effects in younger smokers . This study investigated the impact of a short bout of moderate intensity exercise on desire to smoke , withdrawal symptoms and exercise-induced affect in temporarily abstinent adolescent smokers . METHODS Thirty-seven low-active male and female smokers aged 16 - 19 years , abstained from smoking overnight and were assigned to either ( i ) 10 min of moderate intensity cycle ergometry ( n=18 ) or ( ii ) a placebo control condition that involved very light intensity cycle ergometry ( n=19 ) . Measures of desire to smoke , the Mood and Physical Symptoms Scale ( MPSS ) and Subjective Exercise Experience Scale ( SEES ) were administered at baseline , 5 min during , 5 min after and 30 min after both conditions . RESULTS AND CONCLUSION A significant interaction effect for group by time was recorded for psychological distress scores , when the baseline value was covaried . Follow-up tests indicated that the exercise group reported significantly higher PD scores than the placebo control during exercise , but not at any other time point . No other significant effects were found for any other variables . Unlike research involving adult population s , a short bout of moderate intensity exercise did not alter desire to smoke among abstaining adolescent smokers and may negatively impact affective responses during exercise", "Rationale A previous study found that a 10-min bout of moderate intensity exercise reduced cigarette withdrawal symptoms and desire to smoke in sedentary smokers but the effect may have been due to participants focusing attention on physical activity rather than the activity itself . Objectives This study examined the effect of 5 min of moderate intensity exercise and 5 min of light intensity exercise on tobacco withdrawal symptoms amongst sedentary smokers . Methods Eighty-four smokers attended a laboratory session having abstained from smoking for between 11 and 14 h. Participants were r and omly allocated to one of three conditions : ( i ) light intensity exercise [ n=28 ; 10–20 % of heart rate reserve ( HRR ) ] ; ( ii ) moderate intensity exercise ( n=28 ; 40–60 % HRR ) , ( iii ) a passive control condition ( n=28 ) . Both exercise conditions involved 5 min of stationary cycling and participants rated tobacco withdrawal symptoms and cravings immediately before exercise ( baseline ) , during exercise at 2.5 min , immediately following exercise , then after 5 and 10 min of rest . Control participants made the same ratings across an equivalent time period . Results For moderate intensity exercise compared to light intensity exercise and control there was a significant reduction in strength of desire to smoke , relative to baseline , both during exercise and up to 5 min post-exercise . Relative to baseline , there were also significant reductions in restlessness , stress , tension and poor concentration at 5 and 10 min post-exercise , for moderate intensity exercise compared to light intensity exercise and control . Conclusions Five minutes of moderate intensity exercise is associated with a short-term reduction in desire to smoke and tobacco withdrawal symptoms . Very brief bouts of exercise may therefore be useful as an aid to smoking cessation ", "A brief bout of aerobic exercise ( e.g. stationary bicycle ) has been shown to result in an acute reduction in tobacco withdrawal symptoms and cravings in abstinent smokers . However , aerobic exercise is often not practical and it is of interest to examine whether non-aerobic exercise has a similar effect . We investigated whether isometric exercise ( involving muscular contractions against resistance without movement , e.g. placing the palms of the h and s together and pushing ) reduces desire to smoke and tobacco withdrawal symptoms . Following overnight abstinence smokers were r and omized to 5-min of : isometric exercises ( n = 20 ) , body scanning ( focusing attention on sensations in different areas of the body , n = 20 , control ) , or sitting passively ( n = 20 , control ) . Desire to smoke and tobacco withdrawal symptoms ( ' irritable ' , ' depressed ' , ' stressed ' , ' tense ' , ' restless ' and ' poor concentration ' ) were rated at baseline , immediately post-intervention , and 5- , 10- , 15- and 20-min post-intervention . Isometric exercise produced a significantly greater reduction in desire to smoke versus passive control at immediate post-intervention and 5-min post-intervention , relative to baseline ( p withdrawal symptoms were significantly moderated by exercise versus controls at some point between 5- to 20-min post-intervention , relative to baseline ( p Brief isometric exercise has potential for offering immediate relief from a desire to smoke", "Previous r and omized controlled trials have not supported moderate intensity exercise as an efficacious adjunct to smoking cessation treatments for women ; however , compliance with exercise programs in these studies has been poor . The purpose of this pilot study was to estimate the effects of moderate intensity exercise on smoking cessation outcomes under optimal conditions for exercise program compliance . Sixty previously sedentary , healthy , female smokers were r and omized to an 8-week program consisting of brief baseline smoking cessation counseling and the nicotine patch plus either 150 min/week of moderate intensity exercise or contact control . Participants attended a median of 86.4 % and 95.5 % of prescribed exercise/control sessions , respectively . There was a moderate , though statistically nonsignificant , effect of exercise at post-treatment for objective ly verified 7-day point prevalence abstinence ( 48.3 % vs. 23.3 % ; OR = 3.07 , 95 % CI : 0.89 - 11.07 ) and prolonged abstinence ( 34.5 % vs. 20.0 % ; OR = 2.11 , 95 % CI : 0.56 - 8.32 ) . Effects were attenuated when controlling for potential confounders , and after a 1-month , no-treatment period . The findings provide a preliminary indication that , given adequate compliance , moderate intensity exercise may enhance short-term smoking cessation outcomes for women ; however , a larger trial is warranted", "Twenty-nine cigarette smokers completed a smoking motivation question naire and had expired-air carbon monoxide ( CO ) and plasma nicotine concentrations measured prior to abstaining from smoking for 24 h. Before and after the abstinence period , the subjects rated mood and physical symptoms known to be affected by cigarette abstinence ( e.g. irritability , restlessness ) . Scores on the “ dependent smoking ” subscale of the smoking motivation question naire correlated significantly with overall withdrawal severity , craving , and increased irritability . “ Indulgent smoking ” scores correlated positively with increased hunger . Pre-abstinence plasma nicotine concentration significantly pedicted craving , hunger , restlessness , inability to concentrate and overall withdrawal severity , while expired-air CO predicted craving and restlessness only . Usual daily cigarette consumption did not significantly predict any withdrawal effects . The data indicate that pre-abstinence measures of smoking motivation and smoke intake may provide a guide to withdrawal severity on smoking cessation and that smokers with a high pre-abstinence nicotine intake experience the greatest discomfort", "Abstract . Rationale : Previous research suggests that a long bout of vigorous intensity exercise may reduce tobacco withdrawal symptoms and desire to smoke during abstinence . Objective : In the present study , we investigated whether a short bout of moderate intensity exercise reduced desire to smoke and withdrawal symptoms in abstaining smokers . Methods : Seventy-eight smokers attended the laboratory in the afternoon having not smoked since the previous evening . They rated their desire to smoke and withdrawal symptoms immediately before , during and after 10 min of moderate intensity exercise on a stationary cycle ( experimental condition ) , or after waiting passively ( control condition 1 ) or watching a video ( control condition 2 ) . Results : Ratings of desire to smoke and withdrawal symptoms decreased more in the experimental group than in both control groups , which did not differ from each other . The effect was evident at all measurement points and was maintained for at least 10 min following exercise . Conclusion : A single bout of 10 min of moderate intensity exercise has a rapid and measurable effect on desire to smoke and tobacco withdrawal symptoms in abstaining smokers . Short bouts of exercise may be useful in helping to reduce desire to smoke and withdrawal symptoms during smoking cessation", "To test the validity , magnitude , and clinical significance of the signs and symptoms of tobacco withdrawal defined by DSM-III , both observed and reported signs and symptoms were measured in 50 smokers during two days of ad lib smoking and then during the first four days of abstinence . Observer and subject ratings of the DSM-III symptoms of craving for tobacco , irritability , anxiety , difficulty concentrating , and restlessness increased after cessation . In addition , bradycardia , impatience , somatic complaints , insomnia , increased hunger , and increased eating occurred after cessation . The frequency and intensity of these symptoms varied across subjects ; however , the average distress from tobacco withdrawal was similar to that observed in psychiatric out patients . Subjects who had more withdrawal discomfort were more tolerant to the cardiovascular effects of nicotine . Subjects who had more withdrawal discomfort did not have a lower rate of smoking cessation", "AIMS AND DESIGN Moderate-intensity exercise has been shown to reduce common smoking withdrawal symptoms and desire to smoke in acutely abstinent smokers . The aim of the present study was to determine if this was caused by distraction . A secondary aim was to determine whether exercise-related changes in affect were related to a reduction in symptoms . METHODS Forty ' sedentary ' participants who had smoked at least 10 or more cigarettes per day for at least 3 years were assigned r and omly to one of two groups . They completed either 10 minutes of moderate-intensity exercise on a stationary bicycle ergometer or 10 minutes of a cognitive distraction task ( paced visual serial addition task , PVSAT ) after 11 - 15 hours of smoking abstinence . Participants rated smoking withdrawal symptoms and desire to smoke using st and ard scales at 10 , 5 and 0 minutes before the experimental intervention , then at 5 and 10 minutes after the start of the intervention and 5 and 10 minutes after its completion . FINDINGS Significant group x time interactions were observed for ratings of desire to smoke and several withdrawal symptoms ( irritability , depression , restlessness , difficulty concentrating and stress ) . There was a reduction in ratings during and immediately following exercise that was not observed with cognitive distraction . Also it was found the effects were not mediated by changes in affect observed in the exercise condition . CONCLUSIONS A brief bout of moderate-intensity exercise can lead to a rapid reduction in desire to smoke and withdrawal discomfort , which is not due to the distracting effect of exercise or the effects of mood . These findings support recommendations to smokers to use exercise as a means of helping cope with the difficulties encountered when they try to stop" ]	41189f00-06ff-11f0-808a-c43d1ab1c353
OBJECTIVE To present an evidence -based review of the perioperative management of the radical cystectomy ( RC ) patient in the context of a care re design initiative . METHODS A comprehensive review of the key factors associated with perioperative management of the RC patient was completed . PubMed , Medline , and the Cochrane data bases were queried via a computerized search . Specific topics were review ed within the scope of the three major phases of perioperative management : preoperative , intraoperative , and postoperative . Preference was given to evidence from prospect i ve r and omized trials , meta-analyses , and systematic review s. RESULTS Preoperative considerations to improve care in the RC patient should include multi-disciplinary medical optimization , patient education , and formal coordination of care . Efforts to mitigate the risk of malnutrition and reduce postoperative gastrointestinal complications may include carbohydrate loading , protein nutrition supplementation , and avoiding bowel preparation . Intraoperatively , a fluid and opioid sparing protocol may reduce fluid shifts and avoid complications from paralytic ileus . Finally , enhanced recovery protocol s including novel medications , early feeding , and multi-modal analgesia approaches are associated with earlier postoperative convalescence . CONCLUSION RC is a complex and morbid procedure that may benefit from care re design . Evidence based quality improvement is integral to this process . We hope that this review will help guide further improvement initiatives for RC	[ "Bladder cancer is the fourth most common cancer among European males . Once diagnosed with muscle invasive bladder cancer , a radical cystectomy is the first line treatment , which results in a urostomy . The placement of a urostomy and the care required impacts the patient 's life . Previous research vali date d the Urostomy Education Scale as the first st and ardized tool capable of documenting the patients ' level of stoma self-care skills and useful to guide patient education interventions . A Danish-Dutch Fellowship was established to support and provide further evidence of applicability of the Urostomy Education Scale", "PURPOSE : Colorectal surgery is associated with postoperative ileus , which contributes to delayed discharge . This study was design ed to investigate the effect of thoracic epidural anesthesia and analgesia on gastrointestinal function after colorectal surgery under st and ardized controlled postoperative care . METHODS : Forty-two patients diagnosed with either colonic cancer , diverticulitis , polyps , or adenoma , and scheduled for elective colorectal surgery , were r and omly assigned to either postoperative patient-controlled analgesia ( PCA ) with intravenous morphine ( n=21 ) or epidural analgesia with a mixture of bupivacaine and fentanyl ( n=21 ) . Postoperative early oral feeding and assistance to mobilization were offered to all patients . Pain visual analog scale ( 1–100 mm ) , passage of flatus and bowel movements , length of hospital stay , and readiness for discharge were recorded . RESULTS : Pain visual analog scale ( visual analog scale , 1–100 mm ) at rest , on coughing , and daily on mobilization was significantly lower in the epidural group compared with the patient-controlled analgesia group . Median values for the visual analog scale group were 7 ( 95 percent confidence interval , 2–18 ) mm , 19 ( 95 percent confidence interval , 4–38 ) mm , and 10 ( 95 percent confidence interval , 5–33 ) mm , respectively , and , for the patient-controlled analgesia group , were 24 ( 95 percent confidence interval , 18–51 ) mm , 59 ( 95 percent confidence interval , 33–74 ) mm , and 40 ( 95 percent confidence interval , 29–79 ) mm , respectively ( P ) . Intake of protein and calories and time out of bed were similar in both groups . Mean time intervals ± st and ard deviation from surgery to first flatus and first bowel movement occurred earlier in the epidural group , 1.9±0.6 days and 3.1±1.7 days , respectively , compared with patient-controlled analgesia , 3.6±1.5 days and 4.6 ± 1.6 days , respectively ( P occurred in 33 percent of the patient-controlled analgesia group and 28 percent of the epidural group . There was no significant difference in length of hospital stay between the two groups with a mean of 7.3±3.7 days in the patient-controlled analgesia group and 8.5±4.2 days in the epidural group . Readiness for discharge was similar in both groups . CONCLUSION : Thoracic epidural analgesia has distinct advantages over patient-controlled analgesia morphine in providing superior quality of analgesia and shortening the duration of postoperative ileus . However , discharge home was not faster , indicating that other perioperative factors influence the length of hospital stay", "BACKGROUND Radical cystectomy ( RC ) for bladder cancer is frequently associated with delayed gastrointestinal ( GI ) recovery that prolongs hospital length of stay ( LOS ) . OBJECTIVE To assess the efficacy of alvimopan to accelerate GI recovery after RC . DESIGN , SETTING , AND PARTICIPANTS We conducted a r and omized double-blind placebo-controlled trial in patients undergoing RC and receiving postoperative intravenous patient-controlled opioid analgesics . INTERVENTION Oral alvimopan 12 mg ( maximum : 15 inpatient doses ) versus placebo . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The two-component primary end point was time to upper ( first tolerance of solid food ) and lower ( first bowel movement ) GI recovery ( GI-2 ) . Time to discharge order written , postoperative LOS , postoperative ileus (POI)-related morbidity , opioid consumption , and adverse events ( AEs ) were evaluated . An independent adjudication of cardiovascular AEs was performed . RESULTS AND LIMITATIONS Patients were r and omized to alvimopan ( n=143 ) or placebo ( n=137 ) ; 277 patients were included in the modified intention-to-treat population . The alvimopan cohort experienced quicker GI-2 recovery ( 5.5 vs 6.8 d ; hazard ratio : 1.8 ; p shorter mean LOS ( 7.4 vs 10.1 d ; p=0.0051 ) , and fewer episodes of POI-related morbidity ( 8.4 % vs 29.1 % ; p incidence of opioid consumption and AEs or serious AEs ( SAEs ) was comparable except for POI , which was lower in the alvimopan group ( AEs : 7 % vs 26 % ; SAEs : 5 % vs 20 % , respectively ) . Cardiovascular AEs occurred in 8.4 % ( alvimopan ) and 15.3 % ( placebo ) of patients ( p=0.09 ) . Generalizability may be limited due to the exclusion of epidural analgesia and the inclusion of mostly high-volume centers utilizing open laparotomy . CONCLUSIONS Alvimopan is a useful addition to a st and ardized care pathway in patients undergoing RC by accelerating GI recovery and shortening LOS , with a safety profile similar to placebo . PATIENT SUMMARY This study examined the effects of alvimopan on bowel recovery in patients undergoing radical cystectomy for bladder cancer . Patients receiving alvimopan experienced quicker bowel recovery and had a shorter hospital stay compared with those who received placebo , with comparable safety . TRIAL REGISTRATION Clinical Trials.gov identifier NCT00708201", "BACKGROUND Reporting methodology is highly variable and nonst and ardized , yet surgical outcomes are utilized in clinical trial design and evaluation of healthcare provider performance . OBJECTIVE We sought to define the type , incidence , and severity of early postoperative morbidities following radical cystectomy ( RC ) using a st and ardized reporting methodology . DESIGN , SETTING , AND PARTICIPANTS Between 1995 and 2005 , 1142 consecutive RCs were entered into a prospect i ve complication data base and retrospectively review ed for accuracy . All patients underwent RC/urinary diversion by high-volume fellowship-trained urologic oncologists . MEASUREMENTS All complications within 90 d of surgery were analyzed and grade d according to the Memorial Sloan-Kettering Cancer Center complication grading system . Complications were defined and stratified into 11 specific categories . Univariate and multivariate regression models were used to define predictors of complications . RESULTS AND LIMITATIONS Sixty-four percent ( 735/1142 ) of patients experienced a complication within 90 d of surgery . Among patients experiencing a complication , 67 % experienced a complication during the operative hospital admission and 58 % following discharge . Overall , the highest grade of complication was grade 0 in 36 % ( n=407 ) , grade 1 - 2 in 51 % ( n=582 ) , and grade 3 - 5 in 13 % ( n=153 ) . Gastrointestinal complications were most common ( 29 % ) , followed by infectious complications ( 25 % ) and wound-related complications ( 15 % ) . The 30-d mortality rate was 1.5 % . CONCLUSIONS Surgical morbidity following RC is significant and , when strict reporting guidelines are incorporated , higher than previously published . Accurate reporting of postoperative complications after RC is essential for counseling patients , combined modality treatment planning , clinical trial design , and assessment of surgical success", "PURPOSE Conventional practice in colorectal surgery involves stoma education being imparted postoperatively . Proficiency in stoma management often delays patients ’ discharge following colorectal surgery . The aim of this r and omized , controlled trial was to compare preoperative intensive , community-based stoma education with conventional postoperative stoma education after elective colorectal surgery . METHODS Forty-two elective colorectal patients requiring a stoma were r and omized into an intensive preoperative teaching ( study ) or postoperative ( control ) group . Intervention for the study group included two preoperative visits in the community during which patients were taught with audiovisual aids to use and change the stoma pouching system . Goal -directed postoperative stoma education was st and ardized for both groups . Outcomes measured included time to stoma proficiency , postoperative hospital stay , unplanned stoma-related interventions in the community within six weeks of discharge , and preoperative and postoperative hospital anxiety and depression scores . Cost-effectiveness of the intervention was also evaluated . RESULTS All outcomes measured were improved in the study group , including time to stoma proficiency(5.5 vs. 9 days ; P = 0.0005 ) , hospital stay ( 8 vs. 10 days ; P = 0.029 ) , and unplanned stoma-related community interventions per patient ( median 0 vs. 0.5 ; P = 0.0309 ) . No adverse effects of the intervention were noted . The average cost saving per patient was £ 1,119 ( $ 2,104 ) for the study group compared with the control group . CONCLUSIONS Stoma education is more effective if undertaken in the preoperative setting . It results in shorter times to stoma proficiency and earlier discharge from the hospital . It also reduces stoma-related interventions in the community and has no adverse effects on patient well-being", "Abstract Objective : To evaluate the influence of preoperative abstinence on postoperative outcome in alcohol misusers with no symptoms who were drinking the equivalent of at least 60 g ethanol/day . Design : R and omised controlled trial . Setting : Copenhagen , Denmark . Subjects : 42 alcoholic patients without liver disease admitted for elective colorectal surgery . Interventions : Withdrawal from alcohol consumption for 1month before operation ( disulfiram controlled ) compared with continuous drinking . Main outcome measures : Postoperative complications requiring treatment within the first month after surgery . Perioperative immunosuppression measured by delayed type hypersensitivity ; myocardial ischaemia and arrhythmias measured by Holter tape recording ; episodes of hypoxaemia measured by pulse oximetry . Response to stress during the operation were assessed by heart rate , blood pressure , serum concentration of cortisol , and plasma concentrations of glucose , interleukin 6 , and catecholamines . Results : The intervention group developed significantly fewer postoperative complications than the continuous drinkers ( 31 % v 74 % , P=0.02 ) . Delayed type hypersensitivity responses were better in the intervention group before ( 37 mm2 v 12 mm2 , P=0.04 ) , but not after surgery ( 3 mm2 v 3 mm2 ) . Development of postoperative myocardial ischaemia ( 23 % v 85 % ) and arrhythmias ( 33 % v 86 % ) on the second postoperative day as well as nightly hypoxaemic episodes ( 4 v 18 on the second postoperative night ) occurred significantly less often in the intervention group . Surgical stress responses were lower in the intervention group ( P≤0.05 ) . Conclusions : One month of preoperative abstinence reduces postoperative morbidity in alcohol abusers . The mechanism is probably reduced pre clinical organ dysfunction and reduction of the exaggerated response to surgical stress", "BACKGROUND This study was undertaken to determine the impact of an intrathecal mixture of bupivacaine and morphine , when compared with systemic morphine , on the quality of postoperative analgesia and other outcomes in the context of the enhanced recovery after surgery ( ERAS ) programme for laparoscopic colonic resection . METHODS Fifty patients undergoing general anaesthesia were r and omly allocated to receive either a spinal mixture of bupivacaine and morphine followed by oral oxycodone ( spinal group ) or patient-controlled analgesia ( PCA group ) . The primary outcome was consumption of opioids during the first three postoperative days . Secondary outcomes were pain scores , return of bowel function and dietary intake , readiness to hospital discharge , and length of hospital stay . RESULTS Postoperative opioid consumption in the spinal group was significantly less over the first three postoperative days ( P quality of analgesia at rest in the first 24 h was better in the spinal group ( P Excessive sedation and respiratory depression were reported in two elderly patients with spinal analgesia . There were no differences between the two groups in other outcomes ( return of bowel function and dietary intake , readiness to hospital discharge , and length of hospital stay ) . CONCLUSIONS When ERAS programme is used for laparoscopic colonic resection , an intrathecal mixture of bupivacaine and morphine was associated with less postoperative opioid consumption , but has no other advantages over systemic opioids", "Background : Anesthetics and neuraxial anesthesia commonly result in vasodilation/hypotension . Norepinephrine counteracts this effect and thus allows for decreased intraoperative hydration . The authors investigated whether this approach could result in reduced postoperative complication rate . Methods : In this single-center , double-blind , r and omized , superiority trial , 166 patients undergoing radical cystectomy and urinary diversion were equally allocated to receive 1 ml·kg−1·h−1 of balanced Ringer ’s solution until the end of cystectomy and then 3 ml·kg−1·h−1 until the end of surgery combined with preemptive norepinephrine infusion at an initial rate of 2 µg·kg−1·h−1 ( low-volume group ; n = 83 ) or 6 ml·kg−1·h−1 of balanced Ringer ’s solution throughout surgery ( control group ; n = 83 ) . Primary outcome was the in-hospital complication rate . Secondary outcomes were hospitalization time , and 90-day mortality . Results : In-hospital complications occurred in 43 of 83 patients ( 52 % ) in the low-volume group and in 61 of 83 ( 73 % ) in the control group ( relative risk , 0.70 ; 95 % CI , 0.55–0.88 ; P = 0.006 ) . The rates of gastrointestinal and cardiac complications were lower in the low-volume group than in the control group ( 5 [ 6 % ] vs. 31 [ 37 % ] ; relative risk , 0.16 ; 95 % CI , 0.07–0.39 ; P 0.0003 , respectively ) . The median hospitalization time was 15 days [ range , 11 , 27d ] in the low-volume group and 17 days [ 11 , 95d ] in the control group ( P = 0.02 ) . The 90-day mortality was 0 % in the low-volume group and 4.8 % in the control group ( P = 0.12 ) . Conclusion : A restrictive-deferred hydration combined with preemptive norepinephrine infusion during radical cystectomy and urinary diversion significantly reduced the postoperative complication rate and hospitalization time ", "The aim of this trial was to compare multimodal optimization with conventional perioperative management in a consecutive series of patients undergoing a wide range of colorectal procedures", "Objective Bowel preparation ( BP ) is performed routinely before intestinal surgery to reduce the risk of postoperative infectious complications . We studied the effect of BP on patients who underwent radical cystectomy and ileal conduit surgery . Our goal was to determine whether BP in these patients provided any benefits postoperatively . Methods Between Match 2006 and January 2009 , 86 patients scheduled for radical cystectomy and ileal conduit were r and omized to preoperative BP ( group A ) or surgery without BP ( group B ) . Outcomes studied included operative time , recovery of patient and surgical complications . Results Eighty-six patients were included in the study , 47 in group A and 39 in group B. All surgeries were performed successfully using ileum . Postoperative complications were documented in 5 and 6 patients in groups A and B , respectively . Anastomotic leak occurred in 1 patient in group A , leading to multiple organ dysfunction and sepsis , with a fatal outcome . One case of ileus and three wound infections were also seen in group A. In group B , wound infection and ileus occurred in two patients each , anastomotic leak developed in 1 patient result ing to reoperation and one patient died from pulmonary embolism . No statistical difference in the frequency of complications and recovery of patient was observed between the 2 groups . Conclusions Our results suggest that no advantage is gained by preoperative BP in radical cystectomy and ileal conduit", "Introduction : Transversus abdominis plane ( TAP ) block is a new regional analgesic technique for postoperative pain in abdominal surgery . Its efficacy is not clear , and thus it needs to be explored for its regular utilisation on prolonged period . The objective was to study the continuous local anaesthetic infusion effect on postoperative analgesia . Continuous use of TAP block as an analgesic technique has not been evaluated prospect ively in clinical trials . This study evaluates the efficacy of ultrasound-guided TAP block in comparison with PCA fentanyl in major abdominal surgery . Material s and Methods : There were 20 patients in the study , allocated to TAP and control groups . The parameters measured were pain scores on a numerical rating scale ( NRS ) of 0 - 10 at various time intervals and the amount of fentanyl used as rescue analgesia . Patient satisfaction scores were recorded in the TAP block group and along with any complications related to the block . Results : The postoperative median pain scores on coughing on day one were 6.0 for control group and 2.0 for the TAP group ( P = 0.02 ) ; on day two , the equivalent scores were 7.0 and 2.0 ( P = 0.01 ) . The fentanyl requirement at one hour was 203 μ for the control group and 78 μg for the TAP group ( P = 0.03 ) ; at day one , the control and TAP requirements were 1237 μg and 664 μg respectively ( P = 0.01 ) . Three TAP patients rated their satisfaction as ‘ excellent ’ , four as ‘ satisfied , and two as ‘ poor ’ . Conclusion : TAP block is a promising technique for postoperative analgesia in major abdominal surgeries . Our study demonstrated lower pain scores in the TAP group with reduced fentanyl requirement . Further , a large scale study is needed to establish the efficacy of TAP block in this setting", "BACKGROUND Open radical cystectomy ( ORC ) is associated with substantial blood loss and a high incidence of perioperative blood transfusions . Strategies to reduce blood loss and blood transfusion are warranted . OBJECTIVE To determine whether continuous norepinephrine administration combined with intraoperative restrictive hydration with Ringer 's maleate solution can reduce blood loss and the need for blood transfusion . DESIGN , SETTING , AND PARTICIPANTS This was a double-blind , r and omised , parallel-group , single-centre trial including 166 consecutive patients undergoing ORC with urinary diversion ( UD ) . Exclusion criteria were severe hepatic or renal dysfunction , congestive heart failure , and contraindications to epidural analgesia . INTERVENTION Patients were r and omly allocated to continuous norepinephrine administration starting with 2 μg/kg per hour combined with 1 ml/kg per hour until the bladder was removed , then to 3 ml/kg per hour of Ringer 's maleate solution ( norepinephrine/low-volume group ) or 6 ml/kg per hour of Ringer 's maleate solution throughout surgery ( control group ) . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Intraoperative blood loss and the percentage of patients requiring blood transfusions perioperatively were assessed . Data were analysed using nonparametric statistical models . RESULTS AND LIMITATIONS Total median blood loss was 800 ml ( range : 300 - 1700 ) in the norepinephrine/low-volume group versus 1200 ml ( range : 400 - 2800 ) in the control group ( p red blood cells ( PRBCs ) . In the control group , 50 of 83 patients ( 60 % ) required an average of 2.9 U ( ±2.1 ) of PRBCs during hospitalisation ( relative risk : 0.54 ; 95 % confidence interval [ CI ] , 0.38 - 0.77 ; p=0.0006 ) . The absolute reduction in transfusion rate throughout hospitalisation was 28 % ( 95 % CI , 12 - 45 ) . In this study , surgery was performed by three high-volume surgeons using a st and ardised technique , so whether these significant results are reproducible in other centres needs to be shown . CONCLUSIONS Continuous norepinephrine administration combined with restrictive hydration significantly reduces intraoperative blood loss , the rate of blood transfusions , and the number of PRBC units required per patient undergoing ORC with UD", "Background Alvimopan is a peripherally acting mu-opioid receptor ( PAM-OR ) antagonist for accelerating gastrointestinal recovery after surgery . Methods Patients undergoing open laparotomy ( bowel resection , n = 418 ; hysterectomy , n = 197 ) were r and omized to receive alvimopan 6 or 12 mg or placebo orally ≥2 h before surgery and then b.i.d . until hospital discharge ( up to 7 days ) . The primary efficacy endpoint was time to gastrointestinal ( GI ) recovery ( measured by toleration of solid food and passage of flatus/stool ; GI-3 ) . Secondary endpoints included time to GI-2 recovery ( toleration of solid food and passage of stool ) and hospital discharge order written ( DCO ) . Results Alvimopan did not significantly accelerate GI-3 compared with placebo [ 6 mg : hazard ratio ( HR ) = 1.20 , p = 0.080 ; 12 mg : HR = 1.24 , p = 0.038 ) . However , after adjustment for significant covariates ( sex/surgical duration ) , benefits were significant for both doses ( 6 mg : HR = 1.24 , p = 0.037 ; 12 mg : HR = 1.26 , p = 0.028 ) . Alvimopan also significantly accelerated time to GI-2 ( 6 mg : HR = 1.37 , p = 0.008 ; 12 mg : HR = 1.33 , p = 0.018 ) and DCO ( 6 mg : HR = 1.31 , p = 0.008 ; 12 mg : HR = 1.28 , p = 0.015 ) . Adverse events were similar between groups . Conclusions Alvimopan ( 6 or 12 mg ) accelerates GI recovery and is well tolerated in patients undergoing open laparotomy", "OBJECTIVES To compare the outcome and complications of urinary diversion using ileum , with and without bowel preparation . Recent studies have question ed the necessity of bowel preparation , especially for urinary diversion when ileum is used . METHODS In this clinical trial , 30 c and i date s for urinary diversion underwent a 3-day st and ard bowel preparation ( group 1 ) , and 32 were admitted 24 hours before surgery and received only a soft diet , with no oral intake , 8 hours before surgery ( group 2 ) . They were followed up for at least 6 months and were evaluated for outcome and surgical complications . RESULTS All surgical operations were performed successfully using ileum . Postoperative complications were documented in 2 and 4 patients in groups 1 and 2 , respectively ( relative risk 0.69 , 95 % confidence interval 0.37 to 1.31 , P = 0.41 ) . Anastomotic leak , enterocutaneous fistula , and wound infection and dehiscence occurred in 1 patient in group 1 , leading to reoperation . One case of ileus was also seen in group 1 . In group 2 , wound infection and dehiscence occurred 2 in patients and ileus in 2 others . CONCLUSIONS This study failed to demonstrate any advantage of bowel preparation for urinary diversion when we use the ileal segment . Furthermore , a meticulous use of ileum can be done without the need for a colon segment in bladder substitution procedures", "PURPOSE Radical cystectomy remains associated with significant morbidity . Most series report outcomes with relatively short-term followup that may underestimate the true magnitude of the procedure and many report length of hospital stay but ignore readmission rates . We analyzed the predictors of early ( 30 days or less ) , late ( 31 to 90 days ) and cumulative 90-day hospital readmissions , as well as morbidity and mortality rates . MATERIAL S AND METHODS We review ed our prospect ively collected data base of 753 patients who underwent radical cystectomy for urothelial cancer between January 2001 and December 2007 . We examined the relationship between clinical variables and readmission rates during the early , late and 90-day postoperative period , and review ed mortality and perioperative morbidity rates . RESULTS There were 200 ( 26.6 % ) patients readmitted in the first 90 days following radical cystectomy . Of these patients 148 ( 19.7 % ) were readmitted early , 81 ( 10.8 % ) were readmitted late , and 29 ( 3.9 % ) had an early and late readmission . Logistical regression revealed gender ( OR 1.50 , 95 % CI 1.00 - 2.27 , p = 0.05 ) , age adjusted Charlson comorbidity index ( OR 1.19 , 95 % CI 1.06 - 1.34 , p = 0.003 ) and any postoperative complications before discharge home ( OR 1.84 , 95 % CI 1.19 - 2.83 , p = 0.006 ) as independent predictors of 90-day readmission . The 30 and 90-day mortality rates were 2.1 % ( 16 ) and 6.9 % ( 52 ) , respectively . CONCLUSIONS Readmission rates after radical cystectomy are significant , approaching 27 % within the first 90 days . Gender and age adjusted Charlson comorbidity index were independent predictors providing preoperative information identifying patients more likely to require readmission or possibly to benefit from a longer initial hospital stay", "BACKGROUND Low concentrations of albumin in serum and long gastric emptying times have been returned to normal in dogs by salt and water restriction , or a high protein intake . We aim ed to determine the effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection in human beings . METHODS We r and omly allocated ten patients to receive postoperative intravenous fluids in accordance present hospital practice ( > or = 3 L water and 154 mmol sodium per day ) and ten to receive a restricted intake ( water and 77 mmol sodium per day ) . All patients had no disease other than colonic cancer . The primary endpoint was solid and liquid-phase gastric emptying time , measured by dual isotope radionuclide scintigraphy on the fourth postoperative day . Secondary endpoints included time to first bowel movement and length of postoperative hospital stay . Analysis was by intention to treat . FINDINGS Median solid and liquid phase gastric emptying times ( T(50 ) ) on the fourth postoperative day were significantly longer in the st and ard group than in the restricted group ( 175 vs 72.5 min , difference 56 [ 95 % CI 12 - 132 ] , p=0.028 ; and 110 vs 73.5 min , 52 [ 9 - 95 ] , p=0.017 , respectively ) . Median passage of flatus was 1 day later ( 4 vs 3 days , 2 [ 1 - 2 ] , p=0.001 ) ; median passage of stool 2.5 days later ( 6.5 vs 4 days , 3 [ 2 - 4 ] , p=0.001 ) ; and median postoperative hospital stay 3 days longer ( 9 vs 6 days , 3 [ 1 - 8 ] , p=0.001 ) in the st and ard group than in the restricted group . One patient in the restricted group developed hypokalaemia , whereas seven patients in the st and ard group had side-effects or complications ( p=0.01 ) . INTERPRETATION Positive salt and water balance sufficient to cause a 3 kg weight gain after surgery delays return of gastrointestinal function and prolongs hospital stay in patients undergoing elective colonic resection", "Aliment Pharmacol Ther 28 , 312–325", "Thirty-two patients undergoing bowel resection were r and omized to receive either immediate postoperative nasojejunal feeding with full strength Osmolite solution for 56 hours ( n = 16 ) or routine postoperative hypocaloric fluids and gradual re introduction of diet ( n = 16 ) . Body composition changes were measured at 14 days after operation with in vivo neutron activation analysis , the wound healing response by subcutaneous implantation of Gortex tubes , and muscle function by grip strength , maximum ventilatory volume , and stimulation of the ulnar nerve at the wrist . Postoperative fatigue up to 3 months after operation was assessed using a 10-point analogue . Successful immediate enteral nutrition was established in 12 of the 16 patients . Enterally fed patients had a mean daily caloric intake of 1179 + /- 388 kcal/d ( mean + /- SD ) over the first 4 postoperative days compared with 382 + /- 71 kcal/d for the controls ( p less than 0.0001 ) . The amount of hydroxyproline accumulating in the Gortex tubes was also significantly greater ( 2.5 + /- 1.1 nmol/g tube vs 1.5 + /- 0.8 nmol/g tube ; p less than 0.02 ) . However , the amount and composition of the weight lost was not significantly different . Muscle function was not preserved , and postoperative fatigue occurred to an equal extent in both groups . Complications were similar in both groups , except for a preponderance of bowel obstructions in the controls . The time to passage of first flatus and first bowel motion , although shorter in the fed group , did not reach significance ( p = 0.07 ) . We conclude that immediate enteral nutrition is feasible and results in an improved wound healing response . ( ABSTRACT TRUNCATED AT 250 WORDS", "BACKGROUND : The transversus abdominis plane ( TAP ) block is a novel approach for blocking the abdominal wall neural afferents via the bilateral lumbar triangles of Petit . We evaluated its analgesic efficacy in patients during the first 24 postoperative hours after abdominal surgery , in a r and omized , controlled , double-blind clinical trial . METHODS : Thirty-two adults undergoing large bowel resection via a midline abdominal incision were r and omized to receive st and ard care , including patient-controlled morphine analgesia and regular nonsteroidal antiinflammatory drugs and acetaminophen ( n = 16 ) , or to undergo TAP block ( n = 16 ) in addition to st and ard care ( n = 16 ) . After induction of anesthesia , 20 mL of 0.375 % levobupivacaine was deposited into the transversus abdominis neuro-fascial plane via the bilateral lumbar triangles of Petit . Each patient was assessed by a blinded investigator in the postanesthesia care unit and at 2 , 4 , 6 , and 24 h postoperatively . RESULTS : The TAP block reduced visual analog scale pain scores ( TAP versus control , mean ± sd ) on emergence ( 1 ± 1.4 vs 6.6 ± 2.8 , P ± 1.5 , P in the first 24 postoperative hours were also reduced ( 21.9 ± 8.9 mg vs 80.4 ± 19.2 mg , P < 0.05 ) . There were no complications attributable to the TAP block . All TAP patients reported high levels of satisfaction with their postoperative analgesic regimen . CONCLUSIONS : The TAP block provided highly effective postoperative analgesia in the first 24 postoperative hours after major abdominal surgery", "PURPOSE Early recovery after surgery concepts have gained wide acceptance in various surgical specialties . However , limited data are available for radical cystectomy . A new early recovery after surgery concept was compared to a more conservative regimen in patients undergoing radical cystectomy for bladder cancer . MATERIAL S AND METHODS A total of 101 consecutive patients were prospect ively r and omized to early recovery after surgery ( 62 ) or a conservative regimen ( 39 ) ( intended r and omization ratio was 2 early recovery after surgery-to-1 conservative regimen ) . Primary end points were differences in quality of life , and secondary end points included postoperative morbidity , dem and for analgesics , time spent in the intermediate care unit , mobility and number of gastrointestinal events during hospital stay . RESULTS Quality of life parameters , as measured by the EORTC ( European Organization for the Research and Treatment of Cancer ) Quality of Life question naire QLQ-30 did not change significantly between postoperative days 3 and 7 and at discharge from hospital in the conservative regimen group , whereas a significant improvement was observed in the early recovery after surgery group . Postoperative morbidity was lower in the early recovery after surgery group in terms of wound healing disorders ( p = 0.006 ) , fever ( p = 0.004 ) and thrombosis ( p = 0.027 ) . The dem and for analgesics was significantly lower in the early recovery after surgery group . The amount of food consumed in relation to the amount of food offered was significantly higher for the early recovery after surgery group as early as day 3 ( p = 0.02 ) . Time spent in the intermediate care unit was significantly shorter for the early recovery after surgery group ( p gastrointestinal events . The main limitations of this study were the lack of long-term data as well as the single center approach . CONCLUSIONS Early recovery after surgery of patients who underwent radical cystectomy appears to have significant benefits compared to a conservative regimen in terms of postoperative morbidity , quality of life , use of analgesics and time spent in the intermediate care unit", "PURPOSE Continuous intraoperative norepinephrine infusion combined with restrictive deferred hydration improves surgical field visibility , and significantly decreases intraoperative blood loss and postoperative complications in patients undergoing radical cystectomy and urinary diversion . We determined whether the intraoperative fluid regimen would affect functional results ( continence and erectile function ) 1 year after orthotopic ileal bladder substitution . MATERIAL S AND METHODS We analyzed a subgroup of 93 patients who received an ileal orthotopic bladder substitute . The subgroup was part of a r and omized trial in 167 patients initially allocated to continuous norepinephrine administration starting with 2 μg/kg per hour combined with 1 ml/kg per hour initially and 3 ml/kg per hour crystalloid infusion after cystectomy ( norepinephrine/low volume group of 51 ) or a st and ard crystalloid infusion of 6 ml/kg per hour throughout surgery ( 42 controls ) . We prospect ively assessed daytime and nighttime continence , and erectile function 1 year postoperatively in the 93-patient subgroup . RESULTS Daytime continence was reported by 44 of 51 patients ( 86 % ) in the norepinephrine/low volume group and by 27 of 42 controls ( 64 % ) ( p = 0.016 ) , and nighttime continence was reported by 38 ( 75 % ) and 25 ( 60 % ) , respectively ( p = 0.077 ) . Erectile function recovery was reported by 26 of 33 preoperatively potent patients ( 79 % ) in the norepinephrine/low volume group and by 11 of 29 controls ( 38 % ) ( p = 0.002 ) . CONCLUSIONS Patients who undergo radical cystectomy and orthotopic bladder substitution with continuous norepinephrine infusion and restrictive hydration during surgery have significantly better daytime continence and erectile function 1 year postoperatively", "Transversus abdominis plane block is an effective postoperative analgesic technique after abdominal surgery , but no study has compared continuous transversus abdominis plane block with continuous epidural analgesia . We design ed a r and omised controlled trial comparing these techniques for major abdominal surgery . Patients in the epidural group received a bolus of 8 to 15 ml of ropivacaine 0.2 % and an infusion of 5 to 15 ml/hour and the transversus abdominis plane block group a bolus dose of 20 ml of ropivacaine 0.375 % bilaterally and an infusion of 0.2 % ropivacaine 8 ml/hour bilaterally , for three days . Both groups received paracetamol and patient controlled analgesia with fentanyl for three days . Primary outcomes were numerical rating scores for pain ( rest and dynamic over 72 hours ) and total fentanyl use ; complications and satisfaction scores were also noted . The study was terminated early after 42 patients had been r and omised ( epidural n=19 ; transversus abdominis plane block n=22 ; one excluded ) . No differences were found in regards to point pain scores or scores over time , either immediately postoperatively or in surgical wards ; total fentanyl requirement and Likert satisfaction scores were also similar in both groups . In this underpowered study we found comparable results between continuous transversus abdominis plane technique and epidural analgesia in regard to pain , analgesic use and satisfaction after abdominal surgery . To confirm this finding , r and omised trials with larger numbers of participants are needed", "Background : Meta-analyses report similar numbers needed to treat for nonsteroidal antiinflammatory drugs ( NSAIDs ) and opioids . Differences in baseline pain intensity among the studies from which these numbers needed to treat were derived may have confounded the results . NSAIDs have an opioid-sparing effect , but the importance of this effect is unclear . Therefore , the authors sought to compare the proportions of subjects who obtain pain relief with ketorolac versus morphine after surgery and to determine whether the opioid-sparing effect of an NSAID reduces the magnitude of opioid side effects . Methods : The study was a double-blind , r and omized controlled trial . The authors r and omly assigned 1,003 adult patients to receive 30 mg ketorolac or 0.1 mg/kg morphine intravenously . They calculated the proportion of subjects who achieved at least 50 % reduction in pain intensity 30 min after analgesic administration . Further , so long as pain intensity 30 min after analgesic administration was 5 or more out of 10 , patients received 2.5 mg morphine every 10 min until pain intensity was 4 or less out of 10 . The authors assessed the presence of opioid-related side effects . Results : Five hundred patients received morphine and 503 received ketorolac . Fifty percent of patients in the morphine group achieved pain relief , compared with 31 % in the ketorolac group ( difference , 19 % ; 95 % confidence interval , 13–25 % ) . The ketorolac – morphine group required less morphine ( difference , 6.5 mg ; 95 % confidence interval , −5.8 to −7.2 ) and had a lower incidence of side effects ( difference , 11 % ; 95 % confidence interval , 5–16 % ) than the morphine group . Conclusions : Opioids are more efficacious analgesics than NSAIDs , although historic data for these two drugs yield similar numbers needed to treat . Adding NSAIDs to the opioid treatment reduces morphine requirements and opioid-related side effects in the early postoperative period", "PURPOSE Poor preoperative nutritional status is a risk factor for adverse outcomes after major surgery . We evaluated the effect of preoperative nutritional deficiency on perioperative mortality and overall survival in patients undergoing radical cystectomy for bladder cancer . MATERIAL S AND METHODS A total of 538 patients underwent radical cystectomy for urothelial carcinoma between January 2000 and June 2008 , and had nutritional parameters documented . Patients with preoperative albumin less than 3.5 gm/dl , body mass index less than 18.5 kg/m(2 ) or preoperative weight loss greater than 5 % of body weight were considered to have nutritional deficiency . Primary outcomes were 90-day mortality and overall survival . Survival was estimated using Kaplan-Meier analysis and compared using the log rank test . Cox proportional hazards models were used for multivariate survival analysis . RESULTS Of 538 patients 103 ( 19 % ) met the criteria for nutritional deficiency . The 90-day mortality rate was 7.3 % overall ( 39 deaths ) , with 16.5 % in patients with nutritional deficiency and 5.1 % in the others ( p Nutritional deficiency was a strong predictor of death within 90 days on multivariate analysis ( HR 2.91 ; 95 % CI 1.36 , 6.23 ; p Overall survival at 3 years was 44.5 % ( 33.5 , 54.9 ) for nutritionally deficient patients and 67.6 % ( 62.4 , 72.2 ) for those who were nutritionally normal ( p of all cause mortality ( HR 1.82 ; 95 % CI 1.25 , 2.65 ; p preoperative weight loss , body mass index and serum albumin , is a strong predictor of 90-day mortality and poor overall survival . Prospect i ve studies are needed to demonstrate the best indices of preoperative nutritional status and whether nutritional intervention can alter the poor prognosis for patients treated with radical cystectomy who have nutritional deficiencies ", "Perioperative hypothermia can have a wide range of underappreciated , detrimental effects . These include increased rates of wound infection , morbid cardiac events , blood loss , and length of stay in both recovery and hospital . Maintaining core temperature at or above 36 ° C can be beneficial for the patient and cost effective . Frank et al studied high risk cardiac patients undergoing thoracic , abdominal , and vascular surgery.1 Patients r and omised to routine thermal care were , on average , 1.3 ° C cooler than patients warmed more aggressively . Despite this small difference the incidence of perioperative morbid cardiac events , assessed in a double blind fashion , was 300 % higher in the cooler group . Frank et al thought that this may be the a consequence of the dramatic increase in noradrenaline release seen in even mild hypothermia . It has also been said that the increase in noradrenaline may contribute to the higher number of wound infections seen in hypothermic patients . A r and omised study of patients undergoing colorectal surgery showed that 1.9 ° C hypothermia result ed in an infection rate of 19 % compared with 6 % in the normothermic ", "Summary of Studies on Inﬂuence of Preoperative Teaching on Postoperative Outcomes Study Methods Outcomes Haugen , Bliss , & Savik 17 Chaudhri et al 18 Gulbiniene et al 19 Abbreviations : RCT , R and omized Clinical Trial ; HRQoL , Health Related Quality of Life . Cross-sectional survey of community-dwellingpersons with an incontinent ostomy RCT , compared traditional preoperativeeducation to intensive teaching interventionusing community-based nurses with expertisein colorectal and ostomy nursingCompared control group to group receivingpreoperative education and stoma sitemarking ; method of group assignment notspeciﬁed in English- language abstract Preoperative education by WOC nurse associatedwith improved long-term adjustment to livingwith an ostomyIntensive , community-based education reduced the time to pouching efﬁciency , length ofpostoperative hospital stay , and unplannedostomy-related interventions when compared totraditional preoperative educationPreoperative teaching alone did not improveHRQoL , but preoperative teaching combined withstoma site marking by a stoma therapist didimprove postoperative", "BACKGROUND Despite recent improvements , radical cystectomy ( RC ) is still associated with adverse rates for 90-d mortality . OBJECTIVE To vali date the performance of the Isbarn nomogram incorporating age and postoperative tumor characteristics for predicting 90-d RC mortality in a multicenter series and to generate a new nomogram based strictly on preoperative parameters . DESIGN , SETTING , AND PARTICIPANTS Data of 679 bladder cancer ( BCa ) patients treated with RC at 18 institutions in 2011 were prospect ively collected , from which 597 patients were eligible for final analysis . INTERVENTION RC for BCa . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS An established prediction tool , the Isbarn nomogram , was applied to our cohort . For the purpose of external validation , model discrimination was measured using the receiver operating characteristics-derived area under the curve . Calibration plots examined the relationship between predicted and observed probabilities . Univariable and multivariable logistic regression models were fitted to assess the impact of preoperative characteristics on 90-d mortality . RESULTS AND LIMITATIONS The 30- , 60- , and 90-d mortality rates in the development cohort ( n=597 ) were 2.7 % , 6.7 % , and 9.0 % , respectively . The Isbarn nomogram predicted individual 90-d mortality with an accuracy of 68.6 % . Our preoperative multivariable model identified age ( odds ratio [OR]:1.052 ) , American Society of Anesthesiologists score ( OR : 2.274 ) , hospital volume ( OR : 0.982 ) , clinical ly lymphatic metastases ( OR : 4.111 ) , and clinical ly distant metastases ( OR : 7.788 ) ( all p 90-d mortality ( predictive accuracy : 78.8 % ) . Our conclusions are limited by the lack of an external validation of the preoperative model . CONCLUSIONS The Isbarn nomogram was vali date d with moderate discrimination . Our newly developed model consisting of preoperative characteristics might outperform existing models . Our model might be particularly suitable for preoperative patient counseling . PATIENT SUMMARY The current report vali date d an established nomogram predicting 90-d mortality in patients with bladder cancer after radical cystectomy ( RC ) . We developed a new prediction tool consisting of strictly preoperative parameters , thus allowing clinicians an optimal consultation for RC c and i date", "Subcostal transversus abdominis plane ( TAP ) catheters have been reported to be an effective method of providing analgesia after upper abdominal surgery . We compared their analgesic efficacy with that of epidural analgesia after major upper abdominal surgery in a r and omised controlled trial . Adult patients undergoing elective open hepatobiliary or renal surgery were r and omly allocated to receive subcostal TAP catheters ( n = 29 ) or epidural analgesia ( n = 33 ) , in addition to a st and ard postoperative analgesic regimen comprising of regular paracetamol and tramadol as required . The TAP group patients received bilateral subcostal TAP catheters and 1 mg.kg−1 bupivacaine 0.375 % bilaterally every 8 h. The epidural group patients received an infusion of bupivacaine 0.125 % with fentanyl 2 μg.ml−1 . The primary outcome measure was visual analogue pain scores during coughing at 8 , 24 , 48 and 72 h after surgery . We found no significant differences in median ( IQR [ range ] ) visual analogue scores during coughing at 8 h between the TAP group ( 4.0 ( 2.3–6.0 [ 0–7.5 ] ) ) and epidural group ( 4.0 ( 2.5–5.3 ) [ 0–8.5 ] ) ) and at 72 h ( 2.0 ( 0.8–4.0 [ 0–5 ] ) and 2.5 ( 1.0–5.0 [ 0–6 ] ) , respectively ) . Tramadol consumption was significantly greater in the TAP group ( p = 0.002 ) . Subcostal TAP catheter boluses may be an effective alternative to epidural infusions for providing postoperative analgesia after upper abdominal surgery", "INTRODUCTION The utility of a preoperative mechanical bowel preparation prior to bowel surgery has recently been question ed . The purpose of this study is to compare the perioperative outcomes between patients undergoing cystectomy with urinary diversion with or without preoperative mechanical bowel preparation . METHODS Seventy patients underwent radical cystectomy and urinary diversion between May 2008 and August 2009 for bladder cancer . The first cohort of patients ( n = 37 ) underwent cystectomy and diversion during the period May 2008-December 2008 and underwent a preoperative mechanical bowel preparation including a clear liquid diet , magnesium citrate solution , and an enema before surgery . The second cohort of patients underwent surgery during the period of January 2009-August 2009 ( n=33 ) . These patients were given a regular diet before surgery and did not undergo a mechanical bowel preparation except for the enema before surgery was performed to decrease rectal/colonic distention . Outcome measures included gastrointestinal and overall complications , and perioperative outcomes including recovery of bowel function . RESULTS There were no differences with regard to recovery of bowel function , time to discharge , or overall complication rates between the 2 groups . More specifically , the rate of GI complications was not different in prepped patients vs. nonprepped patients ( 22 % vs. 15 % ; P = 0.494 ) . There were no occurrences of bowel anastomotic leak , fistula , abscess , peritonitis , or surgical site infection in either group . One perioperative death occurred in the nonprepped group secondary to cardiovascular complications . CONCLUSIONS Preoperative mechanical bowel preparation prior to radical cystectomy with urinary diversion does not demonstrate any significant advantage in perioperative outcomes , including gastrointestinal complications . Further studies aim ed at measuring patient satisfaction and larger r and omized trials will be beneficial in evaluating the role of mechanical bowel preparation prior to urinary diversion", "PURPOSE Postoperative ileus presents significant clinical challenges that potentially prolong hospital stay , contribute to readmission , and increase morbidity . There is no approved treatment for postoperative ileus . Alvimopan is a novel , peripherally acting , mu opioid receptor antagonist currently in development for the management of postoperative ileus . METHODS Patients undergoing partial colectomy or simple or radical hysterectomy were r and omized to receive alvimopan 6 mg ( n = 152 ) , alvimopan 12 mg ( n = 146 ) , or placebo ( n = 153 ) orally 2 hours before surgery and twice daily thereafter until discharge or for up to seven days . The primary efficacy end point , time to return of gastrointestinal function , was a composite measure of passage of flatus or stool and tolerating solid food . Secondary end points included time to the hospital discharge order written . Adverse events were monitored throughout the study . RESULTS Mean time to gastrointestinal recovery was significantly reduced in patients treated with alvimopan 6 mg vs. placebo ( hazard ratio = 1.45 ; P = 0.003 ) , with a smaller reduction seen with alvimopan 12 mg ( hazard ratio = 1.28 ; P = 0.059 ) . Mean time to the hospital discharge order written was significantly accelerated in patients treated with alvimopan 6 mg ( hazard ratio = 1.50 ; P nausea , vomiting , and hypotension ; the incidence of nausea and vomiting was reduced by 53 percent in the alvimopan 12-mg group . CONCLUSIONS In patients undergoing major abdominal surgery , alvimopan accelerated gastrointestinal recovery and time to the hospital discharge order written compared with placebo and was well tolerated", "OBJECTIVES To determine whether chewing gum during the postoperative period facilitates the recovery of bowel function and has different efficacy according to operative method used in patients with radical cystectomy . METHODS From July 2007 to September 2009 , we r and omized open radical cystectomy ( ORC ) patients into Group AI ( ORC without gum chewing ) and Group AII ( ORC with gum chewing ) . Robot-assisted radical cystectomy ( RARC ) patients were r and omized into Group BI ( RARC without gum chewing ) and Group BII ( RARC with gum chewing ) . RESULTS A total of 32 ORC ( 17 Group AI and 15 Group AII ) and 28 RARC ( 13 Group BI and 15 Group BII ) patients were completed . The patient 's perioperative data between the control ( AI + BI ) and chewing gum ( AII + BII ) group showed no differences . The median time to flatus and to bowel movement were significantly reduced in chewing gum group compared with the control patients : 57.1 vs. 69.5 hours 76.7 vs. 93.3 hours . In the ORC patients , decrease in time to flatus and bowel movement were observed in gum chewing ( AII ) group than control ( AI ) group : 64.3 vs. 80.3 hours 83.8 vs. 104.2 hours . In RARC patients , decrease in time to flatus and bowel movement were found in gum chewing ( BII ) group than control ( BI ) group : 48.8 vs. 60.3 hours 69.1 vs. 84.6 hours . No adverse effects were observed with chewing gum . CONCLUSIONS Chewing gum had stimulatory effects on bowel motility after cystectomy and urinary diversion . Chewing gum was safe and could be used for postoperative ileus regardless of the operative method ( ORC or RARC )", "PURPOSE Orthotopic neobladder reconstruction is the preferred method of urinary diversion after radical cystoprostatectomy . We evaluated urinary functional outcomes in male patients after orthotopic neobladder using a patient question naire . MATERIAL S AND METHODS Between 2002 and 2009 patients with bladder cancer were enrolled in a clinical trial , r and omly assigned to undergo T pouch or Studer pouch diversion after radical cystoprostatectomy . Male patients were mailed a question naire 12 or more months after surgery including items on urinary function , intermittent catheterization , number/size/wetness of pads and mucus leakage . RESULTS The question naire response rate was 68 % . Mean followup was 4.5 years ( range 1 to 8) . Only 22.3 % of patients did not use pads . In the daytime 47 % of patients used at least 1 pad , 32.2 % used small/mini pads and 22.6 % used diapers . At night 72 % used pads , 14.7 % used small/mini pads and 38.9 % used diapers . During the day and night 47 % said their pads were dry/barely wet . Overall 62.5 % of patients reported mucus leakage . Only 9.5 % of patients performed clean intermittent self-catheterization , of whom 70.6 % started clean intermittent self-catheterization within the first year after surgery . Increasing age and diabetes mellitus were predictors of urinary function ( p = 0.005 and 0.03 , respectively ) but did not affect pad use . CONCLUSIONS Ileal orthotopic neobladder offers good functional results but most patients wear at least 1 pad and many require diapers at night . Increasing age and diabetes mellitus predict worse urinary function but are not associated with pad use . Emptying failure is uncommon and occurs early in the postoperative period . Pad size/wetness and mucus leakage should be considered when evaluating urinary incontinence", "Background This review aims to present a consensus for optimal perioperative care in colonic surgery and to provide grade d recommendations for items for an evidence d-based enhanced perioperative protocol . Methods Studies were selected with particular attention paid to meta-analyses , r and omised controlled trials and large prospect i ve cohorts . For each item of the perioperative treatment pathway , available English- language literature was examined , review ed and grade d. A consensus recommendation was reached after critical appraisal of the literature by the group . Results For most of the protocol items , recommendations are based on good- quality trials or meta-analyses of good- quality trials ( quality of evidence and recommendations according to the GRADE system ) . Conclusions Based on the evidence available for each item of the multimodal perioperative care pathway , the Enhanced Recovery After Surgery ( ERAS ) Society , International Association for Surgical Metabolism and Nutrition ( IASMEN ) and European Society for Clinical Nutrition and Metabolism ( ESPEN ) present a comprehensive evidence -based consensus review of perioperative care for colonic surgery", "BACKGROUND After radical cystectomy , patients are in a catabolic state because of postoperative stress response , extensive wound healing , and ileus . OBJECTIVE To evaluate whether recovery can be improved with total parenteral nutrition ( TPN ) in patients following extended pelvic lymph node dissection ( ePLND ) , cystectomy , and urinary diversion ( UD ) . DESIGN , SETTING , AND PARTICIPANTS We conducted a prospect i ve , r and omised , single-centre study of 157 consecutive cystectomy patients . INTERVENTION Seventy-four patients ( group A ) received TPN during the first 5 postoperative days , with additional oral intake ad libitum . Eighty-three patients ( group B ) received oral nutrition alone . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcome was the occurrence of postoperative complications . Secondary outcomes were time to recovery of bowel function , biochemical nutritional ( serum albumin , serum prealbumin , serum total protein ) and inflammatory ( C-reactive protein ) parameters , length of hospital stay , and costs attributed to the TPN . The Pearson χ(2 ) test was used for dichotomous variables ; the Wilcoxon rank sum test was used for continuous variables . RESULTS AND LIMITATIONS Postoperative complications occurred in 51 patients ( 69 % ) in group A and in 41 patients ( 49 % ) in group B ( p=0.013 ) , a difference result ing from group A having more infectious complications than group B ( 32 % vs 11 % ; p=0.001 ) . Serum prealbumin and serum total protein were significantly lower in group B on postoperative day 7 but not on postoperative day 12 . Time to gastrointestinal recovery and length of hospital stay did not differ between the two groups . The costs for TPN were € 614 per patient . A potential limitation is the use of a glucose-based parenteral nutrition without lipids . CONCLUSIONS Postoperative TPN is associated with a higher incidence of complications , mainly infections , and higher costs following ePLND , cystectomy , and UD versus oral nutrition alone" ]	41189f3c-06ff-11f0-808a-c43d1ab1c353
Background Physical fitness is a powerful health marker in childhood and adolescence , and it is reasonable to think that it might be just as important in younger children , i.e. preschoolers . At the moment , research ers , clinicians and sport practitioners do not have enough information about which fitness tests are more reliable , valid and informative from the health point of view to be implemented in preschool children . Objective Our aim was to systematic ally review the studies conducted in preschool children using field-based fitness tests , and examine their ( 1 ) reliability , ( 2 ) validity , and ( 3 ) relationship with health outcomes . Our ultimate goal was to propose a field-based physical fitness-test battery to be used in preschool children . Data Sources PubMed and Web of Science . Study Eligibility Criteria Studies conducted in healthy preschool children that included field-based fitness tests . Study Appraisal and Synthesis Methods When using PubMed , we included Medical Subject Heading ( MeSH ) terms to enhance the power of the search . A set of fitness-related terms were combined with ‘ child , preschool ’ [ MeSH ] . The same strategy and terms were used for Web of Science ( except for the MeSH option ) . Since no previous review s with a similar aim were identified , we search ed for all articles published up to 1 April 2014 ( no starting date ) . A total of 2,109 articles were identified , of which 22 articles were finally selected for this review . Results Most studies focused on reliability of the fitness tests ( n = 21 , 96 % ) , while very few focused on validity ( 0 criterion-related validity and 4 ( 18 % ) convergent validity ) or relationship with health outcomes ( 0 longitudinal and 1 ( 5 % ) cross-sectional study ) . Motor fitness , particularly balance , was the most studied fitness component , while cardiorespiratory fitness was the least studied . After analyzing the information retrieved in the current systematic review about fitness testing in preschool children , we propose the PREFIT battery , field-based FITness testing in PREschool children . The PREFIT battery is composed of the following tests : the 20 m shuttle-run test for assessing cardiorespiratory fitness , the h and grip-strength and the st and ing long-jump tests for assessing musculoskeletal fitness , and the 4 × 10 m shuttle run and the one-leg-stance tests for assessing motor fitness , i.e. speed/agility and balance , respectively . The rationale for the selection of each of the tests included in the PREFIT battery is provided in this review , as well as directions for future research . Limitations Levels of evidence based on quality assessment of selected studies could not be constructed due to the limited number of studies identified for each test . Conclusions The present systematic review has identified a need for further research on the validity of fitness tests in preschool children , as well as on their relationship with health . Due to this limited information , the PREFIT battery hereby proposed is based on the output of the current systematic review in preschool children , together with existing evidence in older children and adolescents . While we wait for more evidence to be accumulated in preschool children , the PREFIT battery hereby proposed is a useful tool for assessing physical fitness in children aged 3–5 years	[ "OBJECTIVE To prospect ively examine the effects of a r and omized school-based intervention on nutrition and physical activity knowledge and preferences , anthropometric measures , and fitness in low socioeconomic kindergarten children . STUDY DESIGN A total of 376 children completed a school-year combined dietary-behavioral-physical activity intervention and were compared with 349 control subjects ( age 3.8 to 6.8 years ) . RESULTS The prevalence of overweight and obesity among the kindergarten children was 27.7 % . Even though the intervention was not associated with between group differences in body mass index changes , it was associated with significantly ( P nutrition knowledge and preferences , physical activity knowledge and preferences , and improvement in fitness . There was a greater ( P number of overweight children in the intervention group ( -31.9 % ) compared with the controls ( -17.5 % ) . CONCLUSIONS A kindergarten dietary-physical activity intervention applied by the kindergarten teachers , had no effect on body mass index changes between the groups , but improved nutrition and physical activity knowledge and preferences , improved fitness , and decreased the percent of overweight children . This intervention may play an important role in health promotion , prevention and treatment of childhood obesity", "Objective To test the effect of a multidimensional lifestyle intervention on aerobic fitness and adiposity in predominantly migrant preschool children . Design Cluster r and omised controlled single blinded trial ( Ballabeina study ) over one school year ; r and omisation was performed after stratification for linguistic region . Setting 40 preschool classes in areas with a high migrant population in the German and French speaking regions of Switzerl and . Participants 652 of the 727 preschool children had informed consent and were present for baseline measures ( mean age 5.1 years ( SD 0.7 ) , 72 % migrants of multicultural origins ) . No children withdrew , but 26 moved away . Intervention The multidimensional culturally tailored lifestyle intervention included a physical activity programme , lessons on nutrition , media use ( use of television and computers ) , and sleep and adaptation of the built environment of the preschool class . It lasted from August 2008 to June 2009 . Main outcome measures Primary outcomes were aerobic fitness ( 20 m shuttle run test ) and body mass index ( BMI ) . Secondary outcomes included motor agility , balance , percentage body fat , waist circumference , physical activity , eating habits , media use , sleep , psychological health , and cognitive abilities . Results Compared with controls , children in the intervention group had an increase in aerobic fitness at the end of the intervention ( adjusted mean difference : 0.32 stages ( 95 % confidence interval 0.07 to 0.57 ; P=0.01 ) but no difference in BMI ( −0.07 kg/m2 , −0.19 to 0.06 ; P=0.31 ) . Relative to controls , children in the intervention group had beneficial effects in motor agility ( −0.54 s , −0.90 to −0.17 ; P=0.004 ) , percentage body fat ( −1.1 % , −2.0 to −0.2 ; P=0.02 ) , and waist circumference ( −1.0 cm , −1.6 to −0.4 ; P=0.001 ) . There were also significant benefits in the intervention group in reported physical activity , media use , and eating habits , but not in the remaining secondary outcomes . Conclusions A multidimensional intervention increased aerobic fitness and reduced body fat but not BMI in predominantly migrant preschool children . Trial registration Clinical Trials NCT00674544", "PURPOSE To determine if there is an optimal grip span for determining the maximum h and grip strength in male and female teenagers , and if the optimal grip span was related to h and span . If they are related then the second aim was to derive a mathematic equation relating h and span and optimal grip span . METHODS One hundred healthy teenage boys ( 15.1 + /- 1.1 y ) and 106 girls ( 15.4 + /- 1.3 y ) were evaluated ( age range , 13 - 18 y ) . Each h and was r and omly tested on 10 occasions using 5 different grip spans , allowing a 1-minute rest between attempts . The h and span was measured from the tip of the thumb to the tip of the small finger with the h and opened as wide as possible . RESULTS The results showed that an optimal grip span to determine the maximum h and grip strength was identified for both genders , and the optimal grip span and h and span correlated in both genders . CONCLUSIONS The results suggest that there is an optimal grip span to which the dynamometer should be adjusted when measuring h and grip strength in teenagers . The optimal grip span was influenced by h and span in both genders . For males the optimal grip span can be derived from the equation y = x/7.2 + 3.1 cm , and for females from the equation y = x/4 + 1.1 cm . where y is the optimal grip span and x is the h and -span . These equations may improve the reliability and accuracy of the results and may guide clinicians and research ers in selecting the optimal grip span on the h and dynamometer when measuring h and grip strength in teenagers", "PURPOSE Information about factors related to overweight development in early stages of life is needed for design ing useful strategies to prevent overweight and related diseases . Longitudinal studies can contribute to this goal . The present study aim ed to identify factors in childhood that determine the development of overweight/obesity in adolescence . METHODS A prospect i ve study in 598 normal-weight Estonian and Swedish children age 9.5 ± 0.4 yr from the European Youth Heart Study , who were followed during 6 yr , was conducted . Weight and height were measured at baseline and follow-up , and weight status was ascertained according to the international criteria for body mass index . Cardiorespiratory fitness ( expressed as VO(2max ) ( mL·kg(-1)·min(-1 ) ) ) was assessed by a maximal bike test . Parents reported their weight , height , and educational level . RESULTS Being male ( vs female ) and Estonian ( vs Swedish ) was related to higher risk for incident overweight/obesity . Change in fitness was a stronger predictor of incident overweight/obesity than childhood fitness , parental overweight , or parental education . The risk of developing overweight/obesity was reduced 10 % every 1 mL·kg(-1)·min(-1 ) of VO(2max ) increase ( odds ratio = 0.90 and 95 % confidence interval = 0.84 - 0.95 ) after adjustment for a set of confounders including baseline body mass index and without differences by gender . CONCLUSIONS Our results suggest that improvements in fitness from childhood to adolescence are associated with a lower risk of becoming overweight/obese in adolescence . The current findings highlight the importance of promoting fitness through physical exercise from early stages in life , as a promising strategy to fight against overweight and obesity . Gender and country differences observed in this study require social and political attention", "To assess influence of age , sex , and lateral dominance on children 's unilateral stance , from 6 Houston area preschools and day-care centers , 121 subjects were r and omly selected and judged by teachers as normal 3- to 6-yr.-old children . The children were tested for eye , h and , and foot preference and were then classified on over-all dominance . Maximal duration of unilateral stance , or up to 60 sec. , was tested on each foot . Means over age groups show progressive increase in duration of unilateral stance with increasing age . No sex differences were found . A stepwise multiple correlation-regression showed stance on the nondominant foot and age as the only significant variables in stance on the dominant foot . Clinical ly , this study can help in evaluating children for neurodevelopmental disorders", "Objective : This study assesses differences in adiposity , aerobic fitness , and lifestyle characteristics in preschoolers according to their weight status and sports club ( SC ) participation . Method : As part of the Ballabeina study , 600 r and omly selected preschoolers ( mean age 5.1 ± 0.6 years ; 50.2 % girls ) were analyzed . Body composition was measured by bioelectrical impedance , aerobic fitness by the 20-meter shuttle run test , and physical activity by accelerometers . Eating habits , media use , and SC participation were assessed by question naires . Results : Overweight children ( Swiss national percentiles ) and children not participating in SC had both lower aerobic fitness and higher % body fat compared to their respective counterparts ( all p ≤ 0.028 ) . In addition , children not participating in SC were less physically active , had more media use , and ate less healthy compared to children participating in SC ( all p ≤ 0.023 ) . Controlling for parental sociocultural determinants attenuated differences in % body fat , in physical activity , and in eating habits . Conclusion : Aerobic fitness differs both according to weight status and SC participation in preschoolers . Furthermore , in view of the many differences in lifestyle behaviors , SC participation at this age could represent a more discriminatory indicator of healthy lifestyle characteristics than weight status", "The aim of this paper was to examine the validity and reliability of age b and 1 of the Movement Assessment Battery for Children-Second Edition ( MABC-2 ) in preparation for its st and ardization in mainl and China . Interrater and test-retest reliability of the MABC-2 was estimated using Intraclass Correlation Coefficient ( ICC ) . Cronbach 's alpha for each item and Item-total correlation were used to determine internal consistency . The content validity was determined by the Item-level content validity index ( I-CVI ) . Confirmatory factor analysis was used to examine the factorial validity of the MABC-2 test . The correlation coefficients between the MABC-2 and the Peabody Developmental Motor Scales-2 ( PDMS-2 ) were used to assess the criteria -related validity . The Cronbach 's alpha values of all eight items together were moderate but acceptable . The correlation coefficients between each test item and the total score were moderate except for two items . The ICC of interrater and test-retest reliability for each test items was good . The I-CVI of each item was excellent ( each above 0.78 ) . The result of confirmatory factor analysis showed that the goodness-of-fit indices of the adjusted model were good ( each above 0.9 ) , indicating a satisfactory fit of the data to the model . The total score on MABC-2 and PDMS-2 was correlated well ( r=0.631 ) . It is concluded that the reliability and validity of age b and 1 of MABC-2 were fair in this study based on a large sample . However , there was a need to adjust part of items to improve the test 's psychometric properties when it is used in Chinese children", "The purpose of this study was to determine test-retest reliability for the 1-mile , 3/4-mile , and 1/2-mile distance run/alk tests for children in Grade s K-4 . Fifty-one intact physical education classes were r and omly assigned to one of the three distance run conditions . A total of 1,229 ( 621 boys , 608 girls ) completed the test-retests in the fall ( October ) , with 1,050 of these students ( 543 boys , 507 girls ) repeating the tests in the spring ( May ) . Results indicated that the 1-mile run/walk distance , as recommended for young children in most national test batteries , has acceptable intraclass reliability ( .83 less than R less than .90 ) for both boys and girls in Grade s 3 and 4 , has minimal ( fall ) to acceptable ( spring ) reliability for Grade 2 students ( .70 less than R less than .83 ) , but is not reliable for children in Grade s K and 1 ( .34 less than R less than .56 ) . The 1/2 mile was the only distance meeting minimal reliability st and ards for boys and girls in Grade s K and 1 ( .73 less than R less than .82 ) . Results also indicated that reliability estimates remained fairly stable across gender and age groups from the fall to spring testing periods , with the exception of the noticeably improved values for Grade 2 students on the 1-mile run/walk test . Criterion-referenced reliability ( P , percent agreement ) was also estimated relative to Physical Best and Fitnessgram run/walk st and ards . Reliability coefficients for all age group st and ards were acceptable to high ( .70 less than P less than .95 ) , except for Fitnessgram st and ards for 5-year-old girls on the 1-mile test for both fall and spring and for 6-year-old boys and girls on the 1-mile test administered in the spring", "Vicente-Rodríguez , G , Rey-López , JP , Ruíz , JR , Jiménez-Pavón , D , Bergman , P , Ciarapica , D , Heredia , JM , Molnar , D , Gutierrez , A , Moreno , LA , and Ortega , FB . Interrater reliability and time measurement validity of speed-agility field tests in adolescents . J Strength Cond Res 25(7 ) : 2059 - 2063 , 2011—The aim of this study was to examine the interrater reliability ( trained vs. untrained raters ) and criterion-related validity ( manual vs. automatic timing ) of the 4 × 10-m shuttle run and 30-m running speed tests ( times measured ) . The study comprised 85 adolescents ( 38 girls ) aged 13.0 - 16.9 years from the Healthy Lifestyle in Europe by Nutrition in Adolescence study . The time required to complete the 4 × 10-m shuttle run and 30-m running tests was simultaneously measured ( a ) manually with a stopwatch by both trained and untrained raters ( for interrater reliability analysis ) , and ( b ) by using photoelectric cells ( for validity analysis ) . Systematic error , r and om error , and heteroscedasticity were studied with repeated-measured analysis of variance and Bl and -Altman plots . The systematic error for untrained vs. trained raters and the untrained raters vs. photoelectric cells were in all cases ∼0.1 seconds ( p No systematic error was found between trained raters and photoelectric cells ( p > 0.05 ) . No heteroscedasticity was shown in any case ( p > 0.05 ) . The findings indicate that manual measurements by a trained rater , using a stopwatch , seem to be a valid method to assess speed and agility fitness testing in adolescents . Research ers must be trained to minimize the measurement error", "Physical fitness , participation in physical activity , fundamental motor skills and body composition are important contributors to the health and the development of a healthy lifestyle among children and youth . The New South Wales Schools Fitness and Physical Activity Survey , 1997 , was conducted to fill some of the gaps in our knowledge of these aspects of the lives of young people in New South Wales . The survey was conducted in February and March , 1997 and collected data on a r and omly-selected sample of students ( n = 5518 ) in Years 2 , 4 , 6 , 8 and 10 . Measures were taken on body composition ( height and weight , waist and hip girths , skinfolds ) , health-related fitness ( aerobic capacity , muscular strength , muscular endurance , flexibility ) , fundamental motor skills ( run , vertical jump , catch , overh and throw , foreh and strike and kick ) , self-reported physical activity , time spent in sedentary recreation , and physical education ( PE ) classes . The methods are described to assist in the development of surveys of other population s and to provoke debate relevant to the development and dissemination of st and ard approaches to monitoring the fitness , physical activity habits and body composition of Australian children and youth . Finally , we offer comments on some of the strengths and limitations of the methods employed", "Objectives To explore the extent to which muscular strength in adolescence is associated with all cause and cause specific premature mortality ( . Design Prospect i ve cohort study . Setting Sweden . Participants 1 142 599 Swedish male adolescents aged 16 - 19 years were followed over a period of 24 years . Main outcome measures Baseline examinations included knee extension , h and grip , and elbow flexion strength tests , as well as measures of diastolic and systolic blood pressure and body mass index . Cox regression was used to estimate hazard ratios for mortality according to muscular strength categories ( tenths ) . Results During a median follow-up period of 24 years , 26 145 participants died . Suicide was a more frequent cause of death in young adulthood ( 22.3 % ) than was cardiovascular diseases ( 7.8 % ) or cancer ( 14.9 % ) . High muscular strength in adolescence , as assessed by knee extension and h and grip tests , was associated with a 20 - 35 % lower risk of premature mortality due to any cause or cardiovascular disease , independently of body mass index or blood pressure ; no association was observed with mortality due to cancer . Stronger adolescents had a 20 - 30 % lower risk of death from suicide and were 15 - 65 % less likely to have any psychiatric diagnosis ( such as schizophrenia and mood disorders ) . Adolescents in the lowest tenth of muscular strength showed by far the highest risk of mortality for different causes . All cause mortality rates ( per 100 000 person years ) ranged between 122.3 and 86.9 for the weakest and strongest adolescents ; corresponding figures were 9.5 and 5.6 for mortality due to cardiovascular diseases and 24.6 and 16.9 for mortality due to suicide . Conclusions Low muscular strength in adolescents is an emerging risk factor for major causes of death in young adulthood , such as suicide and cardiovascular diseases . The effect size observed for all cause mortality was equivalent to that for well established risk factors such as elevated body mass index or blood pressure", "The purpose of this study was to examine specific aspects of the reliability and validity of age b and 1 of the Movement Assessment Battery for Children -- Second Edition ( MABC-2 ) ( Henderson , Sugden , & Barnett , 2007 ) in Greek preschool children . One hundred and eighty-three children participated in the study ; the children ranged in age from 36 to 64 months old ( M = 50 months , SD = 9 months ) . Test-retest reliability of the MABC-2 was evaluated using intraclass correlation coefficient ( ICC ) . Cronbach 's alpha for the items of each motor domain was estimated to determine internal consistency . Confirmatory factor analysis was used to examine the factorial validity of the MABC-2 test . Correlation coefficients among individual item scores and the total score were also calculated to further examine validity . The ICC for all test items was good , except for the drawing trail task , which was moderate . Cronbach 's alpha coefficient values were .51 , .70 and .66 for manual dexterity , aim ing and catching , and balance , respectively . In the confirmatory factor analysis , goodness-of-fit indices suggested a satisfactory fit of the data to the model . The correlation coefficients between each test item and the total score were moderate . The results suggest that the MABC-2 can be a reliable and valid tool for the assessment of movement difficulties among 3 - 5-year-old children", "BACKGROUND AND PURPOSE Most clinical evaluations of postural control in children are relatively subjective and have not been tested for reliability of scoring . The purpose of this study was to investigate the test-retest reliability of measurements obtained with two tiltboard tests . SUBJECTS Subjects were 18 children , aged 53 to 81 months ( mean = 64.4 , SD = 8.3 ) , who were typically developing ( TD group ) and 18 children , aged 50 to 79 months ( mean = 63.3 , SD = 8.4 ) , with developmental delays ( DD group ) . METHODS Each child was tested using the two tilt-board tests and was then retested using the same tests approximately 1 week later . The maximum angle of tiltboard tilt prior to any postural adjustment by the child was recorded . RESULTS Intraclass correlation coefficients for test-retest reliability ( two-way , r and om-effects , repeated- measures model ) ranged from .49 to .54 for the TD group and from .52 to .82 for the DD group . Angles were higher for both groups for the second test . CONCLUSION AND DISCUSSION The results suggest that these tiltboard tests do not give stable and reliable measurements across test sessions . Before these tests can be used to document change in postural control abilities across time , further research is warranted", "PURPOSE The first aim was to determine whether there is an optimal grip span for determining the maximum h and grip strength in boys and girls aged 6 to 12 years and whether the optimal grip span was related to h and span . If so , the second aim was to derive a mathematical equation relating h and span and optimal grip span . METHODS A total of 123 boys ( 9 y + /- 2 ) and 70 girls ( 8 y + /- 2 ) were evaluated . Each h and was r and omly tested on 10 occasions using 5 different grip spans , allowing a 1-minute rest between attempts . The h and span was measured from the tip of the thumb to the tip of the little finger with the h and opened widely . RESULTS An optimal grip span to determine maximum h and grip strength was identified for both genders . H and span and optimal grip span showed a significant linear association in the studied children . The equation relating grip span as a function of h and span in boys is formulated as y = x/4 + 0.44 and in girls as y = 0.3x - 0.52 , where x is the h and span ( maximal width between first and fifth fingers ) and y is the optimal grip span . CONCLUSIONS The results suggest that there is an optimal grip span to which the dynamometer should be adjusted when measuring h and grip strength in children . The optimal grip span was influenced by h and span in both genders" ]	41189f82-06ff-11f0-808a-c43d1ab1c353
BACKGROUND The efficacy of combining psychotherapy and benzodiazepines for panic disorder is unclear , despite widespread use . OBJECTIVES To examine the efficacy of the combination compared with either treatment alone . SEARCH STRATEGY R and omised trials comparing the combination of psychotherapy and benzodiazepine with either therapy alone for panic disorder were identified . The Cochrane Depression , Anxiety and Neurosis Group Studies and References Registers were search ed . References of relevant trials and other review s were checked . Experts in the field were contacted . Additional unpublished data were sought from authors of the original trials . SELECTION CRITERIA Two authors independently checked the records retrieved by the search es to identify r and omised trials comparing the combined therapy versus either of the monotherapies , among adults with panic disorder . DATA COLLECTION AND ANALYSIS Two authors independently checked eligibility , assessed quality and extracted data from the eligible trials using a st and ardised data extraction form . The primary outcome was " response " based on global judgement . R and om-effects meta-analyses were conducted , combining data from included trials . MAIN RESULTS Three trials met eligibility criteria . A 16-week behaviour therapy intervention was used in two trials , and a 12-week cognitive-behaviour therapy intervention in the third . Duration of follow-up varied , ranging from 0 to 12 months . Two trials ( total 166 participants ) provided data comparing combination with psychotherapy alone ( both using behaviour therapy ) . No statistically significant differences were observed in response during the intervention ( relative risk ( RR ) for combination 1.25 , 95 % CI 0.78 to 2.03 , P = 0.35 ) , at the end of the intervention ( RR 0.78 , 0.45 to 1.35 , P = 0.37 ) , or at the last follow-up time point , although the follow-up data suggested that the combination might be inferior to behaviour therapy alone ( RR 0.62 , 0.36 to 1.07 , P = 0.08 ) . One trial ( 77 participants ) compared combination with a benzodiazepine alone . No differences were found in response during the intervention ( RR 1.57 , 0.83 to 2.98 , P = 0.17 ) . Although the combination appeared to be superior to the benzodiazepine alone at the end of treatment ( RR 3.39 , 1.03 to 11.21 , P = 0.05 ) the finding was only borderline statistically significant , and no significant differences were observed at the 7-month follow-up ( RR 2.31 , 0.79 to 6.74 , P = 0.12 ) . AUTHORS ' CONCLUSIONS The review established the paucity of high quality evidence investigating the efficacy of psychotherapy combined with benzodiazepines for panic disorder . Currently , there is inadequate evidence to assess the clinical effects of psychotherapy combined with benzodiazepines for patients who are diagnosed with panic disorder	[ "OBJECTIVE To address the lack of a simple and st and ardized instrument to assess overall panic disorder severity , the authors developed a scale for the measurement of panic disorder severity . METHOD Ten independent evaluators used the seven-item Panic Disorder Severity Scale to assess 186 patients with principal DSM-III-R diagnoses of panic disorder ( with no or mild agoraphobia ) who were participating in the Multicenter Collaborative Treatment Study of Panic Disorder . In addition , 89 of these patients were reevaluated with the same scale after short-term treatment . A subset of 24 patients underwent two independent assessment s to establish interrater reliability . Internal consistency , convergent and discriminant validity , and sensitivity to change were also determined . RESULTS The Panic Disorder Severity Scale was associated with excellent interrater reliability , moderate internal consistency , and favorable levels of validity and sensitivity to change . Individual items showed good convergent and discriminant validity . Analysis suggested a two-factor model fit the data best . CONCLUSIONS The Panic Disorder Severity Scale is a simple , efficient way for clinicians to rate severity in patients with established diagnoses of panic disorder . However , further research with more diverse groups of panic disorder patients and with a broader range of convergent and discriminant validity measures is needed", "Studies to date on the effects of benzodiazepines on neuropsychologic function have yielded conflicting data with respect to the type , severity , and duration of deficits that may be induced by these agents . As part of a placebo-controlled trial of alprazolam-XR ( extended release ) administered in combination with cognitive-behavioral therapy in patients with panic disorder , a battery of tests was used to measure neuropsychologic function . Thirty-eight out patients were r and omly assigned to receive either alprazolam-XR or placebo . Dosages were titrated up so that the alprazolam group ( N = 18 ) received a mean dose of 4 mg/day ( reduced in two patients because of sedative side effects ) . Neuropsychologic function after 6 weeks of therapy at the target dosage was compared with baseline assessment s in each group . Both groups showed a statistically significant improvement from baseline to repeated assessment s on measures of attention , executive functioning , psychomotor speed , and visual memory ( p measures of learning , verbal memory , or reaction time , and neither group showed any deterioration from baseline to retesting in any aspect of neuropsychologic function . These findings call into question the assumption that long-term benzodiazepine therapy produces significant neuropsychologic deficit in patients with diagnosed anxiety disorders", "BACKGROUND Exposure to external phobic cues is an effective therapy for panic/agoraphobia but the value of exposure to interoceptive cues is unclear . AIMS R and omised controlled comparison in panic/agoraphobia of the effects of ( a ) external , ( b ) interceptive or ( c ) combined external and interoceptive self-exposure to ( d ) control subjects . METHOD Eighty out- patients were r and omised to a control group or to one of three forms of self-exposure treatment ( external , interoceptive , or combined ) . Each treatment included seven sessions over 10 weeks and daily self-exposure homework . Assessment s were at pre- and post-treatment and up to 1 year post-entry . Assessors remained blind during treatment . RESULTS The three self-exposure groups improved significantly and similarly at post-treatment and up to 1-year followup , and significantly more than did the control subjects . Rates of improvement on main outcome measures averaged 60 % at post-treatment and 77 % at follow-up . CONCLUSIONS The three methods of self-exposure were equally effective in reducing panic and agoraphobic symptoms in the short- and long-term", "Pre-treatment predictors of treatment outcome were examined in a group of 144 patients with panic disorder and agoraphobia r and omly allocated to alprazolam+exposure ( AE ) , placebo+exposure ( PE ) , alprazolam+relaxation ( AR ) , and placebo+relaxation ( PR ) . First-time psychotropic medication use , severity of agoraphobic disability , and longer duration of illness predicted less global improvement at post-treatment . Pre-treatment severity of agoraphobia predicted less improvement both in the short- and the long-term . Predictors of poorer outcome at 6-month follow-up were older age , past history of depression , severity of phobia targets , and longer duration of illness . Sex , source of referral , pre-treatment depression-anxiety-panic , and expectancy from treatment did not relate to outcome", "Cognitive therapy ( CT ) is a specific and highly effective treatment for panic disorder ( PD ) . Treatment normally involves 12 - 15 1-hr sessions . In an attempt to produce a more cost-effective version , a briefer treatment that made extensive use of between-sessions patient self- study modules was created . Forty-three PD patients were r and omly allocated to full CT ( FCT ) , brief CT ( BCT ) , or a 3-month wait list . FCT and BCT were superior to wait list on all measures , and the gains obtained in treatment were maintained at 12-month follow-up . There were no significant differences between FCT and BCT . Both treatments had large ( approximately 3.0 ) and essentially identical effect sizes . BCT required 6.5 hr of therapist time , including booster sessions . Patients ' initial expectation of therapy success was negatively correlated with posttreatment panic-anxiety . Cognitive measures at the end of treatment predicted panic-anxiety at 12-month follow-up", "Objective The present study examined the prevalence of panic disorder with or without agoraphobia according to DSM-IV criteria in the Swedish general population . Method Data were obtained by means of a postal survey administrated to 1000 r and omly selected adults . The panic disorder module of the World Health Organization 's Composite International Diagnostic Interview ( CIDI ) was included in the survey . Results 12-month prevalence was estimated at 2.2 % ( CI 95 % 1.02 % – 3.38 % ) . There was a significant sex difference , with a greater prevalence for women ( 5.6 % ) compared to men ( 1 % ) . Conclusion The Swedish panic disorder prevalence is relatively consistent with findings in most other parts of the western world", "In a controlled trial of alprazolam and exposure in 154 patients with panic disorder with agoraphobia , relations between panic , anticipatory anxiety , and phobic avoidance were examined . The three symptoms were independent of one another at baseline and improved largely independently during treatment ; only early improvement in avoidance predicted global improvement after treatment . Global improvement was more related to reduction of avoidance than a decrease in panics . Panic was not a valuable outcome measure in panic disorder with agoraphobia", "We analysed 113 reports published in 1980 in a sample of medical journals to relate features of study design to the magnitude of gains attributed to new therapies over old . Overall we rated 87 per cent of new therapies as improvements over st and ard therapies . The mean gain ( measured by the Mann-Whitney statistic ) was relatively constant across study design s , except for non-r and omized controlled trials with sequential assignment to therapy , which showed a significantly higher likelihood that a patient would do better on the innovation than on st and ard therapy ( p = 0.004 ) . R and omized controlled trials that did not use a double-blind design had a higher likelihood of showing a gain for the innovation than did double-blind trials ( p = 0.02 ) . Any evaluation of an innovation may include both bias and the true efficacy of the new therapy , therefore we may consider making adjustments for the average bias associated with a study design . When interpreting an evaluation of a new therapy , readers should consider the impact of the following average adjustments to the Mann-Whitney statistic : for trials with non-r and om sequential assignment a decrease of 0.15 , for non-double-blind r and omized controlled trials a decrease of 0.11", "BACKGROUND Current recommendations suggest that pharmacotherapy for patients with panic disorder should be continued for at least 1 year [ Am . J. Psychiatry 155 ( 1998 ) 1 ] , despite a paucity of data systematic ally examining outcome for periods greater than 3 - 6 months . It is critically important to obtain more information on the effectiveness of medications over time for patients who initially responded to pharmacotherapy for panic disorder . METHODS Long-term outcome was examined for 78 patients who attained a 2-month period of sustained remission on medication and received maintenance pharmacotherapy for up to 24 months during the Massachusetts General Hospital Longitudinal Study of Panic Disorder , a prospect i ve , naturalistic study . Participants were categorized by their maintenance treatment condition at remission : benzodiazepine alone ( N = 45 , 58 % ) , antidepressant alone ( N = 12 , 16 % ) , and combined treatment with a benzodiazepine and an antidepressant ( N = 21 , 27 % ) . RESULTS Approximately half ( N = 36 , 46 % ) of the patients who had achieved remission relapsed at some time over the 2-year naturalistic study period , despite continued and adequate pharmacotherapy . There was no difference in timing or frequency of relapse by type of maintenance pharmacotherapy . LIMITATIONS Interpretation of the data is limited by the naturalistic nature of the study , and by the relatively low sample size . CONCLUSIONS This data suggests that patients with panic disorder have a high rate of relapse even after acute response to pharmacotherapy , despite continued treatment . In addition , the use of combined pharmacotherapy with antidepressants and benzodiazepines does not appear to provide greater protection from relapse than monotherapy", "As part of the cross‐national collaborative panic study , a double‐blind comparison of alprazolam , imipramine and placebo was performed in Sc and inavian out patients with panic disorder according to DSM‐III ; 41 patients were r and omly allocated to each drug . Doses were increased for 3 weeks to an average of about 6 mg alprazolam , 150 mg imipramine and a corresponding number of placebo capsules , which were then given for 5 weeks . No more than supportive psychotherapy was given . Key symptoms were rated weekly . The drugs were tapered for 4 or 8 weeks and the patients were followed up for 6 months . Compliance at 3 weeks was 95 % for alprazolam , 83 % for imipramine and 88 % for placebo ; at 8 weeks 95 % for alprazolam , 73 % for imipramine and 46 % for placebo . At 3 weeks plasma determination showed that the proportion taking diazepam outside the protocol was 0 % for alprazolam , 19 % for imipramine and 31 % for placebo ; at 8 weeks the corresponding proportions were 3 % , 11 % and 16 % . Intention‐to‐treat analysis showed that freedom from panic attacks was obtained for 68 % with alprazolam , 61 % with imipramine and 34 % with placebo . Alprazolam was more effective than imipramine and placebo on anticipatory anxiety and phobic symptoms . Globally rated by physicians and patients , about 60 % had complete remission with alprazolam and imipramine and 30 % on placebo . At least partial remission was obtained in about 85 % with alprazolam , 70 % with imipramine and 40 % with placebo . Alprazolam had a more rapid onset of action than imipramine on all symptoms . Side effects were generally mild , with a preponderance of drowsiness for alprazolam and anticholinergic effects for imipramine . Tapering was uneventful without significant discontinuation phenomena . During taper and follow‐up , several patients in remission relapsed , leaving approximately 30 % patients in complete remission in all groups . To obtain more stable improvement , either long‐term drug treatment or combinations of drug treatment and psychotherapy should be evaluated", "Compared the effectiveness of cognitive therapy and performance-based exposure as treatments for panic attacks . Subjects were 48 panicky individuals selected without regard to agoraphobic disability , and who varied widely in that respect . Subjects were assigned r and omly to either cognitive treatment , performance-based exposure treatment , a combined cognitive/performance treatment , or a no-treatment control condition . All three treatments led to marked and enduring improvements in panic , and did not differ from one another in effectiveness , whereas the control condition produced little benefit . However , on several measures of phobia and panic-related cognitions , performance exposure was significantly more effective than cognitive therapy . Degree of agoraphobic disability had a significant bearing on panic treatment effectiveness . Whereas 94 % of the low agoraphobia Ss were free of panic after treatment , only 52 % of the high agoraphobia Ss became panic-free . The findings suggest that when panic treatment research excludes people with serious phobias , as it has routinely done in recent years , an overly positive estimate of panic treatment effectiveness can result", "Fifty-seven chronic agoraphobic out patients were treated by 12 hours of exposure in vivo on four days over two weeks to check the effects of oral diazepam versus placebo during group exposure , group versus individual exposure , and high versus medium anxiety arousal during individual exposure . The controlled parallel design allowed comparative evaluation of each treatment condition to six months follow-up . Assessment was blind with respect to drug and psychological treatment . Patients in all treatment conditions improved significantly in phobias and in related life areas . Outcome to group exposure on phobias and other measures was similar in all three drug conditions ( placebo , waning diazepam , peak diazepam ) with no significant differences between them . Diazepam patients had significantly less discomfort than placebo patients during group exposure treatment . Group exposure patients improved slightly but significantly more than individual exposure patients on non-phobic measures , though group exposure was accompanied by more panics during treatment yet was easier to run by the therapist . Individual exposure under high anxiety arousal was no more therapeutic than with lower anxiety . Diazepam is a mild palliative during group exposure but does not facilitate outcome to treatment . Group exposure in vivo is mildly facilitatory for outcome compared with individual exposure . Anxiety evocation during treatment was not therapeutically helpful", "The objectives of this prospect i ve study were to calculate incidence rates for fall-related hospitalization , to compare the effect of risk factors among benzodiazepine ( BZD ) users and unexposed controls , and to examine variations in risks according to length of time following a BZD prescription . Data were derived from Saskatchewan Health linked data bases , leading to information on 468 hospitalizations for injury due to falls among a study population of 321422 . Incidence rates per 10000 within 28 days of the prescription fill date were 26.2 , 12.1 and 9.0 for BZD sedative users , BZD tranquillizer users and for unexposed controls , respectively . Incidence rates increased with age , and were higher for women than for men . Results from multivariate logistic regression models also showed a greater risk of falling for BZD users but the odds ratio was higher for men than for women . A history of treatment for alcohol abuse was a very strong risk factor for falls among both men ( odds ratio , 10.7 ) and women ( odds ratio , 4.3 ) . The highest risk of serious injury due to falls was within 15 days of filling the prescription , with an odds ratio of 3.6 for BZD sedatives and 2.6 for BZD tranquillizers . Risk decreased with further increase of time after the BZD fill date . For the individual BZD , flurazepam and triazolam showed the highest increase in risk with odds ratios of 3.4 and 2.7 , respectively , while oxazepam , lorazepam and diazepam showed odds ratios of 2.2 , 2.0 and 1.8 ( all odds ratios mentioned are statistically significant at p < 0.05 )", "Controlled clinical trials of the treatment of acute myocardial infa rct ion offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment . A group of 145 papers was divided into those in which the r and omization process was blinded ( 57 papers ) , those in which it may have been unblinded ( 45 papers ) , and those in which the controls were selected by a nonr and om process ( 43 papers ) . At least one prognostic variable was maldistributed ( P less than 0.05 ) in 14.0 per cent of the blinded-r and omization studies , in 26.7 per cent of the unblinded-r and omization studies , and in 58.1 per cent of the nonr and omized studies . Differences in case-fatality rates between treatment and control groups ( P less than 0.05 ) were found in 8.8 per cent of the blinded-r and omization studies , 24.4 per cent of the unblinded-r and omization studies , and 58.1 per cent of the nonr and omized studies . These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration", "The present study examined the efficacy of an 8-wk , cognitive-behavioral group treatment for panic disorder . Patients meeting DSM-III-R criteria for panic disorder with or without agoraphobia were r and omly assigned to treatment ( N = 34 ) or delayed treatment control ( N = 33 ) . The treatment consisted of : ( a ) education and corrective information ; ( b ) cognitive therapy ; ( c ) training in diaphragmatic breathing ; and ( d ) interoceptive exposure . At posttreatment , 85 % of treated Ss were panic free , compared to 30 % of controls . Treated Ss also showed clinical ly significant improvement on indices of anxiety , agoraphobia , depression and fear of fear . Recovery , as estimated conservatively by the attainment of normal levels of functioning on each of the major clinical dimensions of the disorder ( i.e. panic , anxiety and avoidance ) , was achieved in 64 % of the treated Ss and 9 % of the controls . At the 6 month follow-up , 63 % of the treated patients met criteria for recovery . These findings mirror those from recently-completed trials of individually-administered cognitive-behavioral treatment , and suggest that CBT is a viable alternative to pharmacotherapy in the treatment of panic disorder", "The intensity of putative benzodiazepine withdrawal symptoms was evaluated as part of a double blind placebo-controlled study of benzodiazepines and behaviour therapy in the management of agoraphobia . During the first phase of that study , some subjects were switched from low dose diazepam to placebo , and others remained on diazepam . Symptoms were evaluated in long-term benzodiazepine users ( n=30 ) and non-users ( n=32 ) when they first entered the study and 4 weeks later , after both groups had been r and omized to either diazepam or placebo , using eight analog rating scales measuring commonly reported withdrawal symptoms . At baseline , both users and non-users reported a substantial number of symptoms , with higher levels in the more anxious patients , but no differences between groups . After the transition to either diazepam or placebo , the users switched to placebo reported significantly higher levels of symptoms than users switched to diazepam and non-users combined . Multiple regression analysis suggested that the increase in symptoms was associated with the increase in anxiety , which was higher in the withdrawing group than the other three groups . These results raise questions concerning the extent to which withdrawal symptoms uniquely characterize benzodiazepine withdrawal . They confirm the common assumption that an increase in symptoms often accompanies withdrawal from benzodiazepines , but suggest that such symptoms are not so intense as to make withdrawal excessively difficult , at least in low-dose users", "BACKGROUND The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects . The efficacy of alprazolam and placebo in panic disorder with agoraphobia , and the side-effect and adverse effect profiles of both drug groups were measured . METHOD In London and Toronto 154 patients who met DSM-III criteria for panic disorder with agoraphobia were r and omised to alprazolam or placebo . Subjects in each drug group also received either exposure or relaxation . Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16 . RESULTS Mean alprazolam dose was 5 mg daily . Compared with placebo subjects , alprazolam patients developed more adverse reactions ( 21 % v. 0 % ) of depression , enuresis , disinhibition and aggression ; and more side-effects , particularly sedation , irritability , impaired memory , weight loss and ataxia . Side-effects tended to diminish during treatment but remained significant at week 8 . Despite this , the drop-out rate was low . CONCLUSIONS Alprazolam caused side-effects and adverse effects during treatment but many patients were willing to accept these", "OBJECTIVE The authors investigated whether cognitive behavioral treatment could facilitate discontinuation of alprazolam therapy and maintenance of drug abstinence among panic disorder patients treated with alprazolam doses sufficient to suppress spontaneous panic attacks . METHOD Twenty-one out patients who met DSM-III-R criteria for panic disorder with mild to severe agoraphobia were made panic-free with alprazolam ( mean dose = 2.2 mg/day ) and were then r and omly assigned to receive either supportive drug maintenance and slow , flexible drug taper or an identical medication treatment plus 12 weeks of concurrent , individual cognitive behavioral treatment . Taper in the combined treatment group was sequenced to conclude before cognitive behavioral treatment ended . RESULTS Twenty subjects completed the study . There was no significant difference between groups in the rate of alprazolam discontinuation ( 80 % and 90 % , respectively , in the alprazolam-only group and the combined treatment group ) . However , during the 6-month follow-up period , half of the subjects who discontinued alprazolam without cognitive behavior therapy , but none of those who were given cognitive behavior therapy , relapsed and resumed alprazolam treatment . CONCLUSIONS Cognitive behavioral treatment administered in parallel with alprazolam maintenance and taper was effective in preventing relapse after drug discontinuation . The results warrant further research on the thoughtful integration of these two therapeutic modalities", "Panic disorder , which is found in about 1.5 percent of the population at some time in their lives , includes recurrent episodes of sudden , unpredictable , intense fear accompanied by symptoms such as palpitations , chest pain , and faintness . Panic attacks , which do not meet these diagnostic criteria fully , are two to three times more prevalent . Since panic symptoms can mimic those of other medical disorders , patients with these symptoms use medical services frequently . To determine the risk of suicidal ideation and suicide attempts in panic disorder and attacks , we studied a r and om sample of 18,011 adults drawn from five U.S. communities . Subjects who had panic disorder , as compared with other psychiatric disorders , had more suicidal ideation and suicide attempts , with an adjusted odds ratio for suicide attempts of 2.62 ( 95 percent confidence interval , 1.83 to 3.74 ) . The odds ratio was 17.99 ( 95 percent confidence interval , 12.18 to 26.58 ) when the group with panic disorder was compared with subjects who had no psychiatric disorder . Twenty percent of the subjects with panic disorder and 12 percent of those with panic attacks had made suicide attempts . These results could not be explained by the coexistence of major depression or of alcohol or drug abuse . We conclude that panic disorder and attacks are associated with an increased risk of suicidal ideation and suicide attempts . Physicians working in general medical setting s and emergency departments should be alert to this problem", "Eighty clients enrolled in a managed care health plan who identified panic disorder as their primary presenting problem were r and omly assigned to treatment by a therapist recently trained in a manual-based empirically supported psychotherapy or a therapist conducting treatment as usual ( TAU ) . Participants in both conditions showed significant change from pre- to posttreatment on a number of measures . Those receiving panic control therapy ( PCT ) showed greater levels of change than those receiving TAU . Among treatment completers , an average of 42.9 % of those in PCT and 18.8 % in TAU achieved clinical ly significant change across measures . The results are discussed with reference to the dissemination of PCT and other evidence -based psychotherapies to clinical practice setting", "OBJECTIVE How far the results of r and omized controlled studies apply to everyday care can not be judged without regular measurements of outcomes in daily practice . We report on systematic data from a 3-year naturalistic prospect i ve study on panic disorder-agoraphobic ( PDA ) patients treated with antidepressants in a setting of routine clinical practice . Our aim is to describe the evolution of PDA in relation to the treatments employed , and to explore demographic and clinical characteristics that might be predictive of outcome . METHODS 326 DSM-III-R PDA patients treated with antidepressants in a setting of routine clinical practice were included in a 3-year naturalistic prospect i ve study . We utilized structured and semi-structures instruments , including the Structured Clinical Interview for Diagnosis and the Longitudinal Interview Follow-up Examination . The main antidepressants used were imipramine ( 39 % ) , clomipramine ( 28.5 % ) and paroxetine ( 23.3 % ) ; only 9 % of patients received other antidepressants . RESULTS 147 patients ( 45.1 % ) stayed on medication throughout the entire period of the follow-up . Of those who interrupted the treatment , 38 % stayed in remission . The probability of achieving at least one remission during the 3-year follow-up period was 96.5 % for PD and 95.9 % for Agoraphobia . Relapses after a period of at least 2 months of complete remission were also common , and the probability of presenting at least one relapse during the 3-years follow-up period was 67.1 % for PD and 39 % for Agoraphobia . The longest period of remission of PD is associated with low severity , medium-lasting course in patients with an onset of the illness in young adulthood . Less severe agoraphobia associated with moderately severe panic attacks appears to confer a better control of phobic behavior . All three major drugs were reasonably well tolerated ( only 9 % dropped out because of side effects ) , with sexual dysfunction and increased appetite being the most common side effects at the last evaluation ; in the first phase of the treatment anticholinergic effects and jitteriness were more common with TCAs . CONCLUSION Both classical antidepressants and paroxetine emerge as a useful treatment in the long-term management of PDA ; paroxetine appears particularly useful in PDA patients because it was significantly less likely to induce jitteriness , thereby reducing barriers to compliance", "To examine the effect of treatment on lactate-induced anxiety in a controlled study , we infused 44 panic disorder patients with lactate and placebo before and after eight weeks of double-blind treatment with imipramine , diazepam , or placebo . During treatment , both imipramine and diazepam groups improved more than the placebo group . After treatment , patients in both the imipramine and diazepam groups had significantly less anxiety than the placebo patients when reinfused with lactate . In addition , imipramine decreased posttreatment panic attack frequency and diazepam decreased the perceived severity of posttreatment lactate-induced panic attacks . This study demonstrates that diazepam , like imipramine , is an effective treatment for panic disorder , and that both imipramine and diazepam blunt lactate-induced anxiety in a placebo controlled study", "OBJECTIVE The primary disadvantage of high-potency benzodiazepine treatment for panic disorder is the difficulty of discontinuing the treatment . During treatment discontinuation , new symptoms may emerge and anxiety may return , preventing many patients from successfully discontinuing their treatment . In this controlled , r and omized trial the authors investigated the efficacy of a cognitive-behavioral program for patients with panic disorder who were attempting to discontinue treatment with high-potency benzodiazepines . METHOD Out patients treated for panic disorder with alprazolam or clonazepam for a minimum of 6 months and expressing a desire to stop taking the medication ( N = 33 ) were r and omly assigned to one of two taper conditions : a slow taper condition alone or a slow taper condition in conjunction with 10 weeks of group cognitive-behavioral therapy . RESULTS The rate of successful discontinuation of benzodiazepine treatment was significantly higher for the patients receiving the cognitive-behavioral program ( 13 of 17 ; 76 % ) than for the patients receiving the slow taper program alone ( four of 16 ; 25 % ) . There was no difference in the likelihood of discontinuation success between the patients treated with alprazolam and those who received clonazepam . At the 3-month follow-up evaluation , 77 % of the patients in the cognitive-behavioral program who successfully discontinued benzodiazepine treatment remained benzodiazepine free . CONCLUSIONS These findings support the efficacy of cognitive-behavioral interventions in aiding benzodiazepine discontinuation for patients with panic disorder", "A cross-national r and omised trial of alprazolam for chronic panic disorder with agoraphobia was run . Compared with previous trials it had three new features : an exposure therapy contrast group , a six-month treatment-free follow-up , and a low rate of early placebo drop-outs ( ' non-evaluables ' ) . The dose of alprazolam was high ( 5 mg/day ) . The 154 patients had eight weeks of : alprazolam and exposure ( combined treatment ) ; or alprazolam and relaxation ( a psychological placebo ) ; or placebo and exposure ; or placebo and relaxation ( double placebo ) . Drug taper was from weeks 8 to 16 . Follow-up was to week 43 . Results were similar at both sites . Treatment integrity was good . All four treatment groups , including double placebo , improved well on panic throughout . On non-panic measures , by the end of treatment , both alprazolam and exposure were effective , but exposure had twice the effect size of alprazolam . During taper and follow-up , gains after alprazolam were lost , while gains after exposure were maintained . Combining alprazolam with exposure marginally enhanced gains during treatment , but impaired improvement thereafter . The new features put previous trails in a fresh light . By the end of treatment , though gains on alprazolam were largely as in previous studies , on phobias and disability they were half those with exposure . Relapse was usual after alprazolam was stopped , whereas gains persisted to six-month follow-up after exposure ceased . Panic improved as much with placebo as with alprazolam or exposure", "23 patients with a diagnosis of panic disorder with agoraphobia were r and omly assigned to 8 weeks ' treatment with alprazolam or placebo . They filled in self-ratings before and after treatment and competed on a competitive reaction time task , design ed to measure behavioural aggression , after 8 weeks ' treatment . Patients taking both alprazolam and placebo rated decreased anxiety after 8 weeks ' treatment but those on alprazolam also tended to report less hostility . On the behavioural task , patients on alprazolam behaved more aggressively in response to provocation . This is the first study to confirm clinical reports of benzodiazepine-induced dyscontrol on an objective laboratory measure . It is important that it is followed up in a larger group of patients", "In a double-blind controlled study lasting 8 weeks , 50 anxious psychoneurotic out patients with a primary diagnosis of generalized anxiety or panic disorder were r and omly assigned to alprazolam ( n=30 ) , a new benzodiazepine , or placebo ( n=20 ) , after a washout period of 1 week . Alprazolam at dosages between 0.25 and 3 mg/day was found to be significantly better than placebo in the treatment of either disorder . The finding that alprazolam was effective in the treatment of panic disorder is of interest as this diagnostic category is usually treated with tricyclic antidepressants or MAO inhibitors", " Forty-eight patients currently experiencing panic attacks were r and omly assigned to double-blind treatment with alprazolam , diazepam , or placebo . Efficacy was assessed using the Hamilton Rating Scale for Anxiety and a panic attack frequency rating scale . Results indicate that the two active treatments appeared equally effective in reducing both the frequency of panic attacks and the severity of generalized anxiety when compared with placebo . Overall , these data support the use of benzodiazepines in the treatment of panic disorder", "It has been suggested that maintenance treatment of patients who have remitted panic disorder with agoraphobia beyond the six months of acute phase imipramine treatment may decrease the risk of relapse . This study further explores the relationship between relapse and duration of imipramine treatment in this population . Fifty-one patients , all in remission at the end of six months acute phase open trial with imipramine 2.25 mg/kg/day and r and omized to double-blind maintenance or placebo substitution , discontinued imipramine treatment eventually and were followed over a 12-month risk period : 27 during first year placebo substitution , 7 after 12 months of imipramine maintenance in placebo substitution , and 17 after variable duration s of imipramine maintenance in open discontinuation . There were no behaviorally oriented interventions or instructions at any time during the acute and maintenance phases of treatment or during imipramine discontinuation . Duration of imipramine treatment , the method of discontinuation ( open versus placebo substitution ) , or any of the 9 variables from the demographic , clinical , and open treatment domains that were entered in a Cox proportional hazard model did not predict relapse . The rate of relapse after only 6 months of treatment ( 10 out of 27 , 37 % ) was identical to the rate of relapse after 12 to 30 months of treatment ( 9 out of 24 , 37.5 % ) . The results suggest a lack of specific protective effects beyond prophylaxis and underscore the difficulty in predicting relapse in fully remitted panic disorder with agoraphobia patients . Early detection of relapse in patients who discontinue treatment may be a viable alternative to prediction", "Severely agoraphobic patients were treated with a combination of imaginal flooding and exposure to phobic situations in practice . This behavioural treatment was found to be more effective if given together with an anxiolytic drug ( diazepam ) . There was no indication that the therapeutic changes induced were smaller or more transient if the patient attributed them to the drug rather than to the behavioural treatment ; instead there appeared to be a placebo-like effect as well as the drug effect", "The present study investigated the impact of pre-existing pharmacotherapy regimes on the long-term outcome of brief intensive group cognitive-behavioural therapy ( BIGCBT ) in the treatment of panic disorder with or without agoraphobia in 106 patients ( 74 females ) . Forty patients were allocated to BIGCBT without medication , 40 to BIGCBT plus anti-anxiety medication , 10 to BIGCBT plus anti-depressant medication and 16 to BIGCBT plus combined anti-anxiety and anti-depressant medications . The mean follow-up period was 3.2 yr and ranged from 1.1 to 6.2 yr . The results demonstrated that patients who received BIGCBT concurrent with pre-existing medication regimes did not differ significantly ( P > 0.001 ) from each other or from patients who underwent BIGCBT without medication on any of the dependent measures either at pre-treatment assessment or long-term follow-up . However , BIGCBT ( with or without pharmacotherapy ) was associated with significant ( P long-term improvements in frequency of panic attacks , avoidance behaviour and question naire measures of anxiety , depression and agoraphobia . Furthermore , the large majority ( 80 % ) of patients in the BIGCBT without medication group remained medication-free at long-term follow-up . Of those patients who underwent BIGCBT concurrent with pre-existing pharmacotherapy , a large percentage ( 44 % ) reported no longer taking medication for their condition at long-term follow-up . Overall , it is concluded that pre-existing medication regimes ( anti-anxiety , anti-depressant or combinations of these ) do not significantly enhance or detract from the long-term outcome of a BIGCBT program used in the treatment of panic disorder and agoraphobia", "BACKGROUND Benzodiazepines ( BZs ) can impair explicit memory after a single dose and also when taken repeatedly for treatment of anxiety disorders . A previous study with agoraphobia/panic patients found that the BZ alprazolam impaired memory during an 8-week treatment and residual impairments were still manifest several weeks after drug withdrawal ( Curran et al. 1994 ) . The present study followed up the same group of patients 3.5 years after treatment to determine whether those memory impairments persisted . METHOD Thirty-one patients , 15 who had originally been treated with alprazolam and 16 with placebo , were assessed on a battery of psychometric tests and self-rating scales . RESULTS Ex-alprazolam patients performed at the same levels as ex-placebo patients on the memory task and on other objective tests . Performance levels of both groups were similar to pre-treatment baselines , however there were differences in subjective ratings whereby ex-alprazolam patients rated themselves as less attentive and clear headed and more incompetent and clumsy than ex-placebo patients . CONCLUSIONS Explicit memory impairments found while patients were taking alprazolam and weeks after drug withdrawal did not persist 3.5 years later . We suggest that the memory impairments observed in our previous study weeks after withdrawal of alprazolam were not residual effects of alprazolam but rather were due to the drug 's interference with practice effects on the tests and habituation of anxiety over repeated exposure to the test situation", "OBJECTIVE This study sought to determine the short- and long-term effects of focused cognitive therapy for panic disorder . METHOD Thirty-three psychiatric out patients with the DSM-III diagnosis of panic disorder were r and omly assigned to either 12 weeks of individual , focused cognitive therapy or 8 weeks of brief supportive psychotherapy based on principles of client-centered therapy . The patients who received supportive psychotherapy were subsequently given the opportunity to cross over to cognitive therapy for 12 weeks . Patients were rated for panic and depression before therapy , after 4 and 8 weeks of therapy , and at 6-month and 1-year follow-up . RESULTS Clinician ratings and self-ratings of panic frequency and intensity indicated that the focused cognitive therapy group achieved significantly greater reductions in panic symptoms and general anxiety after 8 weeks of treatment than did the group that received brief supportive psychotherapy . At 8 weeks , 71 % of the cognitive therapy group were panic free , compared to 25 % of the psychotherapy group . Moreover , 94 % of the psychotherapy patients elected to cross over to 12 weeks of cognitive therapy . At 1-year follow-up , 87 % of the group that received cognitive therapy only and 79 % of the group that crossed over into cognitive therapy remained free of panic attacks . CONCLUSIONS Focused cognitive therapy offers a promising nonpharmacological alternative for the treatment of panic disorder", "BACKGROUND Alprazolam has proven efficacy as a treatment for panic disorder , but the place of other benzodiazepines is less well established . METHOD To compare the efficacy and tolerability of diazepam and alprazolam for the disorder , a placebo-controlled , double-blind trial was undertaken in two sites . Two hundred forty-one subjects with panic disorder or agoraphobia with panic attacks were r and omly assigned to flexible doses of diazepam , alprazolam , or placebo for 8 weeks . RESULTS At the end of the trial , over 60 % of subjects taking either diazepam or alprazolam were at least moderately improved compared with less than 30 % of those taking placebo . On all measures of efficacy , subjects taking diazepam and alprazolam showed an equally favorable response . Despite some sedation early in the trial , both drugs were tolerated well . More severely ill subjects responded less well to either benzodiazepine . CONCLUSION The results indicate that diazepam is an effective alternative to alprazolam for the treatment of panic disorder", "Benzodiazepines ( BZs ) produce transient antero grade amnesia when given to normal subjects . The present longitudinal study assessed whether BZs impair memory functions in a clinical ly anxious group . Eighty-two agoraphobics with panic disorder were r and omly allocated to one of four treatment groups result ing from a combination of two drug treatments ( alprazolam or placebo ) and two psychological treatments ( exposure or relaxation ) . Of these , 38 subjects were assessed on a range of objective and subjective indices of memory and mood at three time points : before treatment , after 8 weeks of treatment and again at 24 weeks when patients had been free of medication from 5 - 8 weeks . Alprazolam produced pronounced impairments on a word recall task . At the 24-week medication-free follow-up , alprazolam patients were still impaired on the task compared with placebo patients . Alprazolam did not impair performance on an implicit memory task and did not affect digit span . Differences between psychological treatments emerged mainly in subjective memory effects . Findings are discussed in terms of the specificity of BZ-induced amnesia and differential tolerance to the varying effects of BZs . Implication s are drawn out for the patient 's ability to function optimally in daily life while taking alprazolam", "Panic disorder ( PD ) is associated with significant social and health consequences . The present study examined the impact of treatment on PD patients ' quality of life . Patients ( N = 156 ) meeting DSM-III-R ( Diagnostic and Statistical Manual of Mental Disorders [ 3rd ed . , rev . ] ; American Psychiatric Association , 1987 ) criteria for PD with agoraphobia were r and omly assigned to group cognitive-behavioral treatment ( CBT ) or a delayed-treatment control . An assessment battery measuring the major clinical features of PD as well as quality of life was administered at baseline ( Week 0 ) , post-treatment ( Week 9 ) and 6-month follow-up ( Week 35 ) . Consistent with previous studies , PD patients displayed significant impairment in quality of life at intake . Compared with delayed-treatment control participants , CBT-treated participants showed significant reductions in impairment that were maintained at follow-up . Consistent with prediction , anxiety and phobic avoidance were significantly associated with quality of life , whereas frequency of panic attacks was not", "In a study design ed to evaluate the impact of benzodiazepine use on the outcome of behaviour therapy , 91 , severe , chronic agoraphobics ( 46 BDZ users and 45 non-users ) were r and omly allocated on a double-blind basis to in vivo exposure with low-dose diazepam ( ED ) or placebo ( EP ) . Drug doses were adjusted on the basis of weekly psychiatric assessment s over weeks 1 - 4 . Patients had 8 x 2 hr exposure sessions ( weeks 5 - 12 ) and were then withdrawn from medication ( weeks 13 - 16 ) . Re- assessment s were completed at weeks 4 , 12 and 16 , and follow-up assessment s at approx 20 , 46 and 72 weeks . In the analysis of the results , the clinical outcome was evaluated in relation to the therapeutic regime ( ED vs EP ) and prior BDZ use ( users vs non-users ) . The results showed that the ED group had greater changes in anxiety than the EP group during the drug manipulation phases ( anxiety increasing during BDZ withdrawal ) . There were no group differences in agoraphobic symptoms and no evidence that the outcome of the behavior therapy was significantly affected by concurrent BDZ treatment . There were significant improvements in agoraphobic symptoms over the treatment period , with no evidence for relapse of treatment gains on withdrawal from BDZ , nor for differential responses over the one year follow-up . Initial differences between users and non-users were less marked than expected , although there was a trend for more drop-outs among users across both ED and EP groups", "Cognitive-behavioral therapy ( CBT ) is the psychological treatment of choice for panic disorder ( PD ) . However , given limited access to CBT , it must be delivered with maximal cost-effectiveness . Previous research ers have found that a brief computer-augmented CBT was as effective as extended therapist-delivered CBT . To test this finding , this study r and omly allocated 186 patients with PD across 2 sites in Scotl and and Australia to 12 sessions of therapist-delivered CBT ( CBT12 ) , 6 sessions of therapist-delivered ( CBT6 ) or computer-augmented CBT ( CBT6-CA ) , or a waitlist control . On a composite measure , at posttreatment , the outcome for CBT 12 was statistically better than the outcome for CBT6 . The outcome for CBT6-CA fell between CBT12 and CBT6 , but could not be statistically distinguished from either treatment . The active treatments did not differ statistically at 6-month follow-up . The study provided some support for the use of computers as an innovative adjunctive-therapy tool and merits further investigation", "BACKGROUND We determined whether blindness in a double-blind r and omized controlled trial of alprazolam and exposure therapies in patients with panic disorder and agoraphobia was maintained in assessors and patients , what were the factors related to \" unblinding , \" and whether unblinding was associated with clinical outcome . METHOD In 129 patients with panic disorder and agoraphobia who were r and omized to alprazolam-exposure , placebo-exposure , alprazolam-relaxation , or placebo-relaxation conditions , blindness was tested at the end of treatment by the independent assessors ' and patients ' classification of the treatment condition . RESULTS Assessors ' classifications were correct in 82 % of the alprazolam group and 78 % of the placebo group ; corresponding figures for patients ' classifications were 73 % and 70 % , respectively . Factors associated with unblinding included drug side effects but not assessors ' ratings of treatment outcome . CONCLUSION Judgment of the validity of the outcome of a r and omized controlled trial is easier if the report notes not only the use of a double-blindness procedure but also details how blind the raters remained and how any unblinding affected their ratings of clinical outcome", "Preliminary reports of discontinuation of alprazolam therapy in patients with panic disorder have revealed worsening of symptoms despite gradual withdrawal of medication . In this study , 126 patients with panic disorder and phobic avoidance received either alprazolam or placebo in doses of 2 to 10 mg daily for eight weeks . The medication was tapered over a period of four weeks , and patients were observed for another two weeks after all medication was discontinued . Sixty of the 63 alprazolam-treated patients and 49 of the 63 placebo-treated patients entered the taper and discontinuation study . After improvement in the active treatment period , the alprazolam-treated group had significant relapse between the first and last week of taper . However , during the second postdiscontinuation week , outcome scores were not significantly different from those of the placebo-treated group who did not deteriorate during taper . Twenty-seven percent of the alprazolam-treated group reported a rebound of panic attacks during taper and 13 % reported a rebound of anxiety on the Hamilton Anxiety Scale . No serious or life-threatening withdrawal symptoms were reported , but distinct , transient , mild to moderate withdrawal syndrome occurred in 35 % of the alprazolam-treated group and in none of the placebo-treated group . The coexistence of symptom rebound and a withdrawal syndrome occurred in 10 % of the alprazolam-treated group , but both subsided by the end of the second week without alprazolam . We recommend that patients with panic disorder be treated for a longer period , at least six months , and that medication be tapered over a more prolonged period , at least eight weeks , especially where high doses are employed", "The response to diazepam and propranolol hydrochloride was compared in 21 patients who ( with one exception ) met DSM-III criteria for panic disorder and agoraphobia . Each drug was administered for two weeks in double-blind fashion according to a crossover design . The response to diazepam was significantly superior on all measures . By observer rating , 18 patients showed at least moderate improvement with diazepam compared with seven receiving propranolol . Panic attacks and phobic symptoms responded to diazepam , but not to propranolol . The results suggest that benzodiazepines constitute effective short-term treatment for these newly defined disorders", " Patients with panic disorder plus agoraphobia had 8 weeks of drug treatment ( alprazolam or placebo ) plus psychological treatment ( exposure or relaxation ) . At the end of treatment at week 8 , 40 patients who had become much/very much improved rated how much their gains were attributable to medication or to their own efforts . During the tapering-off to week 16 , and treatment-free follow-up to week 43 , patients who at week 8 had attributed their gains to medication and felt less confident in coping without tablets had more severe withdrawal symptoms and greater loss of gains than did patients who at week 8 had attributed their gains to their own efforts during treatment . Baseline illness severity , greater age , higher expectations from drug treatment , and more side-effects of drugs during treatment all predicted more external attributions ( i.e. to the effect of drugs ) but did not independently predict relapse . Patients on alprazolam compared with placebo had more drug attributions . Though drug attributions predicted relapse in both alprazolam and placebo groups , predictions were stronger in the alprazolam group" ]	41189fbe-06ff-11f0-808a-c43d1ab1c353
Background This review examines evidence for an association between computer work and carpal tunnel syndrome ( CTS ) . Methods A systematic review of studies of computer work and CTS was performed . Supplementary , longitudinal studies of low force , repetitive work and CTS , and studies of possible pathophysiological mechanisms were evaluated . Results Eight epidemiological studies of the association between computer work and CTS were identified . All eight studies had one or more limitation including imprecise exposure and outcome assessment , low statistical power or potentially serious biases . In three of the studies an exposure-response association was observed but because of possible misclassification no firm conclusions could be drawn . Three of the studies found risks below 1 . Also longitudinal studies of repetitive low-force non-computer work ( n = 3 ) were review ed but these studies did not add evidence to an association . Measurements of carpal tunnel pressure ( CTP ) under conditions typically observed among computer users showed pressure values below levels considered harmful . However , during actual mouse use one study showed an increase of CTP to potentially harmful levels . The long term effects of prolonged or repeatedly increased pressures at these levels are not known , however . Conclusion There is insufficient epidemiological evidence that computer work causes CTS	[ "This study followed workers over an extended period of time to identify factors which may influence the onset of Carpal Tunnel Syndrome ( CTS ) . The purpose was to evaluate incidence of CTS and to create a predictive model of factors that play a role in the development of CTS . This prospect i ve study followed 432 industrial and clerical workers over 5.4 years . Incident cases were defined as workers who had no prior history of CTS at baseline testing and were diagnosed with CTS during the follow-up period or at the follow-up screening . On the basis of logistic regression , significant predictors for CTS include baseline median-ulnar peak latency difference , a history of wrist/h and /finger tendonitis , a history of numbness , tingling , burning , and /or pain in the h and , and work above the action level of the peak force and h and activity level threshold limit value . This longitudinal study supports findings from previous cross-sectional studies identifying both work related ergonomic stressors and physical factors as independent risk factors for CTS", "BACKGROUND A prospect i ve study of computer users was performed to determine the occurrence of and evaluate risk factors for neck or shoulder ( N/S ) and h and or arm ( H/A ) musculoskeletal symptoms ( MSS ) and disorders ( MSD ) . METHODS Individuals ( n = 632 ) newly hired into jobs requiring > or = 15 hr/week of computer use were followed for up to 3 years . At study entry , workstation dimensions and worker postures were measured and medical and psychosocial risk factors were assessed . Daily diaries were used to document work practice s and incident MSS . Those reporting MSS were examined for specific MSD . Incidence rates of MSS and MSD were estimated with survival analysis . Cox regression models were used to evaluate associations between participant characteristics at entry and MSS and MSD . RESULTS The annual incidence of N/S MSS was 58 cases/100 person-years and of N/S MSD was 35 cases/100 person-years . The most common N/S MSD was somatic pain syndrome . The annual incidence of H/A MSS was 39 cases/100 person-years and of H/A MSD was 21 cases/100 person-years . The most common H/A disorder was deQuervain 's tendonitis . Forty-six percent of N/S and 32 % of H/A MSS occurred during the first month of follow-up . Gender , age , ethnicity , and prior history of N/S pain were associated with N/S MSS and MSD . Gender , prior history of H/A pain , prior computer use , and children at home were associated with either H/A MSS or MSD . CONCLUSIONS H/A and N/S MSS and MSD were common among computer users . More than 50 % of computer users reported MSS during the first year after starting a new job", "The purpose of the study was to determine whether abnormal median sensory nerve conduction among asymptomatic workers was predictive of future symptoms suggestive of carpal tunnel syndrome ( CTS ) . This was a prospect i ve study involving 77 workers who were identified as asymptomatic cases with electrodiagnostic findings of median mononeuropathy compared to an age- and sex-matched control group . Follow-up was completed an average of 70 months later , and subjects who reported pain , numbness , tingling , or burning in the distribution of the median nerve , based upon a h and diagram , were classified as having CTS symptoms . The follow-up participation rate was 70 % . Among subjects with abnormal median sensory latencies , 23 % went on to develop symptoms consistent with CTS within the follow-up period , compared with 6 % in the control group ( P= .010 ) . Age and h and repetition were also risk factors for CTS , but the majority of asymptomatic workers with a median mononeuropathy do not become symptomatic over an extended time", "Objectives To study whether different information on a study may influence the reporting of symptoms suspected to be related to poor indoor climate at the workplace or at home . Methods A question naire was mailed to a r and om sample ( n=4,000 ) of the general population in Denmark . The participants were r and omly allocated to two study groups , each group receiving a slightly different information letter . There were 2,710 subjects ( 67.8 % ) who completed the question naire , and 2,164 subjects , who were in employment , were included in the study . All subjects were informed that the purpose of the study was to assess the prevalence of non-specific symptoms related to the indoor climate at work and in dwellings . However , in the letter to one study group it was stated that knowledge was especially lacking about health effects related to the indoor climate at work ( n=1,468 ) . To the other study group the words at work were replaced with at home ( n=696 ) . The question naires were similar for each study group . Results The prevalence rates of symptoms were similar , but reporting of work-relatedness and home-relatedness differed considerably between the two study groups . If the information letter focused slightly more on the workplace than the home , the subjects were more likely to report that their symptoms were work-related ( significant unadjusted odds ratios ( ORs ) between 1.8 and 5.5 ) . We found that adjusting the results for several confounders mainly led to higher estimates of ORs . Likewise , the subjects reported more home-related symptoms if focus was on the environment at home ( significant unadjusted ORs between 5.7 and 20.6 ) . Conclusions The information about a study may play an important role in the reporting of symptoms", "CONTEXT Carpal tunnel syndrome ( CTS ) is a cause of pain , numbness , and tingling in the h and s and is an important cause of work disability . Although high prevalence rates of CTS in certain occupations have been reported , little is known about its prevalence in the general population . OBJECTIVE To estimate the prevalence of CTS in a general population . DESIGN General health mail survey sent in February 1997 , inquiring about symptoms of pain , numbness , and tingling in any part of the body , followed 2 months later by clinical examination and nerve conduction testing of responders reporting symptoms in the median nerve distribution in the h and s , as well as of a sample of those not reporting these symptoms ( controls ) . SETTING A region in southern Sweden with a population of 170000 . PARTICIPANTS A sex- and age-stratified sample of 3000 subjects ( age range , 25 - 74 years ) was r and omly selected from the general population register and sent the survey , with a response rate of 83 % ( n = 2466 ; 46 % men ) . Of the symptomatic responders , 81 % underwent clinical examination . MAIN OUTCOME MEASURES Population prevalence rates , calculated as the number of symptomatic responders diagnosed on examination as having clinical ly certain CTS and /or electrophysiological median neuropathy divided by the total number of responders . RESULTS Of the 2466 responders , 354 reported pain , numbness , and /or tingling in the median nerve distribution in the h and s ( prevalence , 14.4 % ; 95 % confidence interval [ CI ] , 13.0%-15.8 % ) . On clinical examination , 94 symptomatic subjects were diagnosed as having clinical ly certain CTS ( prevalence , 3.8 % ; 95 % CI , 3.1%-4.6 % ) . Nerve conduction testing showed median neuropathy at the carpal tunnel in 120 symptomatic subjects ( prevalence , 4.9 % ; 95 % CI , 4.1%-5.8 % ) . Sixty-six symptomatic subjects had clinical ly and electrophysiologically confirmed CTS ( prevalence , 2.7 % ; 95 % CI , 2.1%-3.4 % ) . Of 125 control subjects clinical ly examined , electrophysiological median neuropathy was found in 23 ( 18.4 % ; 95 % CI , 12.0%-26.3 % ) . CONCLUSION Symptoms of pain , numbness , and tingling in the h and s are common in the general population . Based on our data , 1 in 5 symptomatic subjects would be expected to have CTS based on clinical examination and electrophysiologic testing ", "Abstract Objectives : To investigate in patients with repetitive strain injury ( RSI ) and in office workers using computer keyboard equipment ( a ) whether the vibration threshold in the h and was altered , ( b ) the immediate effects of keyboard use on vibration thresholds and ( c ) whether the tolerance of suprathreshold vibration was normal . Method : A vibrametre ( Somedic Ab , Stockholm Sweden ) was used to obtain threshold vibration measurements , by the method of limits , for all peripheral-nerve cutaneous distributions in the h and . Tolerance of suprathreshold stimulation was obtained by stimulation of the soft tissues of the forearm by increasing the amplitude of vibration . Results : Thresholds for vibration were significantly raised for the median nerve in both the patient and office-worker groups . The patient group additionally had raised thresholds for the ulnar nerve . Following use of the keyboard , thresholds for the median nerve were further elevated in the patient group , but not in the other groups , demonstrating a work-related exacerbation . At suprathreshold stimulation , 14 members ( 82 % ) of the patient group experienced an allodynic response to vibration , indicating possible changes in the central processing of non-noxious sensory information . This changed sensory response was not seen in either the office-worker or control groups . Conclusion : Patients may have a minor polyneuropathy , whereas the office workers demonstrate early signs of the condition . Quantitative measurement of vibration perception may prove useful in patient assessment and for detection of the early onset of RSI in the work environment", "Carpal Tunnel Syndrome ( CTS ) is an important problem among computer professionals . Hence the prevalence of CTS among computer professionals and risk factors were studied . 648 subjects were selected from 4,276 computer professionals from 21 companies with a simple r and om sampling method . CTS was diagnosed based on clinical features . The prevalence of CTS was found to be 13.1 % ( 95 % CI 10.5–15.7 % ) . Subjects with over 8 years of computer work , over 12 hrs of work per day and system administrators were at a higher risk for CTS ( OR 3.3 , 4.9 and 2.5 respectively ) . Flexed or extended h and position had higher risk for CTS . Higher risk for CTS was found with higher exposure to computer work . Ergonomic considerations are important in facilitating proper positioning of h and while working with a computer . Further studies on CTS risk factors among computer professionals are essential for planning prevention", "To study the prevalence of carpal tunnel syndrome ( CTS ) in the general population and the value of brachialgia paraesthetica nocturna ( BPN ) in diagnosing CTS , an age and sex stratified r and om sample of 715 subjects was taken from the population register of Maastricht ( The Netherl and s ) and surrounding villages , between September 1983 and July 1985 . The response rate was 70 % . Of these , 12 CTS cases had already been diagnosed . Of the remaining subjects , 64 ( 13 men , 51 women ) woke up because of BPN . Among these subjects 1 man and 23 women were found to have CTS . The prevalence rate of undetected CTS was 5.8 % [ 95 % confidence interval ( CI ) : 3.5 - 8.1 % ] in adult women ; 3.4 percent ( 95 % CI : 1.5 - 5.3 % ) had already been diagnosed as CTS . The overall prevalence rate for men was 0.6 % ( 95 % CI 0.02 - 3.4 % ) . These figures have to be regarded as minimal estimates . The overall diagnostic value of BPN for CTS was 38 % , while for women only this was 45 % ( 95 % CI : 31 - 60 % )", "The objective of this study was to examine the relationship between upper limb symptoms and keyboard use in a population survey . A question naire was mailed to 21,201 subjects aged 16 - 64 years , selected at r and om from the registers of 34 British general practice s. Information was collected on occupation and on regular use of keyboards ( for > 4 h in an average working day ) , pain in the upper limbs and neck , numbness or tingling in the upper limbs , headaches , and feelings of tiredness or stress . Associations were explored by logistic regression , with the result ant odds ratios converted into prevalence ratios ( PRs ) . Among 12,262 respondents , 4899 held non-manual occupations . These included 1871 regular users of keyboards ( e.g. computer operators , data processors , clerks , administrators , secretaries and typists ) . Pain in the neck or upper limbs and sensory symptoms were common in the non-manual workers overall ( with 1 week period prevalences of 30 and 15 % , respectively ) , and were associated with older age , smoking , headaches and tiredness or stress . After adjustment for these factors , regular keyboard use was significantly associated with pain in the past week in the shoulders ( PRs 1.2 - 1.4 ) and the wrists or h and s ( PR 1.4 ) , but not with elbow pain or sensory symptoms over the same period , or with neck or upper limb pain that prevented normal activities in the past year . Disabling symptoms were somewhat less prevalent among symptomatic keyboard users than among other symptomatic workers . We conclude that use of keyboards was associated with discomfort at the shoulder and wrist or h and , but risk estimates were lower than generally reported in workplace surveys . Previous estimates of risk in the occupational setting may have been biased by shared expectations , concerns , or other aspects of illness behaviour" ]	41189ffa-06ff-11f0-808a-c43d1ab1c353
Objective To assess the effect of different food sources of fructose‐containing sugars on glycaemic control at different levels of energy control . Design Systematic review and meta‐ analysis of controlled intervention studies . Data sources Medine , Embase , and the Cochrane Library up to 25 April 2018 . Eligibility criteria for selecting studies Controlled intervention studies of at least seven days ’ duration and assessing the effect of different food sources of fructose‐containing sugars on glycaemic control in people with and without diabetes were included . Four study design s were prespecified on the basis of energy control : substitution studies ( sugars in energy matched comparisons with other macronutrients ) , addition studies ( excess energy from sugars added to diets ) , subtraction studies ( energy from sugars subtracted from diets ) , and ad libitum studies ( sugars freely replaced by other macronutrients without control for energy ) . Outcomes were glycated haemoglobin ( HbA1c ) , fasting blood glucose , and fasting blood glucose insulin . Data extraction and synthesis Four independent review ers extracted relevant data and assessed risk of bias . Data were pooled by r and om effects models and overall certainty of the evidence assessed by the GRADE approach ( grading of recommendations assessment , development , and evaluation ) . Results 155 study comparisons ( n=5086 ) were included . Total fructose‐containing sugars had no harmful effect on any outcome in substitution or subtraction studies , with a decrease seen in HbA1c in substitution studies ( mean difference −0.22 % ( 95 % confidence interval to −0.35 % to −0.08 % ) , −25.9 mmol/mol ( −27.3 to −24.4 ) ) , but a harmful effect was seen on fasting insulin in addition studies ( 4.68 pmol/L ( 1.40 to 7.96 ) ) and ad libitum studies ( 7.24 pmol/L ( 0.47 to 14.00 ) ) . There was interaction by food source , with specific food sources showing beneficial effects ( fruit and fruit juice ) or harmful effects ( sweetened milk and mixed sources ) in substitution studies and harmful effects ( sugars‐sweetened beverages and fruit juice ) in addition studies on at least one outcome . Most of the evidence was low quality . Conclusions Energy control and food source appear to mediate the effect of fructose‐containing sugars on glycaemic control . Although most food sources of these sugars ( especially fruit ) do not have a harmful effect in energy matched substitutions with other macronutrients , several food sources of fructose‐containing sugars ( especially sugars‐sweetened beverages ) adding excess energy to diets have harmful effects . However , certainty in these estimates is low , and more high quality r and omised controlled trials are needed . Study registration Clinical trials.gov ( NCT02716870 )	[ "A study was made of the effect of high or low intake of sucrose for periods of 14 days in a group of nineteen apparently healthy men . The high sucrose diet produced no change in blood levels of cholesterol or phospholipids , or in glucose tolerance , but it produced a significant rise in triglycerides in all nineteen men . In six of them , there was in addition a rise in serum immunoreactive insulin , especially during the glucose tolerance test , and these same six subjects also showed a considerable increase in weight and a significant increase in platelet adhesiveness . There was no difference between the six subjects and the remaining thirteen in any of the other measurements , or in the diets they consumed during the experiment . The changes produced by sucrose had disappeared , or nearly so , after 14 days of normal diet . It is suggested that the effect of sucrose in producing hyperinsulinism may be more relevant to its possible role in the aetiology of ischaemic heart disease than its effect on blood lipids . It is further suggested that only some individuals are susceptible to the development of ischaemic heart disease by dietary sucrose , and that these may be identified as those that show ‘ sucrose-induced hyperinsulinism ’", "BACKGROUND This study assessed if walking at a self-selected pace could improve postpr and ial glucose and insulin concentrations in obese adolescents consuming high-fructose ( HF ) or high-glucose ( HG ) diets . METHODS Seven obese male and female adolescents ( 18 ± 1 yr ) performed 4 , 15-day trials in a r and om order , including 1 ) HF-diet ( 50 g fructose/d added to normal diet ) while being sedentary , 2 ) HG-diet ( 50 g glucose/d ) while sedentary , 3 ) HF-diet with additional walking , and 4 ) HG-diet with additional walking . On the 15th day of each trial , the participants performed mixed meal testing in the laboratory in which they consumed three liquid shakes ( either HF or HG ) and during the HF and HG sedentary trials , the participants took did not alter postpr and ial glucose concentrations . Although walking reduced insulin secretion by 34 % and 25 % during the HF- and HG-diet , respectively ( P .05 ) , total insulin concentrations were only significantly reduced ( P > .05 ) with walking during the HF trial , possibly because walking enhanced insulin clearance to a greater extent during the HF-diet . CONCLUSIONS Walking reduces postpr and ial insulin secretion in obese adolescents consuming a high-fructose or high-glucose diet", "BACKGROUND & AIMS Diets high in fructose have been proposed to contribute to nonalcoholic fatty liver disease . We compared the effects of high-fructose and matched glucose intake on hepatic triacylglycerol ( TAG ) concentration and other liver parameters . DESIGN In a double-blind study , we r and omly assigned 32 healthy but central ly overweight men to groups that received either a high-fructose or high-glucose diet ( 25 % energy ) . These diets were provided during an initial isocaloric period of 2 weeks , followed by a 6-week washout period , and then again during a hypercaloric 2-week period . The primary outcome measure was hepatic level of TAG , with additional assessment s of TAG levels in serum and soleus muscle , hepatic levels of adenosine triphosphate , and systemic and hepatic insulin resistance . RESULTS During the isocaloric period of the study , both groups had stable body weights and concentrations of TAG in liver , serum , and soleus muscle . The high-fructose diet produced an increase of 22 ± 52 μmol/L in the serum level of uric acid , whereas the high-glucose diet led to a reduction of 23 ± 25 μmol/L ( P high-fructose diet also produced an increase of 0.8 ± 0.9 in the homeostasis model assessment of insulin resistance , whereas the high-glucose diet produced an increase of only 0.1 ± 0.7 ( P = .03 ) . During the hypercaloric period , participants in the high-fructose and high-glucose groups had similar increases in weight ( 1.0 ± 1.4 vs 0.6 ± 1.0 kg ; P = .29 ) and absolute concentration of TAG in liver ( 1.70 % ± 2.6 % vs 2.05 % ± 2.9 % ; P = .73 ) and serum ( 0.36 ± 0.75 vs 0.33 ± 0.38 mmol/L ; P = .91 ) , and similar results in biochemical assays of liver function . Body weight changes were associated with changes in liver biochemistry and concentration of TAGs . CONCLUSIONS In the isocaloric period , overweight men who were on a high-fructose or a high-glucose diet did not develop any significant changes in hepatic concentration of TAGs or serum levels of liver enzymes . However , in the hypercaloric period , both high-fructose and high-glucose diets produced significant increases in these parameters without any significant difference between the 2 groups . This indicates an energy-mediated , rather than a specific macronutrient-mediated , effect . Clinical trials.gov no : NCT01050140", "Background Raisins are a significant source of dietary fiber and polyphenols , which may reduce cardiovascular disease ( CVD ) risk by affecting lipoprotein metabolism and inflammation . Walking represents a low intensity exercise intervention that may also reduce CVD risk . The purpose of this study was to determine the effects of consuming raisins , increasing steps walked , or a combination of these interventions on blood pressure , plasma lipids , glucose , insulin and inflammatory cytokines . Results Thirty-four men and postmenopausal women were matched for weight and gender and r and omly assigned to consume 1 cup raisins/d ( RAISIN ) , increase the amount of steps walked/d ( WALK ) or a combination of both interventions ( RAISINS + WALK ) . The subjects completed a 2 wk run-in period , followed by a 6 wk intervention . Systolic blood pressure was reduced for all subjects ( P = 0.008 ) . Plasma total cholesterol was decreased by 9.4 % for all subjects ( P in plasma LDL cholesterol ( LDL-C ) ( P were decreased by 19.5 % for WALK ( P effect ) . Plasma TNF-α was decreased from 3.5 ng/L to 2.1 ng/L for RAISIN ( P reduction in plasma sICAM-1 ( P adding raisins to the diet or increasing steps walked have distinct beneficial effects on CVD risk", "Nonalcoholic fatty liver disease ( NAFLD ) is now thought to be the most common liver disease worldwide . Cardiovascular complications are a leading cause of mortality in NAFLD . Fructose , a common nutrient in the westernized diet , has been reported to be associated with increased cardiovascular risk , but its impact on adolescents with NAFLD is not well understood . We design ed a 4-week r and omized , controlled , double-blinded beverage intervention study . Twenty-four overweight Hispanic-American adolescents who had hepatic fat > 8 % on imaging and who were regular consumers of sweet beverages were enrolled and r and omized to calorie-matched study -provided fructose only or glucose only beverages . After 4 weeks , there was no significant change in hepatic fat or body weight in either group . In the glucose beverage group there was significantly improved adipose insulin sensitivity , high sensitivity C-reactive protein ( hs-CRP ) , and low-density lipoprotein ( LDL ) oxidation . These findings demonstrate that reduction of fructose improves several important factors related to cardiovascular disease despite a lack of measurable improvement in hepatic steatosis . Reducing dietary fructose may be an effective intervention to blunt atherosclerosis progression among NAFLD patients and should be evaluated in longer term clinical trials", "OBJECTIVE Assumptions have linked orange juice ( OJ ) consumption with weight gain and adverse effects on health due to its sugar content ; however , epidemiologic studies have not shown increased risk for overweight or obesity with the consumption of 100 % OJ . The aim of this study was to verify whether the combination of a reduced-calorie diet ( RCD ) and 100 % OJ contribute to weight loss , promote changes in glucose and lipid metabolism , and improve diet quality in obese individuals . METHODS A r and omized controlled trial with 78 obese patients ( age 36 ± 1 y , body mass index [ BMI ] 33 ± 3 kg/m2 ) were enrolled in two groups : Individuals in the OJ group su bmi tted to an RCD that included OJ ( 500 mL/d ) , and individuals in the control group su bmi tted to an RCD without OJ . Body composition , biochemical biomarkers , and dietary intake were analyzed over a 12-wk period . RESULTS Both treatments had similar outcomes regarding body weight ( -6.5 kg ; P = 0.363 ) , BMI ( -2.5 kg/m2 ; P = 0.34 ) , lean mass ( -1 kg ; P = 0.29 ) , fat mass ( -5 kg ; P = 0.58 ) , body fat ( -3 % ; P = 0.15 ) , and waist-to-hip ratio ( -0.1 ; P = 0.79 ) . Insulin levels in the OJ group decreased by 18 % ( P = 0.05 ) , homeostasis model assessment -insulin resistance by 33 % ( P = 0.04 ) , total cholesterol by 24 % ( P = 0.004 ) , low-density lipoprotein cholesterol by 24 % ( P ≤ 0.001 ) , and high-sensitivity C-reactive protein levels by 33 % ( P = 0.001 ) compared with the control group . Consumption of energy and nutrients was similar between the two groups , but vitamin C and folate increased by 62 % ( P ≤ 0.015 ) and 39 % ( P = 0.033 ) , respectively , after OJ intervention . CONCLUSION When consumed concomitantly with an RCD , OJ does not inhibit weight loss ; ameliorate the insulin sensitivity , lipid profile , or inflammatory status , or contribute nutritionally to the quality of the diet", "We have studied whether the sucrose-induced reduction of insulin sensitivity and cellular insulin binding in normal man is related to the fructose or the glucose moiety . Seven young healthy subjects were fed their usual diets plus 1000 kcal extra glucose per day and eight young healthy subjects were fed their usual diets with addition of 1000 kcal extra fructose per day . The dietary regimens continued for 1 week . Before change of diet there were no statistically significant differences between body weight and fasting plasma concentrations of glucose , insulin , and ketone bodies in the two groups studied . High-glucose feeding caused no significant changes in insulin binding or insulin sensitivity whereas high-fructose feeding was accompanied by a significant reduction both of insulin binding ( P less than 0.05 ) and insulin sensitivity ( P less than 0.05 ) . The changes in insulin binding and insulin sensitivity correlated linearly ( r = 0.52 , P less than 0.01 ) . We conclude that fructose seems to be responsible for the impaired insulin binding and insulin sensitivity induced by sucrose", " Ten hyperinsulinemic and 11 nonhyperinsulinemic men consumed a typical American diet containing 20 % of calories either as fructose or as high-amylose cornstarch for 5 wk in a crossover design to determine their effects on indices of glucose tolerance . Blood glucose , insulin , and fructose were determined before and 30 , 60 , 90 , 120 and 180 min after breakfast , lunch , and dinner . Glucose responses were significantly lower 60 and 120 min and the insulin response lower 60 min after the meals containing fructose . Hyperinsulinemic men showed a tendency toward decreased insulin sensitivity after consuming fructose on the basis of an increased insulin-to-glucose ratio and decreased insulin binding to erythrocytes . These results generally show a beneficial effect of fructose on glucose tolerance ; however , recommendations for including large amounts of fructose in the diet should also be based on a complete evaluation of the effect on other metabolic risk factors", "BACKGROUND About 9 % of average dietary energy intake in the United States comes from fructose . Such a high consumption raises concern about the metabolic effects of this sugar . OBJECTIVE The objective of this study was to determine the effect of dietary fructose on plasma lipids . DESIGN The study was conducted in the General Clinical Research Center at Fairview-University of Minnesota Medical Center . The participants were 24 healthy adult volunteers ( 12 men and 12 women ; 6 of each sex were aged /=40 y ) . All subjects received 2 isoenergetic study diets assigned by using a r and omized , balanced crossover design . One diet provided 17 % of energy as fructose . The other diet was sweetened with glucose and was nearly devoid of fructose . Each diet was fed for 6 wk . Both diets were composed of common foods and contained nearly identical amounts of carbohydrate , protein , fat , fiber , cholesterol , and saturated , monounsaturated , and polyunsaturated fatty acids . All meals were prepared in the metabolic kitchen of the General Clinical Research Center . RESULTS The responses to the study diets differed by sex . In men , the fructose diet produced significantly higher fasting , postpr and ial , and daylong plasma triacylglycerol concentrations than did the glucose diet . The daylong plasma triacylglycerol concentration after 6 wk of the fructose diet was 32 % greater in men than the corresponding concentration during the glucose diet ( P : fructose diet had no significant effect on fasting or postpr and ial plasma triacylglycerol concentrations in women . The fructose diet also had no persistent effect on fasting plasma cholesterol , HDL cholesterol , or LDL cholesterol in either men or women . CONCLUSIONS Dietary fructose was associated with increased fasting and postpr and ial plasma triacylglycerol concentrations in men . Diets high in added fructose may be undesirable , particularly for men . Glucose may be a suitable replacement sugar", "BACKGROUND Dietary patterns characterized by high intakes of fruits and vegetables , whole grains , low-fat dairy products , and low glycemic load have been associated with lower type 2 diabetes mellitus ( T2DM ) risk . In contrast , dietary patterns that include high intakes of refined grains , processed meats , and high amounts of added sugars have been associated with increased T2DM risk . OBJECTIVE This r and omized , 2-period crossover trial compared the effects of dairy and sugar-sweetened product ( SSP ) consumption on insulin sensitivity and pancreatic β-cell function in men and women at risk of the development of T2DM who habitually consume sugar-sweetened beverages . METHODS In a r and omized , controlled crossover trial , participants consumed dairy products ( 474 mL/d 2 % milk and 170 g/d low-fat yogurt ) and SSPs ( 710 mL/d nondiet soda and 108 g/d nondairy pudding ) , each for 6 wk , with a 2-wk washout between treatments . A liquid meal tolerance test ( LMTT ) was administered at baseline and the end of each period . RESULTS Participants were 50 % female with a mean age and body mass index of 53.8 y and 32.2 kg/m(2 ) , respectively . Changes from baseline were significantly different between dairy product and SSP conditions for median homeostasis model assessment 2-insulin sensitivity ( HOMA2-%S ) ( 1.3 vs. -21.3 % , respectively , P = 0.009 ; baseline = 118 % ) , mean LMTT disposition index ( -0.03 vs. -0.36 , respectively , P = 0.011 ; baseline = 2.59 ) , mean HDL cholesterol ( 0.8 vs. -4.2 % , respectively , P = 0.015 ; baseline = 44.3 mg/dL ) , and mean serum 25-hydroxyvitamin D [ 25(OH)D ] ( 11.7 vs. -3.3 , respectively , P = 0.022 ; baseline = 24.5 μg/L ) . Changes from baseline in LMTT Matsuda insulin sensitivity index ( -0.10 vs. -0.49 , respectively ; baseline = 4.16 ) and mean HOMA2-β-cell function ( -2.0 vs. 5.3 % , respectively ; baseline = 72.6 % ) did not differ significantly between treatments . CONCLUSION These results suggest that SSP consumption is associated with less favorable values for HOMA2-%S , LMTT disposition index , HDL cholesterol , and serum 25(OH)D in men and women at risk of T2DM vs. baseline values and values during dairy product consumption . This trial was registered at clinical trials.gov as NCT01936935", "OBJECTIVE To test the hypothesis that family dietary coaching would improve nutritional intakes and weight control in free-living ( noninstitutionalized ) children and parents . DESIGN R and omized controlled trial . SETTING Fifty-four elementary schools in Paris , France . PARTICIPANTS One thous and thirteen children ( mean age , 7.7 years ) and 1013 parents ( mean age , 40.5 years ) . INTERVENTION Families were r and omly assigned to group A ( advised to reduce fat and to increase complex carbohydrate intake ) , group B ( advised to reduce both fat and sugar and to increase complex carbohydrate intake ) , or a control group ( given no advice ) . Groups A and B received monthly phone counseling and Internet-based monitoring for 8 months . OUTCOME MEASURES Changes in nutritional intake , body mass index ( calculated as weight in kilograms divided by height in meters squared ) , fat mass , physical activity , blood indicators , and quality of life . RESULTS Compared with controls , participants in the intervention groups achieved their nutritional targets for fat intake and to a smaller extent for sugar and complex carbohydrate intake , leading to a decrease in energy intake ( children , P Mean changes in body mass index were similar among children ( group A , + 0.05 , 95 % confidence interval [ CI ] , - 0.06 to 0.16 ; group B , + 0.10 , 95 % CI , - 0.03 to 0.23 ; control group , + 0.13 , 95 % CI , 0.04 - 0.22 ; P = .45 ) , but differed in parents ( group A , + 0.13 , 95 % CI , - 0.01 to 0.27 ; group B , - 0.02 , 95 % CI , - 0.14 to 0.11 ; control group , + 0.24 , 95 % CI , 0.13 - 0.34 ; P = .001 ) , with a significant difference between group B and the control group ( P = .01 ) . CONCLUSIONS Family dietary coaching improves nutritional intake in free-living children and parents , with beneficial effects on weight control in parents . Trial Registration clinical trials.gov Identifier : NCT00456911", "BACKGROUND The consumption of sucrose-sweetened soft drinks ( SSSDs ) has been associated with obesity , the metabolic syndrome , and cardiovascular disorders in observational and short-term intervention studies . Too few long-term intervention studies in humans have examined the effects of soft drinks . OBJECTIVE We compared the effects of SSSDs with those of isocaloric milk and a noncaloric soft drink on changes in total fat mass and ectopic fat deposition ( in liver and muscle tissue ) . DESIGN Overweight subjects ( n = 47 ) were r and omly assigned to 4 different test drinks ( 1 L/d for 6 mo ) : SSSD ( regular cola ) , isocaloric semiskim milk , aspartame-sweetened diet cola , and water . The amount of intrahepatic fat and intramyocellular fat was measured with (1)H-magnetic resonance spectroscopy . Other endpoints were fat mass , fat distribution ( dual-energy X-ray absorptiometry and magnetic resonance imaging ) , and metabolic risk factors . RESULTS The relative changes between baseline and the end of 6-mo intervention were significantly higher in the regular cola group than in the 3 other groups for liver fat ( 132 - 143 % , sex-adjusted mean ; P skeletal muscle fat ( 117 - 221 % ; P visceral fat ( 24 - 31 % ; P blood triglycerides ( 32 % ; P total cholesterol ( 11 % ; P Total fat mass was not significantly different between the 4 beverage groups . Milk and diet cola reduced systolic blood pressure by 10 - 15 % compared with regular cola ( P diet cola had effects similar to those of water . CONCLUSION Daily intake of SSSDs for 6 mo increases ectopic fat accumulation and lipids compared with milk , diet cola , and water . Thus , daily intake of SSSDs is likely to enhance the risk of cardiovascular and metabolic diseases . This trial is registered at clinical trials.gov as NCT00777647", "Excess sugar consumption may promote adverse changes in hepatic and total body insulin resistance . Debate continues over the effects of sugars at more typically consumed levels and whether the identity of the sugar consumed is important . In the present study participants ( 20–60 years old ) were r and omly assigned to one of five groups , three that consumed low fat milk with added fructose containing sugars in amounts equivalent to the 50th percentile of fructose consumption ( US ) , one which consumed low-fat milk sweetened with glucose , and one unsweetened low-fat milk control group . The intervention lasted ten weeks . In the entire study population there was less than 1 kg increase in weight ( 73.6 ± 13.0 vs. 74.5 ± 13.3 kg , p the change in weight was comparable among groups ( p > 0.05 ) . There were no changes in fasting glucose ( 49 ± 0.4 vs. 5.0 ± 0.5 mmol/L ) , insulin ( 56.9 ± 38.9 vs. 61.8 ± 50.0 pmol/L ) , or insulin resistance , as measured by the Homeostasis Model Assessment method ( 1.8 ± 1.3 vs. 2.0 ± 1.5 , all p > 0.05 ) . These data suggest that added sugar consumed at the median American intake level does not produce changes in measures of insulin sensitivity or glucose tolerance and that no sugar has more deleterious effects than others", "To further underst and the effect of high carbohydrate (CHO)-low fat diets and the role of variations in dietary sucrose on CHO and lipid metabolism , 10 patients with hypertriglyceridemia were fed 2 isocaloric , typical American diets , containing 40 % and 60 % CHO , for 15 days in r and om sequence . Each patient was their own control , and they were divided into 2 groups of 5 patients each . In one group , sucrose was held constant at 13 % of total calories ( 40 - 13 % and 60 - 13 % ) , whereas the sucrose content was 9 % of the total calories on a 40 % CHO diet ( 40 - 9 % ) , and 15 % of total calories on a 60 % CHO diet ( 60 - 15 % ) in the other group . Fasting and postpr and ial blood sample s were analyzed for plasma glucose , insulin , cholesterol ( Chol ) , and triglycerides ( TG ) , as well as for Chol and TG in chylomicrons , very low density , low density , and high density lipoproteins ( HDL ) . Fasting plasma TG levels were significantly increased in both groups on the 60 % CHO diet , primarily due to increases in very low density-TG concentration . The magnitude of the elevation was attenuated when sucrose content was kept constant . Postpr and ial TG responses were qualitatively similar . There were no significant changes in plasma Chol concentrations , except for a modest fall in plasma HDL-Chol level after the 60 - 13 % diet period ( P less than 0.05 ) . No significant differences were found in fasting plasma glucose or insulin concentration . However , postpr and ial glucose and insulin responses were increased on both high CHO diets . The results of these studies demonstrate that high CHO-low fat diets , in general , tend to elevate plasma glucose , insulin , and TG concentrations and reduce HDL-Chol concentration in patients with endogenous hypertriglyceridemia . In addition , these data illustrate the important role that small variations in dietary sucrose can play in modulation of CHO and lipid metabolism", "Postpr and ial concentrations of glucose , insulin and triacylglycerols ( TG ) correlate to risk for CHD . Carbohydrates affect many metabolites that could have a potential effect on cardiovascular risk factors . The objective of the present study was to examine , using a r and omised prospect i ve study , the acute ( day 1 ) and ad libitum medium-term ( day 24 ) effects of four diets : a high-fat diet ( HIGH-FAT ; 50 % fat , > 34 % monounsaturated fatty acids ) ; a low-glycaemic index ( GI ) diet ( LOW-GI ; high-carbohydrate , low-GI ) ; a high-sucrose diet ( SUCROSE ; high carbohydrate increase of 90 g sucrose/d ) ; a high-GI diet ( HIGH-GI ; high-carbohydrate , high-GI ) . Daytime profiles ( 8 h ) ( breakfast , lunch and tea ) of lipid and carbohydrate metabolism were completed during day 1 and day 24 . Seventeen middle-aged men with one or more cardiac risk factors completed the study . There was no change from day 1 or between diets in fasting glucose , lipids or homeostatic assessment model ( HOMA ) on day 24 . The HIGH-FAT compared with the three high-carbohydrate diets was associated with lower postpr and ial insulin and glucose but higher postpr and ial TG and non-esterified fatty acids ( NEFA ) . There was a significant increase in the 6 h ( 15.00 hours ) TG concentration ( day 1 , 2.6 ( sem 0.3 ) mmol/l v. day 24 , 3.3 ( sem 0.3 ) mmol/l ; P Postpr and ial HOMA ( i.e. incremental area under the curve ( IAUC ) glucose ( mmol/l per min)xIAUC insulin/22.5 ( mU/l per min ) ) median changes from day 1 to day 24 were -61 , -43 , -20 and + 31 % for the HIGH-FAT , LOW-GI , SUCROSE and HIGH-GI diets respectively . The HIGH-GI percentage change was significantly different from the other three diets ( P SUCROSE diet ( + 0.84 ( sem 0.3 ) kg ) . In conclusion the HIGH-FAT diet had a beneficial effect on postpr and ial glucose and insulin over time but it was associated with higher postpr and ial concentrations of TG and NEFA . Conversely the HIGH-GI diet appeared to increase postpr and ial insulin resistance over the study period", "Abstract Just as the type and duration of physical activity can have variable effects on the glucose levels and other cardiometabolic parameters among patients with type 2 diabetes mellitus ( T2DM ) , so can the types of foods have variable effects as well . This 12-week r and omized study of 51 study participants evaluated the impact of routine consumption of dark raisins versus alternative processed snacks on glucose levels and other cardiovascular risk factors among patients with type T2DM . In this study , compared to alternative processed snacks , those who consumed raisins had a significant 23 % reduction in postpr and ial glucose levels ( P = 0.024 ) . Also compared to snacks , those who consumed raisins had a 19 % reduction in fasting glucose and 0.12 % reduction in hemoglobin A1c , although these latter findings did not achieve statistical significance . Regarding blood pressure , compared to alternative processed snacks , those who consumed raisins had a significant 8.7 mmHg reduction in systolic blood pressure ( P = 0.035 ) ( 7.5 % [ P = 0.031 ] ) but did not experience a significant reduction in diastolic blood pressure . Compared to alternative processed snacks , those who consumed raisins did not have a significant improvement in body weight , body mass index , waist circumference , fasting insulin , homeostatic model assessment of insulin resistance , total cholesterol , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol ( HDL ) , triglyceride , or non-HDL cholesterol levels . Overall , these data support raisins as a healthy alternative compare to processed snacks in patients with T2DM", "Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more", "Purpose Consumption of sugar-reformulated products ( commercially available foods and beverages that have been reduced in sugar content through reformulation ) is a potential strategy for lowering sugar intake at a population level . The impact of sugar-reformulated products on body weight , energy balance ( EB ) dynamics and cardiovascular disease risk indicators has yet to be established . The REFORMulated foods ( REFORM ) study examined the impact of an 8-week sugar-reformulated product exchange on body weight , EB dynamics , blood pressure , arterial stiffness , glycemia and lipemia . Methods A r and omized , controlled , double-blind , crossover dietary intervention study was performed with fifty healthy normal to overweight men and women ( age 32.0 ± 9.8 year , BMI 23.5 ± 3.0 kg/m2 ) who were r and omly assigned to consume either regular sugar or sugar-reduced foods and beverages for 8 weeks , separated by 4-week washout period . Body weight , energy intake ( EI ) , energy expenditure and vascular markers were assessed at baseline and after both interventions . Results We found that carbohydrate ( P total sugars ( P extrinsic sugars ( P 0.001 ) ( % EI ) were lower , whereas fat ( P = 0.001 ) and protein ( P = 0.038 ) intakes ( % EI ) were higher on the sugar-reduced than the regular diet . No effects on body weight , blood pressure , arterial stiffness , fasting glycemia or lipemia were observed . Conclusions Consumption of sugar-reduced products , as part of a blinded dietary exchange for an 8-week period , result ed in a significant reduction in sugar intake . Body weight did not change significantly , which we propose was due to energy compensation", "OBJECTIVE To test the hypothesis that substituting artificially sweetened beverages ( ASB ) for sugar-sweetened beverages ( SSB ) decreases intrahepatocellular lipid concentrations ( IHCL ) in overweight subjects with high SSB consumption . METHODS About 31 healthy subjects with BMI greater than 25 kg/m(2 ) and a daily consumption of at least 660 ml SSB were r and omized to a 12-week intervention in which they replaced SSBs with ASBs . Their IHCL ( magnetic resonance spectroscopy ) , visceral adipose tissue volume ( VAT ; magnetic resonance imaging ) , food intake ( 2-day food records ) , and fasting blood concentrations of metabolic markers were measured after a 4-week run-in period and after a 12-week period with ASB or control ( CTRL ) . RESULTS About 27 subjects completed the study . IHCL was reduced to 74 % of the initial values with ASB ( N = 14 ; P IHCL attained with ASB was more important in subjects with IHCL greater than 60 mmol/l than in subjects with low IHCL . ALT decreased significantly with SSB only in subjects with IHCL greater than 60 mmol/l . There was otherwise no significant effect of ASB on body weight , VAT , or metabolic markers . CONCLUSIONS In subjects with overweight or obesity and a high SSB intake , replacing SSB with ASB decreased intrahepatic fat over a 12-week period", "American children consume up to 27 % of calories from high-fat and high-sugar snacks . Both sugar and fat consumption have been implicated as a cause of hepatic steatosis and obesity but the effect of meal pattern is largely understudied . We hypothesized that a high meal frequency , compared to consuming large meals , is detrimental in the accumulation of intrahepatic and abdominal fat . To test this hypothesis , we r and omized 36 lean , healthy men to a 40 % hypercaloric diet for 6 weeks or a eucaloric control diet and measured intrahepatic triglyceride content ( IHTG ) using proton magnetic resonance spectroscopy ( 1H-MRS ) , abdominal fat using magnetic resonance imaging ( MRI ) , and insulin sensitivity using a hyperinsulinemic euglycemic clamp with a glucose isotope tracer before and after the diet intervention . The caloric surplus consisted of fat and sugar ( high-fat-high-sugar ; HFHS ) or sugar only ( high-sugar ; HS ) and was consumed together with , or between , the three main meals , thereby increasing meal size or meal frequency . All hypercaloric diets similarly increased body mass index ( BMI ) . Increasing meal frequency significantly increased IHTG ( HFHS mean relative increase of 45 % ; P = 0.016 and HS mean relative increase of 110 % ; P = 0.047 ) , whereas increasing meal size did not ( 2-way analysis of variance [ ANOVA ] size versus frequency P = 0.03 ) . Abdominal fat increased in the HFHS-frequency group ( + 63.3 ± 42.8 mL ; P = 0.004 ) and tended to increase in the HS-frequency group ( + 46.5 ± 50.7 mL ; P = 0.08 ) . Hepatic insulin sensitivity tended to decrease in the HFHS-frequency group while peripheral insulin sensitivity was not affected . Conclusion : A hypercaloric diet with high meal frequency increased IHTG and abdominal fat independent of caloric content and body weight gain , whereas increasing meal size did not . This study suggests that snacking , a common feature in the Western diet , independently contributes to hepatic steatosis and obesity . ( Trial registration : http://www.forestplots.net ; nr . NCT01297738 . ) ( Hepatology 2014;60:545–553", "BACKGROUND Honey has been shown to have beneficial effects on the glucose and lipid profiles in patients at high risk of heart diseases . Therefore , this study was carried out to investigate the effects of natural honey on blood glucose and lipid profile in healthy individuals . METHODS A r and omized controlled trial was carried out in the Army Medical College , Rawalpindi , Pakistan , spanning 4 weeks , that is , from 15th Feb-15th March 2009 . A total of 70 healthy young boarders of the same college were included in the study and r and omly divided into two groups of 35 each using r and om number table . Seventy gram ( 70 g ) of honey was given to each individual in the experimental group daily for a period of 4 weeks while control group was kept on the same diet as that of experimental group except honey . The fasting glucose , total cholesterol , low density lipoprotein ( LDL ) , high density lipoprotein ( HDL ) and triglyceride ( TG ) levels were measured before and after the experiment . RESULTS The fasting glucose levels in both groups were raised . However , the increase in the experimental group was significantly less than that in the control group ( p levels of total cholesterol , LDL and triglycerides in the control group increased while those in the experiment group decreased significantly ( p HDL levels were decreased in the former and increased in the latter group ( p Natural honey consumption significantly limits the rise in blood glucose along with a significant decrease in the levels of total cholesterol , LDL and triglycerides , and increase HDL in young healthy adults", "Abstract Purpose To compare the effects of three ready-to-eat mixed meals , with a high fiber content and low glycemic index , on postpr and ial glycemic and insulinemic response in patients with Type 2 diabetes mellitus ( T2DM ) . Methods The current study followed a prospect i ve , three-way , cross-over design . Twenty-four patients with T2DM consumed three ready-to-eat mixed meals , i.e. , “ wild greens pie ” ( meal 1 ) , “ chicken burgers with boiled vegetables ” ( meal 2 ) and “ vegetable moussaka ” ( meal 3 ) and an oral glucose load , all providing 50 g of carbohydrates . Venous blood was collected at 0 , 30 , 60 , 90 and 120 min postpr and ial . Statistical analyses included repeated measures analysis of variance and calculations of the area under the glucose and insulin curves ( AUC ) for each one of the test meals and the oral glucose load . Results Patients consuming each one of the three mixed meals showed better postpr and ial glycemic responses compared to the oral glucose load ( P insulinemic response compared to the oral glucose load and meal 1 , after 60 and 120 min postpr and ial , respectively ( P HOMA-IR values from T0 to T120 was significantly lower for meal 3 , compared to the oral glucose load ( P mixed meals examined in the present study were found to elicit significantly lower glycemic responses compared to the oral glucose load in diabetic patients . The mixed meals examined in the present study could be proposed as effective , palatable and practical solutions for diabetics for glucose control", "OBJECTIVE To investigate the long-term effects of changes in dietary carbohydrate/fat ratio and simple vs complex carbohydrates . DESIGN R and omized controlled multicentre trial ( CARMEN ) , in which subjects were allocated for 6 months either to a seasonal control group ( no intervention ) or to one of three experimental groups : a control diet group ( dietary intervention typical of the average national intake ) ; a low-fat high simple carbohydrate group ; or a low-fat high complex carbohydrate group . SUBJECTS Three hundred and ninety eight moderately obese adults . MEASUREMENTS The change in body weight was the primary outcome ; changes in body composition and blood lipids were secondary outcomes . RESULTS Body weight loss in the low-fat high simple carbohydrate and low-fat high complex carbohydrate groups was 0.9 kg ( P control diet and seasonal control groups gained weight ( 0.8 and 0.1 kg , NS ) . Fat mass changed by -1.3 kg ( P Changes in blood lipids did not differ significantly between the dietary treatment groups . CONCLUSION Our findings suggest that reduction of fat intake results in a modest but significant reduction in body weight and body fatness . The concomitant increase in either simple or complex carbohydrates did not indicate significant differences in weight change . No adverse effects on blood lipids were observed . These findings underline the importance of this dietary change and its potential impact on the public health implication s of obesity", "OBJECTIVE We investigated the effect of fruit intake on body weight change . METHODS Hypercholesterolemic , overweight ( body mass index > 25 kg/m2 ) , and non-smoking women , 30 to 50 y of age , were r and omized to receive , free of charge , one of three dietary supplements : apples , pears , or oat cookies . Women were instructed to eat one supplement three times a day in a total of six meals a day . Participants ( 411 women ) were recruited at a primary care center of the State University of Rio de Janeiro , Brazil . Fifty-one women had fasting blood cholesterol levels greater than 6.2 mM/L ( 240 mg/dL ) and 49 were r and omized . Subjects were instructed by a dietitian to eat a diet ( 55 % of energy from carbohydrate , 15 % from protein , and 30 % from fat ) to encourage weight reduction at the rate of 1 kg/mo . RESULTS After 12 wk of follow-up , the fruit group lost 1.22 kg ( 95 % confidence interval = 0.44 - 1.85 ) , whereas the oat group had a non-significant weight loss of 0.88 kg ( 0.37 - 2.13 ) . The difference between the two groups was statistically significant ( P = 0.004 ) . To explore further the body weight loss associated with fruit intake , we measured the ratio of glucose to insulin . A significantly greater decrease of blood glucose was observed among those who had eaten fruits compared with those who had eaten oat cookies , but the glucose : insulin ratio was not statistically different from baseline to follow-up . Adherence to the diet was high , as indicated by changes in serum triacylglycerols , total cholesterol , and reported fruit intake . Fruit intake in the oat group throughout treatment was minimal . CONCLUSIONS Intake of fruits may contribute to weight loss", "Background The importance of exchanging sucrose for artificial sweeteners on risk factors for developing diabetes and cardiovascular diseases is not yet clear . Objective To investigate the effects of a diet high in sucrose versus a diet high in artificial sweeteners on fasting and postpr and ial metabolic profiles after 10 weeks . Design Healthy overweight subjects were r and omised to consume drinks and foods sweetened with either sucrose ( ∼2 g/kg body weight ) ( n = 12 ) or artificial sweeteners ( n = 11 ) as supplements to their usual diet . Supplements were similar on the two diets and consisted of beverages ( ∼80 weight% ) and solid foods ( yoghurts , marmalade , ice cream , stewed fruits ) . The rest of the diet was free of choice and ad libitum . Before ( week 0 ) and after the intervention ( week 10 ) fasting blood sample s were drawn and in week 10 , postpr and ial blood was sample d during an 8-hour meal test ( breakfast and lunch ) . Results After 10 weeks postpr and ial glucose , insulin , lactate , triglyceride , leptin , glucagon , and GLP-1 were all significantly higher in the sucrose compared with the sweetener group . After adjusting for differences in body weight changes and fasting values ( week 10 ) , postpr and ial glucose , lactate , insulin , GIP , and GLP-1 were significantly higher and after further adjusting for differences in energy and sucrose intake , postpr and ial lactate , insulin , GIP , and GLP-1 levels were still significantly higher on the sucrose-rich diet . Conclusion A sucrose-rich diet consumed for 10 weeks result ed in significant elevations of postpr and ial glycaemia , insulinemia , and lipidemia compared to a diet rich in artificial sweeteners in slightly overweight healthy subjects", "OBJECTIVE High-heat cooking of food induces the formation of advanced glycation end products ( AGEs ) , which are thought to impair glucose metabolism in type 2 diabetic patients . High intake of fructose might additionally affect endogenous formation of AGEs . This parallel intervention study investigated whether the addition of fructose or cooking methods influencing the AGE content of food affect insulin sensitivity in overweight individuals . RESEARCH DESIGN AND METHODS Seventy-four overweight women were r and omized to follow either a high- or low-AGE diet for 4 weeks , together with consumption of either fructose or glucose drinks . Glucose and insulin concentrations — after fasting and 2 h after an oral glucose tolerance test — were measured before and after the intervention . Homeostasis model assessment of insulin resistance ( HOMA-IR ) and insulin sensitivity index were calculated . Dietary and urinary AGE concentrations were measured ( liquid chromatography t and em mass spectrometry ) to estimate AGE intake and excretion . RESULTS When adjusted for changes in anthropometric measures during the intervention , the low-AGE diet decreased urinary AGEs , fasting insulin concentrations , and HOMA-IR , compared with the high-AGE diet . Addition of fructose did not affect any outcomes . CONCLUSIONS Diets with high AGE content may increase the development of insulin resistance . AGEs can be reduced by modulation of cooking methods but is unaffected by moderate fructose intake", "Background It is unclear if the sugar intake may affect metabolic parameters in individuals with type 1 diabetes . Therefore , the purpose of this study was to evaluate the effects of sucrose intake in glycemic , lipemic , anthropometric variables , as well as in C-reactive protein ( CRP ) levels in these individuals . Methods Thirty-three subjects with type 1 diabetes were evaluated at baseline and 3-months after intervention . Volunteers were r and omized into groups : sucrose-free ( diet without sucrose ) or sucrose-added ( foods containing sucrose in composition ) . Both groups received the same macronutrient composition and used the carbohydrate counting methods . All underwent an interview and anthropometric evaluation . Blood was drawn for glycated haemoglobin , glucose , total cholesterol , HDL , and CRP measurement , and the medical charts were review ed in all cases . Results At baseline , anthropometric , clinical and laboratory variables did not differ between groups , except for the triglycerides . Although at baseline triglycerides levels were higher in the sucrose-added group ( p = 0.01 ) , they did not differ between groups after the intervention ( p = 0.92 ) . After 3-months , CRP was higher in the sucrose-added than in the sucrose-free group ( p = 0.04 ) , but no further differences were found between the groups , including the insulin requirements , anthropometric variables , body composition , and glycemic control . Both groups showed sugars intake above the recommendations at baseline and after intervention . Conclusions Sucrose intake , along with a disciplined diet , did not affect insulin requirements , anthropometric variables , body composition , lipemic and glycemic control . However , although the sucrose intakes increase CRP levels , the amount of sugar in the diet was not associated with this inflammatory marker", "The long-term impact of dietary carbohydrate type , in particular sucrose , on insulin resistance and the development of diabetes and atherosclerosis is not established . Current guidelines for the healthy population advise restriction of sucrose intake . We investigated the effect of high- versus low-sucrose diet ( 25 vs. 10 % , respectively , of total energy intake ) in 13 healthy subjects aged 33 ± 3 years ( mean ± SE ) , BMI 26.6 ± 0.9 kg/m2 , in a r and omized crossover design with sequential 6-week dietary interventions separated by a 4-week washout . Weight maintenance , eucaloric diets with identical macronutrient profiles and fiber content were design ed . All food was weighed and distributed . Insulin action was assessed using a two-step euglycemic clamp ; glycemic profiles were assessed by the continuous glucose monitoring system and vascular compliance by pulse-wave analysis . There was no change in weight across the study . Peripheral glucose uptake and suppression of endogenous glucose production were similar after each diet . Glycemic profiles and measures of vascular compliance did not change . A rise in total and LDL cholesterol was observed . In this study , a high-sucrose intake as part of an eucaloric , weight-maintaining diet had no detrimental effect on insulin sensitivity , glycemic profiles , or measures of vascular compliance in healthy nondiabetic subjects", "Background Medical nutrition therapy is recognized as an important treatment option in type 2 diabetes . Most guidelines recommend eating a diet with a high intake of fiber-rich food including fruit . This is based on the many positive effects of fruit on human health . However some health professionals have concerns that fruit intake has a negative impact on glycemic control and therefore recommend restricting the fruit intake . We found no studies addressing this important clinical question . The objective was to investigate whether an advice to reduce the intake of fruit to patients with type 2 diabetes affects HbA1c , bodyweight , waist circumference and fruit intake . Methods This was an open r and omized controlled trial with two parallel groups . The primary outcome was a change in HbA1c during 12 weeks of intervention . Participants were r and omized to one of two interventions ; medical nutrition therapy + advice to consume at least two pieces of fruit a day ( high-fruit ) or medical nutrition therapy + advice to consume no more than two pieces of fruit a day ( low-fruit ) . All participants had two consultations with a registered dietitian . Fruit intake was self-reported using 3-day fruit records and dietary recalls . All assessment s were made by the “ intention to treat ” principle . Results The study population consisted of 63 men and women with newly diagnosed type 2 diabetes . All patients completed the trial . The high-fruit group increased fruit intake with 125 grams ( CI 95 % ; 78 to 172 ) and the low-fruit group reduced intake with 51 grams ( CI 95 % ; -18 to −83 ) . HbA1c decreased in both groups with no difference between the groups ( diff . : 0.19 % , CI 95 % ; -0.23 to 0.62 ) . Both groups reduced body weight and waist circumference , however there was no difference between the groups . Conclusions A recommendation to reduce fruit intake as part of st and ard medical nutrition therapy in overweight patients with newly diagnosed type 2 diabetes result ed in eating less fruit . It had however no effect on HbA1c , weight loss or waist circumference . We recommend that the intake of fruit should not be restricted in patients with type 2 diabetes . Trial registration http://www . clinical trials.gov ; Identifier : NCT01010594", "The effect of dietary fructose ( 20 % of carbohydrate calories , 45 - 65 g day-1 for 4 weeks ) on glycaemic control , serum lipid , lipoprotein and apoprotein A-I and A-II concentrations and on insulin sensitivity was studied in 10 type 2 diabetic patients . The study was done in a r and omized , double-blind fashion with crystalline fructose or placebo administered evenly during 4 meals or snacks per day . The patients were hospitalized throughout the study periods . The fasting plasma glucose concentration decreased during the fructose ( from 10.7 + /- 1.4 mmol l-1 to 8.0 + /- 0.8 mmol l-1 , P control diet ( from 10.1 + /- 0.9 mmol l-1 to 8.0 + /- 0.7 mmol l-1 , P mean diurnal blood glucose concentration also fell both during the fructose ( from 10.8 + /- 0.5 mmol l-1 to 8.4 + /- 0.3 mmol l-1 , P HbA1 concentration improved ( P Insulin sensitivity increased by 34 % ( P Serum insulin , triglyceride , apoprotein A-I and A-II concentrations , body weight , blood pressure and blood lactate remained unchanged during both diets . In conclusion , substitution of moderate amounts of fructose for complex carbohydrates can improve glycaemic control and insulin sensitivity in patients with type 2 diabetes", "Consumption of simple carbohydrates has markedly increased over the past decades , and may be involved in the increased prevalence in metabolic diseases . Whether an increased intake of fructose is specifically related to a dysregulation of glucose and lipid metabolism remains controversial . We therefore compared the effects of hypercaloric diets enriched with fructose ( HFrD ) or glucose ( HGlcD ) in healthy men . Eleven subjects were studied in a r and omised order after 7 d of the following diets : ( 1 ) weight maintenance , control diet ; ( 2 ) HFrD ( 3.5 g fructose/kg fat-free mass ( ffm ) per d , + 35 % energy intake ) ; ( 3 ) HGlcD ( 3.5 g glucose/kg ffm per d , + 35 % energy intake ) . Fasting hepatic glucose output ( HGO ) was measured with 6,6 - 2H2-glucose . Intrahepatocellular lipids ( IHCL ) and intramyocellular lipids ( IMCL ) were measured by 1H magnetic resonance spectroscopy . Both fructose and glucose increased fasting VLDL-TAG ( HFrD : + 59 % , P IHCL ( HFrD : + 52 % , P HGO increased after both diets ( HFrD : + 5 % , P fasting glycaemia , insulin and alanine aminotransferase concentrations . IMCL increased significantly only after the HGlcD ( HFrD : + 24 % , NS ; HGlcD : + 59 % , P IHCL and VLDL-TAG were not different between hypercaloric HFrD and HGlcD , but were increased compared to values observed with a weight maintenance diet . However , glucose led to a higher increase in IMCL than fructose", "CONTEXT Consumption of high-fructose diets promotes hepatic fatty acid synthesis ( de novo lipogenesis [ DNL ] ) and an atherogenic lipid profile . It is unclear whether these effects occur independent of positive energy balance and weight gain . OBJECTIVES We compared the effects of a high-fructose , ( 25 % of energy content ) weight-maintaining diet to those of an isocaloric diet with the same macronutrient distribution but in which complex carbohydrate ( CCHO ) was substituted for fructose . DESIGN , SETTING , AND PARTICIPANTS Eight healthy men were studied as in patients for consecutive 9-day periods . Stable isotope tracers were used to measure fractional hepatic DNL and endogenous glucose production ( EGP ) and its suppression during a euglycemic-hyperinsulinemic clamp . Liver fat was measured by magnetic resonance spectroscopy . RESULTS Weight remained stable . Regardless of the order in which the diets were fed , the high-fructose diet was associated with both higher DNL ( average , 18.6 ± 1.4 % vs 11.0 ± 1.4 % for CCHO ; P = .001 ) and higher liver fat ( median , + 137 % of CCHO ; P = .016 ) in all participants . Fasting EGP and insulin-mediated glucose disposal did not differ significantly , but EGP during hyperinsulinemia was greater ( 0.60 ± 0.07 vs 0.46 ± 0.06 mg/kg/min ; P = .013 ) with the high-fructose diet , suggesting blunted suppression of EGP . CONCLUSION Short-term high-fructose intake was associated with increased DNL and liver fat in healthy men fed weight-maintaining diets", "Summary The effects of regularly eating sucrose were studied in 23 diabetic patients , 12 Type 1 ( insulin-dependent ) and 11 Type 2 ( non-insulin-dependent ) , with differing degrees of glycaemic control . Two diets , each lasting 6 weeks , were compared in a r and omised cross-over study . Both diets were high in fibre and low in fat . In one diet 45 g of complex carbohydrate was replaced by 45 g of sucrose taken at mealtimes . There were no significant biochemical differences between the two diets in either Type 1 or Type 2 patients . In Type 1 patients the mean ( ±SEM ) fasting plasma glucose was 10.5 ( 1.8 ) mmol/1 on the control diet and 10.3 ( 1.5 ) mmol/1 on sucrose . In Type 2 patients the levels were 9.1 ( 0.8 ) mmol/1 and 8.9 ( 0.8 ) mmol/l respectively . Glycosylated haemoglobin for the Type 1 patients was 9.9 % on control and 10.3 % on sucrose ; for Type 2 patients the figures were 9.3 % and 9.0 % respectively . There were no differences in mean daily plasma glucose levels or diurnal glucose profiles . Cholesterol ( total and in lipoprotein fractions ) was unchanged , as were diurnal triglyceride profiles and plasma insulin profiles in the Type 2 patients . There were no changes in medication or body weight . We conclude that a moderate amount of sucrose taken daily at mealtimes does not cause deterioration in metabolic control in diabetic patients following a high fibre/low fat diet", "Objectives We investigated the effect of natural honey on body weight and some blood biochemical indices of diabetic subjects . Methods Forty-eight diabetic type 2 patients were r and omly assigned into two groups : the honey group received oral natural honey for 8 weeks , and the control group did not take honey . Before the onset of the study ( week 0 ) and after 8 weeks , weight measurements were taken and fasting blood sample s were drawn . Results After adjustment for the baseline values , there were no significant differences in the fasting blood sugars between the two groups . Body weight , total cholesterol , low-density lipoprotein-cholesterol and triglyceride decreased ( P = 0.000 ) , and high-density lipoprotein-cholesterol increased significantly ( P levels of hemoglobin A1C increased significantly in this group ( P body weight and blood lipids of diabetic patients . However , since an increase in the hemoglobin A1C levels was observed , cautious consumption of this food by diabetic patients is recommended", "Banana is a widely consumed fruit , which contains considerable amounts of potential prebiotic indigestible carbohydrates . In our r and omised , controlled trial we aim ed to evaluate the in vivo prebiotic effect of banana consumption on faecal microbiota . Thirty-four healthy women participated in the study , having Body Mass Index ( BMI ) 24 - 30 kg/m(2 ) , age 19 - 45 years , without history of gastrointestinal disease and no antibiotic and other medication use two months prior the initiation and during the study . All women were asked to maintain their usual dietary habits for 60 days and they were r and omly assigned to consume twice a day a pre-meal snack , either one medium banana , or one cup of banana-flavoured drink or one cup of water ( control group ) . Stool sample s were collected at baseline , on days 30 and 60 of intervention for enumeration of total anaerobes , bifidobacteria and lactobacilli by plate count techniques , as well as for pH and short chain fatty acids ( SCFAs ) measurement . Gastrointestinal symptoms were also recorded . Mean bifidobacterial levels were increased only in the banana group both at 30 and 60 days of intervention , but this change did not reach a statistical significance . No significant overall differences in the total concentrations and molar ratios of SCFAs were detected according to dietary intervention . Analysis of the gastrointestinal symptoms records revealed significantly lower bloating levels in the banana group , compared to controls , at 26 - 35 days ( p = 0.009 ) and 51 - 60 days ( p = 0.010 ) . Banana consumption had also no adverse effects on evacuation patterns . We concluded that daily consumption of bananas is a well-tolerated eating behaviour , which may induce bifidogenesis in healthy women experiencing body weight problems", "Abstract Aims /hypothesisSince protein ingestion is known to stimulate the secretion of glucagon-like peptide-1 ( GLP-1 ) , we hypothesised that enhancing GLP-1 secretion to harness its insulinotropic/beta cell-stimulating activity with whey protein pre-load may have beneficial glucose-lowering effects in type 2 diabetes . Methods In a r and omised , open-label crossover clinical trial , we studied 15 individuals with well-controlled type 2 diabetes who were not taking any medications except for sulfonylurea or metformin . These participants consumed , on two separate days , 50 g whey in 250 ml water or placebo ( 250 ml water ) followed by a st and ardised high-glycaemic-index breakfast in a hospital setting . Participants were r and omised using a coin flip . The primary endpoints of the study were plasma concentrations of glucose , intact GLP-1 and insulin during the 30 min following meal ingestion . Results In each group , 15 patients were analysed . The results showed that over the whole 180 min post-meal period , glucose levels were reduced by 28 % after whey pre-load with a uniform reduction during both early and late phases . Insulin and C-peptide responses were both significantly higher ( by 105 % and 43 % , respectively ) with whey pre-load . Notably , the early insulin response was 96 % higher after whey . Similarly , both total GLP-1 ( tGLP-1 ) and intact GLP-1 ( iGLP-1 ) levels were significantly higher ( by 141 % and 298 % , respectively ) with whey pre-load . Dipeptidyl peptidase 4 plasma activity did not display any significant difference after breakfast between the groups . Conclusions /interpretationIn summary , consumption of whey protein shortly before a high-glycaemic-index breakfast increased the early pr and ial and late insulin secretion , augmented tGLP-1 and iGLP-1 responses and reduced postpr and ial glycaemia in type 2 diabetic patients . Whey protein may therefore represent a novel approach for enhancing glucose-lowering strategies in type 2 diabetes . Trial registration Clinical Trials.gov NCT01571622 Funding The Israeli Ministry of Health and Milk Council funded the research", "In order to evaluate the long term effects of a daily intake of simple sugars upon the glycemic control , 10 insulin treated diabetic out patients received , according to a r and omized cross over design , a conventional or a sucrose-enriched isocaloric , isoglucidic diet ( about 20 g sucrose per day , given as desserts and /or soft drinks during or after mixed meals ) for 3 months each . The daily insulin doses remained identical during both diets : 0.58 + /- 0.07 vs 0.58 + /- 0.06 U/kg body weight ( mean + /- SEM ) after conventional and sugar-enriched diet , respectively . The percentages of short acting insulin were also similar : 50 + /- 4 vs 49 + /- 4 % . The mean glycemic profiles after lunch and dinner were comparable with both regimens . Moreover , glycosylated hemoglobin levels were 10.0 + /- 0.3 vs 9.9 + /- 0.4 % after conventional and sucrose enriched diet , respectively . Plasma cholesterol and triglycerides remained unchanged . In conclusion , a relatively small daily intake of sucrose for 3 months has no clinical and /or metabolic side effects . Therefore , it seems no longer justified to completely ban sucrose from the diet of diabetic patients", "The consumption of specific foods in energy-restricted diets may affect the weight loss process . The purpose of this research was to evaluate whether obese women following two hypocaloric diets with distinct fruit content differ in weight loss and metabolic responses . Fifteen obese women were included , who were r and omly assigned to follow a low or a high-fruit energy-restricted diet for 8 weeks . The main outcome variables were weight and fat losses . Metabolic measurements concerning macronutrient oxidation were also assessed by using 13C labelled fructose and indirect calorimetry . The induced weight loss was similar for both diets ( 6.9 ± 2 % vs. 6.6 ± 2 % , p = 0.785 ) . Both experimental diets similarly improved the lipid plasma profile in the participants , but the cholesterol fall was higher in obese subjects receiving the diet containing more fruit . No statistical differences in lipids carbohydrates and 13C labelled fructose utilisation were observed , but protein oxidation was differently affected by the experimental diets . The compensatory effects of the associated fibre/fructose intake may explain the lack of a specific effect of the fruit amount on hypocaloric diets design ed to weight loss , although the increased fibre content from enriched fruit diets may be involved in the favourable effects on cholesterol plasma levels ", " This r and omized cross‐over study evaluates the effects of extended , guar and guar + fructose diets on the metabolic balance of children with insulin‐dependent diabetes mellitus ( IDDM ) . We studied 22 children ; mean age 12.2 years , mean duration of diabetes 4.4 years . The diet was supplemented for three weeks with guar in palatable form ( 5 % of daily carbohydrate intake ) and with guar + fructose ( 1 g of fructose/kg body weight , max 30 g/d ) for another three weeks . A control group ( 8 children , mean age 12.3 , duration of diabetes 4.3 years ) followed the same experimental protocol without guar supplementation . The metabolic balance was assessed by glucosuria index ( per cent of tests with less than 1 % glucosuria from all urine tests ) and measurements of red cell glycohaemoglobin A1c ( HbA1c ) . Serum total and HDL‐choiesterol , C‐peptide , pancreatic and enteroglucagon were also measured . HbA1c decreased during guar ( p ) and guar + fructose diet ( p The glucosuria index improved ( p and the serum total cholesterol concentration decreased ( p ) during the experimental guar diets . Guar in acceptable form and quantity in the diet appears to improve metabolic control of diabetic children", "OBJECTIVE The purpose of this study was to investigate the effect of high sucrose diet ( HD ) and high fat diet ( RFD ) ingested under free-living conditions , on insulin homeostasis , verifies the association between insulin resistance and body composition as well . RESEARCH METHODS AND PROCEDURES 20 healthy women , 13 normal-weight ( 22.5 + /- 2.1 years of age ; BMI 22.2 + /- 1.9 kg/m2 ) and 7 over-weight ( 21.8 + /- 2.8 years of age ; BMI 28.4 + /- 3.2 kg/m2 ) , included in 2 groups G1 and G2 respectively , they were r and omized to intake HD diets ( 59 % carbohydrate including 23.0 % of sucrose ; 28.0 % lipid ; 13.0 % protein ; 20.2 g fiber ) or HDF ( 42.0 % carbohydrates including 1.3 % of sucrose ; 45.0 % lipid ; 13.0 % protein ; 22.2 g fiber ) after initial assessment ( BD ) . It was taken anthropometric measures , body composition and blood sample s were obtained for fasting and post-pr and ial glucose and insulin determinations . RESULTS Glycemia , insulinemia and HOMA-IR did not differ between groups ( p > 0.05 ) . Although on BD , HOMA-IR correlates positively with weight ( r = 0.750 ) , BMI ( r = 0.929 ) , waist circumference ( WC ) ( r = 0.750 ) and percentage body fat ( r = 0.857 ) for G2 group . The values of fasting HOMA-IR on BD were significantly greater than HFD for G1 group ( p total carbohydrates amount and sucrose are greater than BD and HFD . CONCLUSION The results confirm direct correlation between HOMA-IR , abdominal obesity and body fat . Therefore diet can modulate the insulinemic action", "Aim ing at investigating the potential effect of minimal dietary changes in NAFLD patients with non-significant fibrosis , 55 patients with NAFLD were enrolled in a r and omized controlled clinical trial . Patients were assigned into two isocaloric dietary treatment groups for 24 weeks : ( a ) nutritional counseling ( Control arm , N = 27 ) , ( b ) nutritional counseling with currants included ( two fruit servings , 36 g per day ) , substituting snacks of similar caloric content ( Currant arm , N = 28 ) . Clinical tests , anthropometrics , inflammatory and oxidative stress markers were conducted pre- and post-intervention . A total of 50 patients completed the trial . Significant differences between the two arms post-intervention were observed in fasting glucose and in IL-6 levels , these being significantly decreased only in Currant patients . Body weight , BMI , HbA1c , CRP and EUS values decreased in both arms , differences being insignificant between the two arms post-intervention . Participants in the Currant arm had significantly reduced total body fat , WC and trunk fat . Ultrasound scanning improved significantly in patients snacking currants daily . Also , volunteers enrolled in the Currant arm showed a reduced intake of saturated fatty acids . Because BW regulation has been officially recognised as a treatment approach in NAFLD an additional analysis was repeated in patients adhering to this . Post-intervention , the decrease in IL-6 and in fasting glucose was significantly higher in Currant patients who lost BW compared to their counterparts in the Control arm . Conclusively , minimal modifications in snacking choices , such as the inclusion of dried grapes in diet , are beneficial in NAFLD patients with non-significant fibrosis ", "This study sought to examine whether consumption of two low-calorie fruit/day for 3-months can effectively improve oxidative stress , anthropometry , blood pressure and glycaemic control in type 2 diabetes mellitus . Study involved 123 patients who were assigned to receive either st and ard care or with additional dietary therapy . Dietary intervention result ed in significant reduction in malondialdehyde , plasma glucose , glycated haemoglobin and improvement in antioxidants like vitamin C and reduced glutathione when compared to controls . Mean plasma levels of vitamin C increased by 64 % ( p waist circumference , waist-to-hip ratio , blood pressure , vitamin E and superoxide dismutase in the intervention group at follow-up . Diet rich in fruits can improve some antioxidants which are likely to reduce oxidative stress in type 2 diabetes . Regular consumption of fruits can lower the glycaemic status in these patients . The study supports the usefulness of plasma vitamin C as a biomarker for fruit intake", "BACKGROUND Chronic peanut consumption is associated with health benefits . To encourage consumption , peanuts are marketed with various flavorings , but questions have been raised as to whether seasonings offset the benefits of peanuts alone . OBJECTIVE This study sought to determine whether flavorings on peanuts affect health benefits over 12 wk . DESIGN In a r and omized , parallel-group trial , 151 participants received 42 g peanuts/d as 14-g servings of 3 different flavors ( n = 50 ) or a single flavor ( n = 25 - 26/group ) . Anthropometric indexes , blood pressure , and heart rate were measured biweekly . Cardiovascular disease risk factors ( serum lipids , insulin , glucose , and cortisol ) were assessed monthly . RESULTS No single added flavor differentially altered body weight , body fat , body mass index , heart rate , or blood indexes in the total sample . Participants at greater risk of cardiovascular disease had significantly greater mean ( ± SE ) reductions in diastolic blood pressure ( -5.0 ± 1.7 mm Hg compared with -0.7 ± 0.6 mm Hg ) , cholesterol ( -12.1 ± 8.5 mg/dL compared with + 5.6 ± 2.0 mg/dL ) , and triglycerides ( -31.7 ± 15.8 mg/dL compared with + 2.3 ± 3.0 mg/dL ) ( n = 27 , 24 , and 15 , respectively ; P greater weight gain ( 0.9 ± 0.3 kg ) compared with individual flavors alone ( 0.5 ± 0.2 kg ) ( P in fat and lean masses were not significant . CONCLUSIONS Regardless of flavoring , peanut consumption offered significant benefits to participants with elevated serum lipids and blood pressure . Sensory variety led to a small , but significant , increase in body weight in comparison with ingestion of a single flavor but no change in fat mass", "Abstract Objective : To compare effects of raisin snacks with conventional snacks on glycemia and cardiovascular risk factors . Material s and Methods : A 12–week , r and omized , controlled trial compared 3–times – a – day consumption of raisins with intake of processed snacks on glycemia and cardiovascular risk factors . Men and women were r and omized to snacks ( n = 15 ) or raisins ( n = 31 ) . Outcome measures were performed at baseline , 4 , 8 , and 12 weeks . Results : Fasting plasma glucose levels were not significantly affected by intake of raisins or snacks . Mean subject post pr and ial glucose levels were significantly reduced by raisin intake at 12 weeks ; changes with raisin intake were −13.1 mg/dL ( P = 0.003 vs baseline ; P = 0.03 vs snacks ) . Eating raisins significantly decreased glycated hemoglobin ( HbA1c ) level ( −0.12 % ; P = 0.004 ) , a significantly greater level decrease than seen with snack intake ( P = 0.036 ) . Snack intake did not significantly affect subject systolic or diastolic blood pressure ( BP ) . Raisin intake was associated with reductions in systolic blood pressure ( SBP ) at 4 , 8 , and 12 weeks with mean changes of −6.0 to 10.2 mmHg ; all these changes were statistically significant ( P = 0.015 to 0.001 ) . Raisins were associated with significantly greater changes in diastolic blood pressure ( DBP ) at 4 , 8 , and 12 weeks than snacks ( P ) . Body weight did not significantly change within or between groups . Conclusions : Regular consumption of raisins may reduce glycemia and cardiovascular risk factors , including BP rate", "Overtly hypertriglyceridemic patients with non-insulin-dependent diabetes mellitus were given a control diet containing 120 g of sucrose and 50 percent carbohydrate , and later r and omly assigned to receive isocaloric high- ( 220 g ) , intermediate- ( 120 g ) , or low- ( less than 3 g ) sucrose/carbohydrate diets for four weeks . The low-sucrose diet group demonstrated a modest but significant decrease in mean fasting serum glucose level in the first week only , although this change was no different from the other two dietary groups and was not sustained . All groups had little change in late postpr and ial serum glucose levels from control values , and no significant alterations in 24-hour glycosuria . The high-sucrose diet group demonstrated a significant increase in fasting serum triglyceride levels by the second week of the study , whereas the intermediate- and low-sucrose diet groups showed a decrease in mean fasting triglyceride levels . In contrast , the low-sucrose diet group 's late postpr and ial serum triglyceride levels increased by the fourth week , whereas levels fell in the high-sucrose diet group . Mean fasting serum cholesterol concentrations decreased from control values in the high-sucrose diet group . Thus , although very high sucrose and carbohydrate consumption is clearly deleterious to fasting tryglyceride levels in non-insulin-dependent diabetes mellitus with preexisting hypertriglyceridemia , it appears that low dietary sucrose and carbohydrate proportions do not further improve prepr and ial glycemia and glycosuria and may adversely affect late postpr and ial serum triglyceride concentration . This study suggests that isocaloric sucrose and carbohydrate restriction below usual daily levels ( 120 g per day ) offers no consistent benefit in glycemia or lipid control in overt type II diabetes", "OBJECTIVES Dried fruits , like their fresh homologues , contain relatively high concentrations of antioxidants . The aim of this study was to determine the health outcomes of raisin consumption on patients with diabetes . METHODS We examined the effects of dried grapes ( Vitis vinifera ) cultivated in Greece , namely Corinthian Raisins ( CR ) on blood pressure , fasting glucose , glucated hemoglobin ( HbA1c ) , lipid peroxidation , high-sensitivity C-reactive protein , antioxidant status , and cytokines in patients with type 2 diabetes mellitus ( T2DM ) . Forty-eight well-controlled patients with T2DM from the diabetes outpatient clinic of our hospital were recruited to a two-armed , r and omized , controlled , 24-wk prospect i ve intervention trial in order to examine the health outcomes of CR consumption . All participants were reported to consume less fruits and vegetables than the recommended amount of five servings daily . Participants in the intervention were instructed to consume CR equal to two fruit servings ( 36 g/d ) , replacing snacks with similar energy density twice during the day . Anthropometric and blood pressure measurements , assessment of dietary intake , and fasting blood draws were conducted at baseline and at week 24 . Also , phenolic compounds present in CR were analyzed in plasma of the patients . t Test for parametric data and Mann-Whitney test or Wilcoxon test for non-parametric data were performed . Significance was set at P Body weight , glycemic control , and lipid profile were not affected in either arm . Patients in the CR arm reduced their diastolic blood pressure and increased their total antioxidant potential significantly compared with baseline . The differences between the two groups at week 24 were significant . No change in high-sensitivity C-reactive protein was observed . A significant difference in plasma circulating p-hydroxybenzoic acid was observed between groups at the end of the trial . CONCLUSIONS Our study shows that naturally CR may improve health features in patients with well-controlled T2DM", "Several studies show that sucrose does not aggravate hyperglycemia in type II diabetes mellitus , but sucrose is still restricted in dietary recommendations . Since sucrose in high carbohydrate diets elevates fasting triglyceride levels , the effects of sucrose were evaluated in diets with fixed carbohydrate levels . Eighteen diabetic volunteers receiving no medication were given weight maintenance diets with 50 percent carbohydrate , 35 percent fat , 15 percent protein , and 120 g of sucrose for 10 days as in patients . They were then r and omly assigned diets of similar composition with either 220 g of sucrose ( high sucrose diet ) or less than 3 g of sucrose daily ( complex carbohydrate [ CHO ] diet ) for one additional month . There were no differences in fasting , one- , two- , and three-hour post-lunch serum glucose levels ; 24-hour glycosuria ; glycohemoglobin levels ; fasting and postpr and ial serum triglyceride levels , or fasting high-density lipoprotein-cholesterol levels . Twelve patients with preexisting higher triglyceridemia had similar trends , but the postpr and ial triglyceride levels were lower in the high sucrose diet group of this subset ( p less than 0.05 in the third week ) . Postpr and ial serum insulin levels declined in the second week on the complex CHO diet . More than 75-fold difference in sucrose intake with constant carbohydrate and fat did not affect glycemic or triglyceridemic control in type II diabetic patients . The reported high sucrose-carbohydrate-induced rise in fasting triglyceridemia was not present when a diet high in sucrose was given without changing total carbohydrate", "An increasing amount of fructose in the diet is suggested to play a causal role in the pathogenesis of the metabolic syndrome , type 2 diabetes and fatty liver . Our aim was to investigate and compare the effects of very high fructose and very high glucose in hyperenergetic diets on glucose and lipid metabolism and on fat depots in healthy humans . We conducted an exploratory , prospect i ve , r and omised , single-blinded , intervention trial . Participants in addition to a balanced weight-maintaining diet received 150 g of fructose or glucose/d for 4 weeks . Insulin sensitivity was estimated from oral glucose tolerance tests . Visceral and subcutaneous abdominal fat was determined with MRI . Liver fat and intramyocellular lipids of the tibialis anterior muscle were measured with (1)H magnetic resonance spectroscopy . A total of twenty healthy subjects ( fructose group n 10 and glucose group n 10 ; twelve males and eight females ) completed the study . They had a mean age of 30·5 ( SEM 2·0 ) years and a mean BMI of 25·9 ( SEM 0·5 ) kg/m(2 ) . Insulin sensitivity appeared to decrease both in the fructose and glucose groups . TAG markedly increased in the fructose group . No strong alterations or treatment effects were found for liver fat , visceral fat , subcutaneous abdominal fat and intramyocellular lipids of the tibialis anterior muscle . In conclusion , the effects of very high fructose and very high glucose in hyperenergetic diets on glucose metabolism and body fat composition were not different in the healthy participants of the present study . However , elevation of plasma TAG seemed to be fructose-specific", "CONTEXT Increased hepatic de novo lipogenesis ( DNL ) in response to dietary sugar is implicated in the pathophysiology of fatty liver . Saturated fatty acids are the product of DNL and exert lipotoxic effects that promote liver fat accumulation . Desaturation of fatty acids by stearoyl-CoA desaturase 1 ( SCD1 ) can prevent these deleterious effects . Here we investigated whether DNL and SCD1 are activated in parallel by dietary sugar and influence liver fat accumulation . METHODS In 20 healthy subjects ( eight females and 12 males , aged 30.5 ± 2.0 yr , body mass index 25.9 ± 0.5 kg/m(2 ) ) who received a 4-wk lipogenic diet supplemented with 150 g/d of monosaccharides , hepatic SCD1 activity and DNL were determined using vali date d fatty acid ratios ( 16:1n-7/16:0 ; 16:0/18:2n-6 ) in very low-density lipoprotein triglycerides . Liver fat content was measured by localized (1)H-magnetic resonance spectroscopy . RESULTS At baseline , liver fat content was positively associated with the DNL ( r = 0.54 , P = 0.01 ) but not the SCD1 activity index ( r = 0.16 , P = 0.49 ) . Dietary sugar supplementation increased liver fat content and DNL and SCD1 activity indices ( + 33 , + 19 , and + 8 % , respectively ) . The increase of the DNL index was strongly related to the changes in liver fat content during the sugar supplementation ( r = 0.75 , P = 0.0001 ) but showed no association with changes in the SCD1 activity ( P > 0.35 ) . After the monosaccharide supplementation , the DNL index was still positively associated with liver fat content ( r = 0.52 , P = 0.02 ) , whereas SCD1 activity showed a strong negative correlation with liver fat content ( r = -0.63 , P = 0.002 ) . CONCLUSIONS DNL is closely linked with hepatic steatosis under dietary conditions rich in monosaccharides . Our data suggest that the individual hepatic SCD1 activity is a determinant of liver fat accumulation under lipogenic dietary conditions", "Abstract Objective : To study the effects of snacking based on fast acting carbohydrates ( c and y ) or fat and protein ( peanuts ) in a prospect i ve r and omized , parallel intervention study . Methods : Basal metabolic rate ( BMR ) and cardiovascular risk factors were measured before and after hyper-alimentation by addition of 20kcal/kg ( 84kJ/kg ) body weight of either c and y or roasted peanuts , to the regular caloric intake , for two weeks in healthy subjects . Eleven men and 14 women completed the r and omized study . Results : Energy-intake increased similarly in the groups ( c and y : + 46.1±35 % , peanuts : + 46.8±28 % p=0.96 ) . Body-weight ( c and y : from 67.3±7.6 kg to 68.1±7.3 kg , p=0.01 , nuts : from 68.7±6.1 kg to 69.0±5.7 kg p=0.3 ) and waist circumference increased significantly only in the c and y group . At the end of the study LDL cholesterol ( c and y : 2.6±0.4mmol/l peanuts : 2.1±0.4mmol/l , p=0.005 ) and ApoB/ApoA-1-ratio ( c and y : 0.68±0.16 peanuts 0.53±0.11 , p=0.01 ) were higher in the c and y group than in the peanut group . On the other h and , BMR increased only in the peanut group ( c and y : from 6.657±1.1MJ/24h to 6.762±1.1MJ/24h , p=0.3 nuts : from 6.896±0.98MJ/24h to 7.256±1.1MJ/24h , p=0.02 ) . Conclusion : Two weeks of snacking based on peanuts does not cause the same negative metabolic effects as an isocaloric diet in which the snacking is based on short acting carbohydrates in the form of c and y in non-obese healthy subjects", "BACKGROUND Both nutritional and genetic factors are involved in the pathogenesis of nonalcoholic fatty liver disease and insulin resistance . OBJECTIVE The aim was to assess the effects of fructose , a potent stimulator of hepatic de novo lipogenesis , on intrahepatocellular lipids ( IHCLs ) and insulin sensitivity in healthy offspring of patients with type 2 diabetes (OffT2D)--a subgroup of individuals prone to metabolic disorders . DESIGN Sixteen male OffT2D and 8 control subjects were studied in a crossover design after either a 7-d isocaloric diet or a hypercaloric high-fructose diet ( 3.5 g x kg FFM(-1 ) x d(-1 ) , + 35 % energy intake ) . Hepatic and whole-body insulin sensitivity were assessed with a 2-step hyperinsulinemic euglycemic clamp ( 0.3 and 1.0 mU x kg(-1 ) x min(-1 ) ) , together with 6,6-[2H2]glucose . IHCLs and intramyocellular lipids ( IMCLs ) were measured by 1H-magnetic resonance spectroscopy . RESULTS The OffT2D group had significantly ( P IHCLs ( + 94 % ) , total triacylglycerols ( + 35 % ) , and lower whole-body insulin sensitivity ( -27 % ) than did the control group . The high-fructose diet significantly increased IHCLs ( control : + 76 % ; OffT2D : + 79 % ) , IMCLs ( control : + 47 % ; OffT2D : + 24 % ) , VLDL-triacylglycerols ( control : + 51 % ; OffT2D : + 110 % ) , and fasting hepatic glucose output ( control : + 4 % ; OffT2D : + 5 % ) . Furthermore , the effects of fructose on VLDL-triacylglycerols were higher in the OffT2D group ( group x diet interaction : P 7-d high-fructose diet increased ectopic lipid deposition in liver and muscle and fasting VLDL-triacylglycerols and decreased hepatic insulin sensitivity . Fructose-induced alterations in VLDL-triacylglycerols appeared to be of greater magnitude in the OffT2D group , which suggests that these individuals may be more prone to developing dyslipidemia when challenged by high fructose intakes . This trial was registered at clinical trials.gov as NCT00523562", "BACKGROUND Resistant starch ( RS ) and whey protein are thought to be effective nutrients for reducing glycemic responses . OBJECTIVE We aim ed to determine the effect of varying the sucrose , RS , and whey protein content of cereal bars on glucose and insulin responses . DESIGN Twelve healthy subjects [ mean ± SD age : 36 ± 12 y ; mean ± SD body mass index ( in kg/m2 ) : 24.9 ± 2.7 ] consumed 40 g available-carbohydrate ( avCHO ) portions of 5 whole-grain cereal bars that contained varying amounts of RS and whey protein concentrate [ WPC ; 70 % protein ; RS : WPC , % wt : wt : 15:0 ( Bar15/0 ) ; 15:0 , low in sucrose ( Bar15/0LS ) ; 15:5 ( Bar15/5 ) ; 10:5 ( Bar10/5 ) ; and 10:10 ( Bar10/10 ) ] and 2 portion sizes of a control bar low in whole grains , protein , and RS [ control 1 contained 40 g avCHO ( Control1 ) ; control 2 contained total carbohydrate equal to Bar15/0LS ( Control2 ) ] on separate days by using a r and omized crossover design . Glucose and insulin responses in vivo and carbohydrate digestibility in vitro were measured over 3 h. RESULTS Incremental area under the curve ( iAUC ) over 0 - 3 h for glucose ( min × mmol/L ) differed significantly between treatments ( P P did not differ significantly . Higher protein content was associated with a lower glucose iAUC ( P = 0.028 ) and a higher insulin-to-glucose iAUC ratio ( P = 0.002 ) All 5 RS-containing bars were digested in vitro ∼30 % more slowly than the control bars ( P vitro . Glucose and insulin responses elicited by high-RS , whey protein-free bars were similar to those elicited from control bars . CONCLUSIONS The inclusion of RS in cereal bar formulations did not reduce glycemic responses despite slower starch digestion in vitro . Thus , caution is required when extrapolating in vitro starch digestibility to in vivo glycemic response . The inclusion of whey protein in cereal bar formulations to reduce glycemic response requires caution because this may be associated with a disproportionate increase in insulin as judged by an increased insulin-to-glucose iAUC ratio . This trial was registered at clinical trials.gov as NCT02537587", "AIM A pro-thrombotic , pro-inflammatory diet can play a causative role in atherosclerotic-cardiovascular diseases . Dietary intervention studies provide insight into their pathophysiological manifestations and opportunities for prevention and management . We previously showed in an acute-meal setting that a beverage containing polyphenolic- and antioxidant-rich strawberry ( Fragaria ) vs placebo attenuated postpr and ial ( fed-state ) increases in biomarkers of oxidative and inflammatory stress , and insulin concentrations , induced by a high carbohydrate/fat ( HCF ) meal . In the present study , we aim ed to extend our findings and investigate hypotheses related to the effects of chronic/6-week ( wk ) strawberry consumption on HCF meal-induced increases in glucose , insulin , and indicators of inflammation and hemostasis . METHODS In a crossover design , 14 women and 10 men ( mean age , BMI : 50.9±15 years , 29.2±2.3 kg/m(2 ) , respectively ) , were r and omized to a 6-wk strawberry or placebo beverage followed by an HCF meal with assessment s for 6-hours ( h ) postpr and ially . RESULTS HCF meal responses after 6-wk strawberry beverage showed significantly attenuated postpr and ial PAI-1 concentrations compared to the placebo ( p = 0.002 ) ; the difference was most notable at 6 h. The IL-1 β response was attenuated with strawberry compared to the placebo ( p = 0.05 ) . IL-6 attenuation was apparent but non-significant ; IL-6 rose significantly from baseline to 6 h after the HCF meal following a placebo ( p ≤0.01 ) , although it remained relatively flat following the strawberry beverage from fasting to 6 h. No significant treatment-related differences were apparent for platelet aggregation , hsCRP , TNF-α , insulin , or glucose . CONCLUSION These data are the first to suggest that regular consumption of strawberry , a polyphenolic- and antioxidant-rich fruit , may provide protection from HCF meal-induced increases in fibrinolytic and inflammatory factors in at-risk men and women", "BACKGROUND Studies of cocoa suggest an array of cardiovascular benefits ; however , the effects of daily intake of sugar-free and sugar-sweetened cocoa beverages on endothelial function ( EF ) have yet to be established . METHODS 44 adults ( BMI 25 - 35 kg/m2 ) participated in a r and omized , controlled , crossover trial . Participants were r and omly assigned to a treatment sequence : sugar-free cocoa beverage , sugar-sweetened cocoa beverage , and sugar-sweetened cocoa-free placebo . Treatments were administered daily for 6 weeks , with a 4-week washout period . RESULTS Cocoa ingestion improved EF measured as flow-mediated dilation ( FMD ) compared to placebo ( sugar-free cocoa : change , 2.4 % [ 95 % CI , 1.5 to 3.2 ] vs. -0.8 % [ 95 % CI , -1.9 to 0.3 ] ; difference , 3.2 % [ 95 % CI , 1.8 to 4.6 ] ; p : change , 1.5 % [ 95 % CI , 0.6 to 2.4 ] vs. -0.8 % [ 95 % CI , -1.9 to 0.3 ] ; difference , 2.3 % [ 95 % CI , 0.9 to 3.7 ] ; p=0.002 ) . The magnitude of improvement in FMD after consumption of sugar-free versus sugar-sweetened cocoa was greater , but not significantly . Other biomarkers of cardiac risk did not change appreciably from baseline . BMI remained stable throughout the study . CONCLUSIONS Daily cocoa ingestion improves EF independently of other biomarkers of cardiac risk , and does not cause weight gain . Sugar-free preparations may further augment endothelial function" ]	4118a036-06ff-11f0-808a-c43d1ab1c353
UNLABELLED SUBJECT OF THE EVIDENCE -BASED ANALYSIS : The purpose of this evidence based analysis report is to examine the safety and effectiveness of point-of-care ( POC ) international normalized ratio ( INR ) monitoring devices for patients on long-term oral anticoagulation therapy ( OAT ) . CLINICAL NEED TARGET POPULATION AND CONDITION Long-term OAT is typically required by patients with mechanical heart valves , chronic atrial fibrillation , venous thromboembolism , myocardial infa rct ion , stroke , and /or peripheral arterial occlusion . It is estimated that approximately 1 % of the population receives anticoagulation treatment and , by applying this value to Ontario , there are an estimated 132,000 patients on OAT in the province , a figure that is expected to increase with the aging population . Patients on OAT are regularly monitored and their medications adjusted to ensure that their INR scores remain in the therapeutic range . This can be challenging due to the narrow therapeutic window of warfarin and variation in individual responses . Optimal INR scores depend on the underlying indication for treatment and patient level characteristics , but for most patients the therapeutic range is an INR score of between 2.0 and 3.0 . The current st and ard of care in Ontario for patients on long-term OAT is laboratory-based INR determination with management carried out by primary care physicians or anticoagulation clinics ( ACCs ) . Patients also regularly visit a hospital or community-based facility to provide a venous blood sample s ( venipuncture ) that are then sent to a laboratory for INR analysis . Experts , however , have commented that there may be under-utilization of OAT due to patient factors , physician factors , or regional practice variations and that sub-optimal patient management may also occur . There is currently no population -based Ontario data to permit the assessment of patient care , but recent systematic review s have estimated that less that 50 % of patients receive OAT on a routine basis and that patients are in the therapeutic range only 64 % of the time . OVERVIEW OF POC INR DEVICES POC INR devices offer an alternative to laboratory-based testing and venipuncture , enabling INR determination from a fingerstick sample of whole blood . Independent evaluations have shown POC devices to have an acceptable level of precision . They permit INR results to be determined immediately , allowing for more rapid medication adjustments . POC devices can be used in a variety of setting s including physician offices , ACCs , long-term care facilities , pharmacies , or by the patients themselves through self-testing ( PST ) or self-management ( PSM ) techniques . With PST , patients measure their INR values and then contact their physician for instructions on dose adjustment , whereas with PSM , patients adjust the medication themselves based on pre-set algorithms . These models are not suitable for all patients and require the identification and education of suitable c and i date s. Potential advantages of POC devices include improved convenience to patients , better treatment compliance and satisfaction , more frequent monitoring and fewer thromboembolic and hemorrhagic complications . Potential disadvantages of the device include the tendency to underestimate high INR values and overestimate low INR values , low thromboplastin sensitivity , inability to calculate a mean normal PT , and errors in INR determination in patients with antiphospholipid antibodies with certain instruments . Although treatment satisfaction and quality of life ( QoL ) may improve with POC INR monitoring , some patients may experience increased anxiety or preoccupation with their disease with these strategies . EVIDENCE -BASED ANALYSIS METHODS RESEARCH QUESTIONS 1 . EffectivenessDoes POC INR monitoring improve clinical outcomes in various setting s compared to st and ard laboratory-based testing?Does POC INR monitoring impact patient satisfaction , QoL , compliance , acceptability , convenience compared to st and ard laboratory-based INR determination ? Setting s include primary care setting s with use of POC INR devices by general practitioners or nurses , ACCs , pharmacies , long-term care homes , and use by the patient either for PST or PSM . 2 . Cost-effectivenessWhat is the cost-effectiveness of POC INR monitoring devices in various setting s compared to st and ard laboratory-based INR determination ? INCLUSION CRITERIA English- language RCTs , systematic review s , and meta-analysesPUBLICATION DATE S : 1996 to November 25 , 2008 POPULATION : patients on OATINTERVENTION : anticoagulation monitoring by POC INR device in any setting including anticoagulation clinic , primary care ( general practitioner or nurse ) , pharmacy , long-term care facility , PST , PSM or any other POC INR strategy MINIMUM SAMPLE SIZE : 50 patients Minimum follow-up period : 3 monthsCOMPARATOR : usual care defined as venipuncture blood draw for an INR laboratory test and management provided by an ACC or individual practitioner OUTCOMES Hemorrhagic events , thromboembolic events , all-cause mortality , anticoagulation control as assessed by proportion of time or values in the therapeutic range , patient reported outcomes including satisfaction , QoL , compliance , acceptability , convenience EXCLUSION CRITERIA Non- RCTs , before-after studies , quasi-experimental studies , observational studies , case reports , case series , editorials , letters , non- systematic review s , conference proceedings , abstract s , non-English articles , duplicate publications Studies where POC INR devices were compared to laboratory testing to assess test accuracy Studies where the POC INR results were not used to guide patient management METHOD OF REVIEW A search of electronic data bases ( OVID MEDLINE , MEDLINE In-Process & Other Non-Indexed Citations , EMBASE , The Cochrane Library , and the International Agency for Health Technology Assessment [ INAHTA ] data base ) was undertaken to identify evidence published from January 1 , 1998 to November 25 , 2008 . Studies meeting the inclusion criteria were selected from the search results . Reference lists of selected articles were also checked for relevant studies . SUMMARY OF FINDINGS Five existing review s and 22 articles describing 17 unique RCTs met the inclusion criteria . Three RCTs examined POC INR monitoring devices with PST strategies , 11 RCTs examined PSM strategies , one RCT included both PST and PSM strategies and two RCTs examined the use of POC INR monitoring devices by health care professionals . ANTICOAGULATION CONTROL Anticoagulation control is measured by the percentage of time INR is within the therapeutic range or by the percentage of INR values in the therapeutic range . Due to the differing method ologies and reporting structures used , it was deemed inappropriate to combine the data and estimate whether the difference between groups would be significant . Instead , the results of individual studies were weighted by the number of person-years of observation and then pooled to calculate a summary measure . Across most studies , patients in the intervention groups tended to have a higher percentage of time and values in the therapeutic target range in comparison to control patients . When the percentage of time in the therapeutic range was pooled across studies and weighted by the number of person-years of observation , the difference between the intervention and control groups was 4.2 % for PSM , 7.2 % for PST and 6.1 % for POC use by health care practitioners . Overall , intervention patients were in the target range 69 % of the time and control patients were in the therapeutic target range 64 % of the time leading to an overall difference between groups of roughly 5 % . MAJOR COMPLICATIONS AND DEATHS There was no statistically significant difference in the number of major hemorrhagic events between patients managed with POC INR monitoring devices and patients managed with st and ard laboratory testing ( OR = 0.74 ; 95 % CI : 0.52- 1.04 ) . This difference was non-significant for all POC strategies ( PSM , PST , health care practitioner ) . Patients managed with POC INR monitoring devices had significantly fewer thromboembolic events than usual care patients ( OR = 0.52 ; 95 % CI : 0.37 - 0.74 ) . When divided by POC strategy , PSM result ed in significantly fewer thromboembolic events than usual care ( OR = 0.46 . ; 95 % CI : 0.29 - 0.72 ) . The observed difference in thromboembolic events for PSM remained significant when the analysis was limited to major thromboembolic events ( OR = 0.40 ; 95 % CI : 0.17 - 0.93 ) , but was non-significant when the analysis was limited to minor thromboembolic events ( OR = 0.73 ; 95 % CI : 0.08 - 7.01 ) . PST and GP/Nurse strategies did not result in significant differences in thromboembolic events , however there were only a limited number of studies examining these interventions . No statistically significant difference was observed in the number of deaths between POC intervention and usual care control groups ( OR = 0.67 ; 95 % CI : 0.41 - 1.10 ) . This difference was non-significant for all POC strategies . Only one study reported on survival with 10-year survival rate of 76.1 % in the usual care control group compared to 84.5 % in the PSM group ( P=0.05 ) . ES Table 1 : Summary Results of Meta-Analyses of Major Complications and Deaths in POC INR Monitoring Studies EventNo . of trials ( patients ) OR(M-H , R and om Effects)95 % CIMajor Haemorrhages16 (5057)0.740.52 to 1.04Thromboembolic events16 (5057)0.520.37 to 0.74Deaths11 (2906)0.670.41 to 1.10 PATIENT SATISFACTION AND QUALITY OF LIFE : Quality of life measures were reported in eight studies comparing POC INR monitoring to st and ard laboratory testing using a variety of measurement tools . It was thus not possible to calculate a quantitative summary measure . The majority of studies reported favourable impacts of POC INR monitoring on QoL and found better treatment satisfaction with POC monitoring . Results from a pre- analysis patient and caregiver focus group conducted in Ontario also indicated improved patient QoL with POC monitoring . (	[ "Background Comparison of self-management of oral anticoagulant therapy versus conventional management has been hindered by use of different methods . We tested the hypothesis that there is no difference in the International Normalized Ratio ( INR ) variability , INR level , and coumarin dose among patients r and omized to conventional management versus self-management . Methods The study design included uniform analysis of blinded control blood sample s in both treatment arms . Ninety-two patients were r and omly assigned to either self-management of oral anticoagulant therapy ( including a teaching program for self-management followed by 6 months of independent self-management ) or 6 months of conventional management . The endpoints were the variance ( median square of the st and ard deviation ) of the INR value , the median INR-value ( using a blinded control sample analyzed monthly by a reference laboratory ) , and the coumarin dose . Results Self-management was associated with a statistically significant smaller variance in INR values , a higher median INR value , and a higher dose of warfarin compared with conventional management . No difference was found in the group of patients using phenprocoumon . Conclusion Training and implementation of patient self-management leads to a smaller variance in INR values , a higher median INR value and a higher dose of coumarin compared with results obtained for conventionally managed patients", "BACKGROUND There is increased pressure on primary care physicians to monitor oral anticoagulation . OBJECTIVE To test the None hypothesis that oral anticoagulation care can be provided at least as well in primary care through a nurse-led clinic , involving near-patient testing and computerized decision support software , compared with routine hospital management based on a variety of clinical outcome measures . METHODS A r and omized , controlled trial in 12 primary care practice s in Birmingham , Engl and ( 9 intervention and 3 control ) . Two control population s were used : patients individually r and omly allocated as controls in the intervention practice s ( intra practice controls ) and all patients in control practice s ( inter practice controls ) . Intervention practice s ' patients were r and omized to the intervention ( practice -based anticoagulation clinic ) or control ( hospital clinic ) group . The main outcome measure was therapeutic control of the international normalized ratio . RESULTS Three hundred sixty-seven patients were recruited ( 122 intervention patients , 102 intra practice control patients , and 143 inter practice control patients ) . St and ard measures of control of the international normalized ratio ( point prevalence ) showed no significant difference between the intervention and control groups . Data on proportion of time spent in the international normalized ratio range showed significant improvement for patients in the intervention group ( paired t test , P = .008 ) . CONCLUSIONS Nurse-led anticoagulation clinics can be implemented in novice primary care setting s by means of computerized decision support software and near-patient testing . Care given by this model is at least as good as routine hospital follow-up . The model is generalizable to primary health care centers operating in developed health care systems", "Self-management is safe and reliable in patients with long-term oral anticoagulation ( OAC ) . However , no study has yet assessed the safety and efficacy of OAC self-management in elderly patients with major thromboembolic and haemorrhagic complications as primary outcomes . In this multi-centre , open , r and omised controlled trial , patients aged 60 years or more were r and omised into the self-management group ( SMG ) ( N = 99 ) or routine care group ( RCG ) ( N = 96 ) . We describe the rationale , design , baseline characteristics and interim analyses of oral anticoagulation control quality within the first year of follow-up . The medians of the squared international normalised ratio ( INR ) value deviations after six and 12 months were significantly lower in the SMG with medians of 0.16 and 0.16 compared to the RCG with medians of 0.25 and 0.25 . The percentage of time within target range and the percentage of INR measurements within target range were significantly higher in the SMG versus the RCG within the first six months ( medians 71 % vs. 58 % and 69 % vs. 57 % ) , and during the second six months of the study ( 75 % vs. 67 % and 72 % vs. 57 % ) . The numbers of all thromboembolic events requiring hospitalisation , major bleeding events , and deaths were similar in both groups . These preliminary results suggest that self-management of oral anticoagulation is safe and feasible for elderly patients willing to participate in a structured training programme", "CONTEXT Control of oral anticoagulation therapy has been reported to often be inadequate . Previous retrospective investigations suggest that patients ' self-adjustment of oral anticoagulants may lead to improved control . OBJECTIVE To investigate the effects of patients ' self-management of oral anticoagulation therapy on accuracy of control and measures of treatment-related quality of life . DESIGN R and omized , single-blind , multicenter trial . SETTING AND PARTICIPANTS A total of 179 patients receiving long-term oral anticoagulation treatment were enrolled at 5 referral centers in Germany . INTERVENTION Patients were r and omized to an oral anticoagulation self-management group based on a structured treatment and teaching program and international normalized ratio ( INR ) self-monitoring . The control group received conventional care as provided by family physicians , including referral to specialists if necessary . MAIN OUTCOME MEASURES Deviation of INR values from the individual INR target range ( squared ) and the 5 categories of treatment-related quality of life . RESULTS Deviation of INR value from the mean of the INR target range was significantly lower in the intervention group at 3-month ( squared INR deviation , 0.59 vs 0.95 ; P INR values within the target range more often ( repeated measurement analysis for categorical data , P=.006 ) . The results were mainly due to less frequent suboptimal INR values in the intervention group ( 32.8 % vs 50.0 % [ P=.03 ] at 3-month , and 33.7 % vs 48.2 % [ P=.08 ] at 6-month follow-up ) . Treatment-related quality -of-life measures , especially treatment satisfaction scores , were significantly higher in the intervention group compared with controls . CONCLUSIONS An anticoagulation education program that includes self-management of anticoagulation therapy results in improved accuracy of anticoagulation control and in treatment-related quality -of-life measures . Further studies are needed to describe whether the program will reduce risk of bleeding or thromboembolism", "AIMS In Belgium , general practitioners ( GPs ) mainly manage oral anticoagulation therapy . To improve the quality of oral anticoagulation management by GPs and to compare different models and interventions , a r and omized clinical trial was performed . METHODS AND RESULTS Stratified r and omization divided 66 GP- practice s into four groups . A 6-month retrospective analysis assessed the baseline quality . In the prospect i ve study , each group received education on oral anticoagulation , anticoagulation files , and patient information booklets ( groups A , B , C , and D ) . Group B additionally received feedback every 2 months on their anticoagulation performance ; group C determined the international normalized ratio ( INR ) with a CoaguChek device in the doctor 's office or at the patient 's home ; and group D received Dawn AC computer assisted advice for adapting oral anticoagulation . For the different groups , the time spent in target INR range ( Rosendaal 's method ) and adverse events related to anticoagulation were determined and compared with the same quality indicators at baseline . There was a significant increase in per cent of time within 0.5 INR from target , from 49.5 % at baseline to 60 % after implementing the different interventions . However , neither the per cent in target range nor the event rates differed among the four groups . CONCLUSION The interventions significantly improved the quality of management of oral anticoagulation by Belgian GPs , mainly as a result of an education and support programme", "Background Point of care testing ( PoCT ) may be a useful adjunct in the management of chronic conditions in general practice ( GP ) . The provision of pathology test results at the time of the consultation could lead to enhanced clinical management , better health outcomes , greater convenience and satisfaction for patients and general practitioners ( GPs ) , and savings in costs and time . It could also result in inappropriate testing , increased consultations and poor health outcomes result ing from inaccurate results . Currently there are very few r and omised controlled trials ( RCTs ) in GP that have investigated these aspects of PoCT . Design / Methods The Point of Care Testing in General Practice Trial ( PoCT Trial ) was an Australian Government funded multi-centre , cluster r and omised controlled trial to determine the safety , clinical effectiveness , cost effectiveness and satisfaction of PoCT in a GP setting .The PoCT Trial covered an 18 month period with the intervention consisting of the use of PoCT for seven tests used in the management of patients with diabetes , hyperlipidaemia and patients on anticoagulant therapy . The primary outcome measure was the proportion of patients within target range , a measure of therapeutic control . In addition , the PoCT Trial investigated the safety of PoCT , impact of PoCT on patient compliance to medication , stakeholder satisfaction , cost effectiveness of PoCT versus laboratory testing , and influence of geographic location . Discussion The paper provides an overview of the Trial Design , the rationale for the research methodology chosen and how the Trial was implemented in a GP environment . The evaluation protocol and data collection processes took into account the large number of patients , the broad range of practice types distributed over a large geographic area , and the inclusion of pathology test results from multiple pathology laboratories . The evaluation protocol developed reflects the complexity of the Trial setting , the Trial Design and the approach taken within the funding provided . The PoCT Trial is regarded as a pragmatic RCT , evaluating the effectiveness of implementing PoCT in GP and every effort was made to ensure that , in these circumstances , internal and external validity was maintained . Trial Registration", "Background : Self management of anticoagulation : a r and omised trial ( SMART ) was the first large scale UK trial to assess clinical and cost effectiveness of patient self management ( PSM ) of oral anticoagulation therapy compared to routine care . SMART showed that while PSM was as clinical ly effective as routine care , it was not as cost effective . SMART adds to the growing body of trial data to support PSM ; however there are no data on clinical effectiveness and cost of PSM in routine care . Aim : To evaluate clinical effectiveness of PSM compared to routine care outside trial conditions . Methods : A retrospective multicentre matched control study . 63 PSM patients from primary care in the West Midl and s were matched by age and international normalised ratio ( INR ) target with controls . INR results were collected for the period 1 July 2003–30 June 2004 . The primary outcome measure was INR control . Results : 38 PSM and 40 control patients were recruited . INR percentage time in range was 70 % PSM vs 64 % controls . 60 % PSM were having a regular clinical review , 45 % were performing an internal quality control ( IQC ) test and 82 % were performing external quality assurance ( EQA ) on a regular basis . Conclusion : PSM outside trial conditions is as clinical ly effective as routine UK care", "Background : The increase in numbers of patients receiving warfarin treatment has led to the development of alternative models of service delivery for oral anticoagulant monitoring . Patient self management for oral anticoagulation is a model new to the UK . This r and omised trial was the first to compare routine primary care management of oral anticoagulation with patient self management . Aim : To test whether patient self management is as safe , in terms of clinical effectiveness , as primary care management within the UK , as assessed by therapeutic international normalised ratio ( INR ) control . Method : Patients receiving warfarin from six general practice s who satisfied study entry criteria were eligible to enter the study . Eligible patients were r and omised to either intervention ( patient self management ) or control ( routine primary care management ) for six months . The intervention comprised two training sessions of one to two hours duration . Patients were allowed to undertake patient self management on successful completion of training . INR testing was undertaken using a Coaguchek device and regular internal/external quality control tests were performed . Patients were advised to perform INR tests every two weeks , or weekly if a dose adjustment was made . Dosage adjustment was undertaken using a simple dosing algorithm . Results : Seventy eight of 206 ( 38 % ) patients were eligible for inclusion and , of these , 35 ( 45 % ) declined involvement or withdrew from the study . Altogether , 23 intervention and 26 control patients entered the study . There were no significant differences in INR control ( per cent time in range : intervention , 74 % ; control , 77 % ) . There were no serious adverse events in the intervention group , with one fatal retroperitoneal haemorrhage in the control group . Costs of patient self management were significantly greater than for routine care ( £ 90 v £ 425/patient/year ) . Conclusion : These are the first UK data to demonstrate that patient self management is as safe as primary care management for a selected population . Further studies are needed to eluci date whether this model of care is suitable for a larger population", "Background and Purpose — Warfarin is the most effective stroke prevention medication for high-risk individuals with atrial fibrillation , yet it is often underused . This study examined the magnitude of this problem in a large contemporary , prospect i ve stroke registry . Methods — We analyzed data from the Registry of the Canadian Stroke Network , a prospect i ve data base of consecutive patients with stroke admitted to 12 design ated stroke centers in Ontario ( 2003 to 2007 ) . We included patients admitted with an acute ischemic stroke who ( 1 ) had a known history of atrial fibrillation ; ( 2 ) were classified as high risk for systemic emboli according to published guidelines ; and ( 3 ) had no known contraindications to anticoagulation . Primary end points were the use of prestroke antithrombotic medications and admission international normalized ratio . Results — Among patients admitted with a first ischemic stroke who had known atrial fibrillation ( n=597 ) , strokes were disabling in 60 % and fatal in 20 % . Preadmission medications were warfarin ( 40 % ) , antiplatelet therapy ( 30 % ) , and no antithrombotics ( 29 % ) . Of those taking warfarin , three fourths had a subtherapeutic international normalized ratio ( patients with acute stroke with known atrial fibrillation were therapeutically anticoagulated ( international normalized ratio ≥2.0 ) at admission . In stroke patients with a history of atrial fibrillation and a previous transient ischemic attack or ischemic stroke ( n=323 ) , only 18 % were taking warfarin with therapeutic international normalized ratio at the time of admission for stroke , 39 % were taking warfarin with subtherapeutic international normalized ratio , and 15 % were on no antithrombotic therapy . Conclusions — In high-risk patients with atrial fibrillation admitted with a stroke , and who were c and i date s for anticoagulation , most were either not taking warfarin or were subtherapeutic at the time of ischemic stroke . Many were on no antithrombotic therapy . These findings should encourage greater efforts to prescribe and monitor appropriate antithrombotic therapy to prevent stroke in individuals with atrial fibrillation", "BACKGROUND Oral anticoagulant therapy ( OAT ) implies frequent blood checks and dose changes to prevent thromboembolic or hemorrhagic complications . This may interfere with patients ' social and working circumstances in addition to the possible stress caused by the condition necessitating this treatment . We studied whether patient self-management could be a way to improve quality of life in these patients . METHODS Within a multicenter r and omized study performed by two Dutch anticoagulation clinics , design ed to study the effect on treatment quality ( time within target range ) of different modalities of patient self-management , we looked at the effect of increased patient education ( n = 28 ) , self-monitoring of the International Normalized Ratio ( INR ) ( n = 47 ) and full patient self-management ( INR monitoring and dosing of the OAT ) ( n = 41 ) on the quality of life of the patients . This was done with the aid of a written question naire ( 32 questions , minimum score = 1 , maximum score = 6 ) at baseline ( n = 163 ) , and after 26 weeks ( n = 118 ) . We compared the results after 26 weeks with those at baseline , as well as between groups . RESULTS General treatment satisfaction was already high under routine care ( 5.11 on a scale of 1 - 6 ) and increased further through self-monitoring of the INR ( + 0.19 ) and full self-management ( + 0.32 ) . Distress ( -0.44 ) , perceived daily hassles ( -0.31 ) and strain on the social network ( -0.21 ) were reduced through full self-management . Improved patient education was associated with increased distress ( + 0.33 ) and perceived daily hassles ( + 0.23 ) . Comparison at 26 weeks between groups showed similar improvements on these outcomes for self-monitoring and self-management vs. routine care after education", "BACKGROUND Vitamin K antagonist treatment is effective for prevention and treatment of thromboembolic events but frequent laboratory control and dose-adjustment are essential . Small portable devices have enabled patient self-monitoring of anticoagulation and self-adjustment of the dose . We compared this self-management of oral anticoagulant therapy with conventional management by a specialist anticoagulation clinic in a r and omised cross-over study . METHODS 50 patients on long-term oral anticoagulant treatment were included in a r and omised controlled crossover study . Patients were self-managed or were managed by the anticoagulation clinic for a period of 3 months . After this period the alternative strategy was followed for each patient . Prothrombin time ( expressed as international normalised ratio [ INR ] ) were measured at intervals of 1 - 2 weeks in both periods without knowledge of type of management . The primary endpoint was the number of measurements within the therapeutic range ( therapeutic target value + /-50.5 INR units ) . FINDINGS There was no significant difference in the overall quality of control of anticoagulation between the two study periods . Patients were for 55 % and for 49 % of the treatment period within a range of + /-0.5 from the therapeutic target INR during self-management and anticoagulation clinic management , respectively ( p=0.06 ) . The proportion of patients who spent most time in the therapeutic target range was larger during self-management than during anticoagulation clinic-guided management . The odds ratio for a better control of anticoagulation ( defined as the period of time in the therapeutic target range ) during self-management compared with anticoagulation clinic-guided management was 4.6 ( 95 % CI 2.1 - 10.2 ) . A patient-satisfaction assessment showed superiority of self-management over conventional care . INTERPRETATION Self-management of INR in the population in this study is feasible and appears to result in control of anticoagulation that is at least equivalent to management by a specialist anticoagulation clinic . It is also better appreciated by patients . Larger studies are required to assess the effect of this novel management strategy on the incidence of thromboembolic or bleeding complications", "BACKGROUND Self-management ( SM ) of warfarin by patients is an attractive strategy , particularly if it improves anticoagulation control and can be done safely under minimal physician supervision . OBJECTIVE To compare the effect of SM with physician-management ( PM ) on the maintenance of therapeutic anticoagulation . METHODS A r and omized , open-label eight-month trial was performed . Patients 18 years of age and older were eligible if they were receiving warfarin for at least one month before enrolment and required anticoagulation for at least one year to a target international normalized ratio ( INR ) of 2.0 to 3.0 or 2.5 to 3.5 . Exclusion criteria were a known hypercoaguable disorder , mental incompetence , a language barrier or an inability to attend training sessions . Patients r and omly assigned to SM tested their INR using a point-of-care device ( Pro Time Microcogulation System , International Technidyne Corporation , USA ) and adjusted their warfarin doses using a nomogram . Patients r and omly assigned to PM received usual care from their general practitioner . The primary outcome was to demonstrate 20 % improvement in anticoagulation control by SM . RESULTS One hundred forty patients were r and omly assigned ( 70 per group ) . Thirteen patients dropped out of SM early due to an inability to self-manage . Based on intention-to-treat analysis , there was no difference in the proportion of INR in range ( SM 64.8 % versus PM 58.7 % , P=0.23 ) or time in target range ( SM 71.8 % versus PM 63.2 % , P=0.14 ) . Patients managing their own therapy spent less time below the therapeutic range ( 15.0 % versus 27.3 % , P=0.04 ) . There were three major complications of thrombosis or bleeding , all occurring in the PM arm . All patients who completed SM preferred to continue with that strategy . CONCLUSIONS SM was not significantly better than PM in maintaining therapeutic anticoagulation . SM was feasible and appeared safe in the present study population", "This article concerning the pharmacokinetics and pharmacodynamics of vitamin K antagonists ( VKAs ) is part of the American College of Chest Physicians Evidence -Based Clinical Practice Guidelines ( 8th Edition ) . It describes the antithrombotic effect of the VKAs , the monitoring of anticoagulation intensity , and the clinical applications of VKA therapy and provides specific management recommendations . Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh the risks , burdens , and costs . Grade 2 recommendations suggest that the individual patient 's values may lead to different choices . ( For a full underst and ing of the grading , see the \" Grade s of Recommendation \" chapter by Guyatt et al , CHEST 2008 ; 133:123S-131S . ) Among the key recommendations in this article are the following : for dosing of VKAs , we recommend the initiation of oral anticoagulation therapy , with doses between 5 mg and 10 mg for the first 1 or 2 days for most individuals , with subsequent dosing based on the international normalized ratio ( INR ) response ( Grade 1B ) ; we suggest against pharmacogenetic-based dosing until r and omized data indicate that it is beneficial ( Grade 2C ) ; and in elderly and other patient subgroups who are debilitated or malnourished , we recommend a starting dose of patients with nontherapeutic INRs , with INRs above the therapeutic range , and with bleeding whether the INR is therapeutic or elevated . For the use of vitamin K to reverse a mildly elevated INR , we recommend oral rather than subcutaneous administration ( Grade 1A ) . For patients with life-threatening bleeding or intracranial hemorrhage , we recommend the use of prothrombin complex concentrates or recombinant factor VIIa to immediately reverse the INR ( Grade 1C ) . For most patients who have a lupus inhibitor , we recommend a therapeutic target INR of 2.5 ( range , 2.0 to 3.0 ) [ Grade 1A ] . We recommend that physicians who manage oral anticoagulation therapy do so in a systematic and coordinated fashion , incorporating patient education , systematic INR testing , tracking , follow-up , and good patient communication of results and dose adjustments [ Grade 1B ] . In patients who are suitably selected and trained , patient self-testing or patient self-management of dosing are effective alternative treatment models that result in improved quality of anticoagulation management , with greater time in the therapeutic range and fewer adverse events . Patient self-monitoring or self-management , however , is a choice made by patients and physicians that depends on many factors . We suggest that such therapeutic management be implemented where suitable ( Grade 2B )", "INR self-management can reduce severe thromboembolic and hemorrhagic complications following mechanical heart valve replacement . Beginning anticoagulation therapy immediately in the postoperative period further reduces anticoagulant-induced complications . Data were collected from the first 600 surviving patients ( from a total study sample of 1200 patients ) who completed follow-up of at least 2 years . Patients were r and omly divided into a self-management group and a control group . INR self-management reduced severe hemorrhagic and thromboembolic complications ( P=0.018 ) . Nearly 80 % of INR values recorded by patients themselves , regardless of educational level , were within the target therapeutic range of INR 2.5–4.5 , compared with 62 % of INR values monitored by family practitioners . Only 8.3 % of patients trained in self-management immediately after surgery were unable to continue with INR self-management . The results differed slightly between patient groups with different levels of education . We conclude that all patients for whom anticoagulation is indicated are c and i date s for INR self-management regardless of education level", "BACKGROUND There is growing evidence that better outcomes are achieved when anticoagulation is managed by anticoagulation clinics rather than by family physicians . We carried out a r and omized controlled trial to evaluate these 2 models of anticoagulant care . METHODS We r and omly allocated patients who were expected to require warfarin sodium for 3 months either to anticoagulation clinics located in 3 Canadian tertiary hospitals or to their family physician practice s. We evaluated the quality of oral anticoagulant management by comparing the proportion of time that the international normalized ratio ( INR ) of patients receiving warfarin sodium was within the target therapeutic range + /- 0.2 INR units ( exp and ed therapeutic range ) while they were managed in anticoagulation clinics as opposed to family physicians ' care over 3 months . We measured the rates of thromboembolic and major hemorrhagic events and patient satisfaction in the 2 groups . RESULTS Of the 221 patients enrolled , 112 were r and omly assigned to anticoagulation clinics and 109 to family physicians . The INR values of patients who were managed by anticoagulation clinics were within the exp and ed therapeutic range 82 % of the time versus 76 % of the time for those managed by family physicians ( p = 0.034 ) . High-risk INR values ( defined as being 5.0 ) were more commonly observed in patients managed by family physicians ( 40 % ) than in patients managed by anticoagulation clinics ( 30 % , p = 0.005 ) . More INR measurements were performed by family physicians than by anticoagulation clinics ( 13 v. 11 , p = 0.001 ) . Major bleeding events ( 2 [ 2 % ] v. 1 [ 1 % ] ) , thromboembolic events ( 1 [ 1 % ] v. 2 [ 2 % ] ) and deaths ( 5 [ 4 % ] v. 6 [ 6 % ] ) occurred at a similar frequency in the anticoagulation clinic and family physician groups respectively . Of the 170 ( 77 % ) patients who completed the patient satisfaction question naire , more were satisfied when their anticoagulant management was managed through anticoagulation clinics than by their family physicians ( p = 0.001 ) . INTERPRETATION Anticoagulation clinics provided better oral anticoagulant management than family physicians , but the differences were relatively modest", "Background : Anticoagulation ( AC ) with warfarin reduces the risk of thromboembolism ( TE ) in a variety of applications , yet despite compelling evidence of the value and importance of high quality AC , warfarin remains underused , and dosing is often suboptimal . Approaches to improve AC quality include ( 1 ) an AC service ( ACS ) , which allows the physician to delegate day-to-day details of AC management to another provider dedicated to AC care , and ( 2 ) incorporating into the treatment plan patient self-testing ( PST ) under which , after completing a training program , patients perform their own blood testing ( typically , using a finger-stick blood analyzer ) , have dosage adjustments guided by a st and ard protocol , and forward test results , dosing and other information to the provider . Studies have suggested that PST can improve the quality of AC and perhaps lower TE and bleed rates . The purpose of Department of Veterans Affairs ( VA ) Cooperative Studies Program ( CSP ) # 481 , “ The Home INR Study ” ( THINRS ) is to compare AC management with frequent PST using a home monitoring device to high quality AC management ( HQACM ) implemented by an ACS with conventional monitoring of prothrombin time by international normalized ratio ( INR ) on major health outcomes . PST in THINRS involves use of an INR monitoring device that is FDA approved for home use . Study design : Sites are VA Medical Centers where the ACS has an active roster of more than 400 patients . THINRS includes patients with atrial fibrillation ( AF ) and /or mechanical heart valve ( MHV ) expected to be anticoagulated indefinitely . THINRS has two parts . In Part 1 , c and i date s for PST are evaluated for 2 to 4 weeks for their ability to use home monitoring devices . In Part 2 , individuals capable of performing PST are r and omized to ( 1 ) HQACM with testing every 4 weeks and as indicated for out of range values , medication/ clinical changes , or ( 2 ) PST with testing every week and as indicated for out of range values , medication/ clinical changes . The primary outcome measure is event rates , defined as the percent of patients who have a stroke , major bleed , or die . Secondary outcomes include total time in range ( TTR ) , other events ( myocardial infa rct ion ( MI ) , non-stroke TE , minor bleeds ) , competence and compliance with PST , satisfaction with AC , AC associated quality of life ( QOL ) , and cost-effectiveness . To assess the effect of PST frequency on TTR and other outcomes , at selected sites patients r and omized to perform PST are assigned one of three test frequencies ( weekly , twice weekly , or once every four weeks )", "Dem and for anticoagulation management is increasing due to an expansion of clinical indications for therapy . One possible model of care to meet dem and is patient self‐management ( PSM ) , beneficial to patients who need control over their condition . This study aim ed to determine the cost and cost‐effectiveness of PSM of anticoagulation compared with routine clinic‐based care for patients receiving long‐term anticoagulation . A cost – utility analysis was conducted alongside a r and omised controlled trial ; 617 patients were recruited and followed up for 12 months . There was no significant difference in mean quality ‐adjusted life years ( QALYs ) between groups – after adjusting for baseline , the mean difference in QALYs was 0·009 ( 95 % CI , −0·012 to 0·030 ) . Overall mean healthcare costs in the PSM arm were significantly higher at £ 417 ( CI £ 394–£442 ) compared with £ 122 ( CI £ 103–£144 ) in the control arm . Therefore , using a formal cost‐effectiveness analysis , PSM of anticoagulation does not appear to be cost‐effective . However , PSM may have other benefits in relieving pressure on traditional clinic‐based care , and the cost‐effectiveness of this model of care for some subgroups of anticoagulation patients needs to be explored further", "Oral anticoagulant therapy requires frequent laboratory controls of its intensity to assure therapeutic efficacy and to prevent potentially life threatening adverse events . It is generally assumed , that increasing the frequency of testing would lead to a better control of anticoagulation . We tested this hypothesis in a prospect i ve controlled trial comparing weekly self-testing and self-dosing ( self management ) with the st and ard-management of these patients in an anticoagulation clinic . Only patients with stable anticoagulation were included into the study . We recorded 2733 weekly determinations of the intensity of anticoagulation ( INR ) in 49 patients on self-testing and self-dosing and 539 determinations of the INR in 53 patients on st and ard-management . Two intensities of anticoagulation were used in each group : a target INR of 3.5 for patients with artificial heart valves ( target range : 2.5 - 4.5 ) and a target INR 2.5 ( target range : 2.0 - 3.0 ) for patients with atrial fibrillation or venous thromboembolism . The deviation from the target INR , the fraction of INR determinations within the preset therapeutic range and the difference between the target INR and the actually achieved mean INR were the three major endpoints of the study . The mean deviation from the target INR was smaller in the groups of patients on self-management compared to the patients on st and ard-management . Individual deviations were significantly ( p Patients on weekly self-testing and self-dosing had more INR values within the therapeutic range than patients on st and ard-management ( 86.2 % vs. 80.1 % at INR range 2.5 - 4.5 ; 82.2 vs. 68.9 at INR range 2.0 - 3.0 ) . The achieved mean INR was almost identical with the target INR in the patients on self-management but was significantly ( p INR in the high intensity anticoagulation group on st and ard-management ( target INR:3.5 ; achieved mean INR : 3.19 ; CI 0.95 : 3.05 - 3.34 ) . Our data show , that weekly self-testing and self-dosing leads to a better control of anticoagulation than st and ard treatment in an anticoagulation clinic", "BACKGROUND Severe thromboembolic and hemorrhagic complications after mechanical heart valve replacement essentially depend on the intensity of oral anticoagulation and the fluctuation of individual international normalized ratio ( INR ) values . METHODS After heart valve replacement with Medtronic Hall , St. Jude Medical , and CarboMedics implants , patients were r and omly divided into two groups , one controlling INR values at home , the other being monitored by family practitioners . RESULTS Almost 80 % of the INR values recorded by patients at home were within the stipulated therapeutic range , INR 2.5 to 4.5 , compared with just 62 % of INR values recorded by family practitioners . The overall complication rate ( hemorrhages and thromboembolic events ) of the self-management group was significantly ( p quality of ongoing oral anticoagulation could be shown . Starting this form of therapeutic control early after mechanical heart valve replacement appears to effect a further reduction in anticoagulant-induced complications", "BACKGROUND Several studies have demonstrated that patient self-management of oral anticoagulant therapy ( OAT ) can improve treatment quality . However , most of these studies were not conducted within a specialized anticoagulation care system . The objective of the present study was to determine whether patient self-management of OAT improves the quality of care delivered by anticoagulation clinics . METHODS In this r and omized study by 2 Dutch anticoagulation clinics 341 patients aged between 18 and 75 years and receiving long-term OAT were divided into 4 groups : an existing routine care group of patients untrained in self-management ; a routine care group of trained patients ; a group managed weekly at an anticoagulation clinic where international normalized ratios were measured by trained patients ; and weekly patient self-management . A 2-step r and omization procedure was followed : first , a Zelen- design r and omization was performed to distribute patients ( without informing them ) to the existing care group or to receive training in self-management ; second , trained patients were r and omized to the 3 other study groups . RESULTS Only 25.6 % of invited patients agreed to participate in the training program . Patients who remained in the existing care group were within the international normalized ratio target range 63.5 % of the time . The type of coumarin taken was a major predicting factor of OAT quality . In all study groups phenprocoumon outperformed acenocoumarol by 11.6 % ( 95 % confidence interval [ CI ] , 6.6%-16.5 % ) . Weekly management with phenprocoumon led to a 6.5 % improvement ( 95 % CI , 0.0%-13.1 % ) in time in the international normalized ratio target range when patients were managed at an anticoagulation clinic and to an 8.7 % improvement ( 95 % CI , 1.6%-15.9 % ) when patients were self-managed . Weekly management with acenocoumarol did not improve the quality of OAT . CONCLUSION With selected patients , the quality of OAT obtained through patient self-management is at least as high as that delivered by specialized physicians at anticoagulation clinics . Weekly management of OAT with long-acting phenprocoumon has to be preferred at anticoagulation clinics or , where possible , through patient self-management", "Several studies suggest that patient self‐management ( PSM ) may improve the quality of oral anticoagulation therapy as measured by time spent within the international normalised ratio ( INR ) target range . We performed a prospect i ve r and omised control trial to determine whether the improvement in quality of treatment afforded by PSM is greater than that achieved by patient self‐testing ( PST ) alone . A total of 104 of 800 eligible patients aged 22–88 years ( median = 59·8 ) , attending our hospital anticoagulant clinic and receiving long‐term warfarin for > 8 months agreed to participate . Patients were r and omised to PSM ( n = 55 ) or PST ( n = 49 ) . Both groups measured their INR using the CoaguChek S every 2 weeks or more frequently if required , for a period of 6 months . Seventy‐seven of 104 ( 74 % ) patients completed the study ( PSM = 41 and PST = 36 ) . The ‘ drop out ’ rates for both groups were similar . There was no significant difference between the percentage time in target therapeutic range for PSM ( 69·9 % ) and PST ( 71·8 % ) . Both groups combined showed a significant improvement over the previous 6 months ( 71·0 % vs. 62·5 % ; P = 0·04 ) . Changes in time within the therapeutic range in individual patients ( + 5·86 ) also showed a significant difference . The quality of warfarin control in both PST and PSM may be superior to that achieved by conventional management in a specialised hospital anticoagulation clinic", "BACKGROUND Patients who are receiving warfarin therapy require frequent blood testing to monitor the intensity of anticoagulation . Although previous studies suggest that capillary blood monitoring of the international normalize ratio ( INR ) is rapid and reliable , patient preferences for the method of blood drawing have not been investigated . METHODS We performed a r and omized controlled trial of patients attending an anticoagulation clinic in which patients were r and omly allocated to undergo capillary or venous INR monitoring . Patient satisfaction with the outpatient visit , pain associated with blood drawing , and time spent in the clinic were assessed for each patient . RESULTS Sixty patients were studied . Using a 10-point visual analogue scale to quantify patient satisfaction ( 0-very satisfied ; 10-very dissatisfied ) , patients expressed a strong preference for capillary INR monitoring over venous INR monitoring ( 1.64 vs. 4.45 ; P analogue scale to quantify pain with blood sampling ( 0-no pain ; 10-very painful ) , patients who underwent capillary INR testing had less pain than venous INR testing ( 0.83 vs. 2.23 ; P spent , on average , 33 fewer minutes in the clinic with capillary INR testing than venous INR testing ( P capillary blood testing , using a portable monitor , for the management of patients in outpatient anticoagulation clinics", "R and omized trials have indicated that well-managed anticoagulation with warfarin could prevent more than half of the strokes related to atrial fibrillation . However , many patients with atrial fibrillation who are eligible for this therapy either do not receive it or are not maintained within an optimal prothrombin time-international normalized ratio ( INR ) range . We sought to determine whether an anticoagulation service within a managed care organization would be a feasible alternative for providing anticoagulation care . We performed a multi-site r and omized trial in six large managed care organizations in the United States . Subjects were aged 65 years or older and had nonvalvular atrial fibrillation . At each site , physician practice s were divided into two geographically defined practice clusters ; each site was r and omly assigned to have one intervention and one control cluster . The intervention cluster received an anticoagulation service that satisfied specifications for high- quality anticoagulation care and was coordinated through the managed care organization . Control clusters continued with their usual provider-based care . We measured the proportion of time that warfarin-treated patients in each of the clusters ( intervention and control ) were in the target range for the INR at baseline , and again during a follow-up period . Five of the six selected sites succeeded at developing an anticoagulation service . Patients in the intervention and control clusters had similar demographic characteristics , contraindications to warfarin , and risk factors for stroke . Among patients ( n = 144 in the intervention clusters ; n = 118 in the control clusters ) for whom data were available during the baseline and follow-up periods , the changes in percentages of time in the target range were similar for those in the intervention clusters ( baseline : 47.7 % ; follow-up : 55.6 % ) and in the control clusters ( baseline : 49.1 % ; follow-up : 52.3 % ; intervention effect : 5 % ; 95 % confidence interval : -5 % to 14 % ; P = 0.32 ) . Although it was feasible in a managed care organization to implement anticoagulation services that were tailored to local circumstances , provision of this service did not improve anticoagulation care compared with usual care . The effect of the anticoagulation service was limited by the utilization of the service , the degree to which the referring physician supports strict adherence to recommended target ranges for the INR , and the ability of the anticoagulation service to identify and to respond to out-of-range values promptly", "Der Großteil der Patienten mit Vorhofflimmern ist durch ein thromboembolisches Ereignis gefährdet . Die Komplikationsrate kann durch eine effiziente Antikoagulation um zwei Drittel reduziert werden . Ob die Qualität der Therapieüberwachung durch das Selbstmanagement bei Patienten mit Vorhofflimmern ( SMAAF-Studie ) i m Vergleich zur herkömmlichen bei Hausarzt betreuten Patienten verbessert werden kann , war Gegenst and dieser prospektiven Multicenter- Studie . Bei Eignung zum Selbstmanagement sollten 2 000 Patienten in die beiden Studienarme r and omisiert werden . I m Untersuchungszeitraum von 12/99 bis 07/01 gaben lediglich 202 Patienten ( 64,3±9,2 Jahre , 69,3 % Männer ) ihr Einverständnis . Bei vorzeitigem Studienabbruch aufgrund zu niedriger Patientenzahl beschränkt sich der Gruppenvergleich auf die Auswertung gemessener INR-Werte mittels zweiseitigem t-Test . Von den 202 eingeschlossenen Patienten wurden 101 der Selbstmanagement-Gruppe ( 64,6±9,6 Jahre , 71,4 % Männer ) und 101 ( 64,1±8,9 Jahre , 61,4 % Männer , n.s . ) der Hausarztgruppe zugeordnet . Die Gesamtzahl der INR-Messungen betrug 2 865 , wobei 2 072 auf Patienten i m Selbstmanagement und 793 auf die Hausarztgruppe entfielen . Die Werte lagen bei Patienten i m Selbstmanagement mit 67,8 % i m Vergleich zur Hausarztgruppe mit 58,5 % signifikant häufiger ( p=0,0061 ) i m Zielbereich . Bezüglich der Verweildauer i m therapeutischen Bereich best and zwar ein Trend zugunsten der Selbstmanagement-Gruppe , jedoch kein signifikanter Unterschied ( 178,8±126 Tage vs. 155,9±118,4 Tage ) . In der Selbstmanagement- Gruppe traten zwei schwere Blutungen , in der Hausarztgruppe ein thromboembolisches Ereignis auf . Die Therapieüberwachung der oralen Antikoagulation durch das INR-Selbstmanagement ist bei Patienten mit Vorhofflimmern der Betreuung durch den Hausarzt nicht unterlegen . Most patients with atrial fibrillation are at risk of suffering thromboembolic events . This risk can be reduced by twothirds by efficient anticoagulation . This prospect i ve multi-center trial investigated whether the quality of treatment can be improved by self-management in patients with atrial fibrillations ( SMAAF Study ) compared to conventional patient management by the family doctor . Two thous and patients suitable for self-manage- ment were to be r and omized into the two arms of the study . In the period of investigation from December 1999 to July 2001 , only 202 patients ( 64.3±9.2 years , 69.3 % men ) consented to participate . The study was discontinued prematurely since the number of patients was too low . As a consequence , the group comparison is confined to the evaluation of the INR values measured using the two-tailed t test . Of the 202 patients included , 101 were assigned to the self-management group ( 64.6±9.6 years , 71.4 % men ) and 101 ( 64.1±8.9 years , 61.4 % men , n.s . ) were assigned to the group managed by the family doctor . The total number of INR measurements was 2 865 . This comprised 2 072 measurements in patients under self-management and 793 in the family doctor group . The values were within the target range significantly more frequently ( p=0.0061 ) in patients under self-management ( 67.8 % ) as compared to the family doctor group ( 58.5 % ) . There was a trend with regard to the time within target range , but the difference was not significant ( 178.8±126 days as compared to 155.9±118.4 days ) . In the self-management group , there were two severe hemorrhages , and there was one thromboembolic event in the family doctor group . Management of oral anticoagulation by INR self-management in patients with atrial fibrillation is not inferior to conventional care", "BACKGROUND To avert major hemorrhage , physicians need to know the lowest intensity of anticoagulation that is effective in preventing stroke in patients with atrial fibrillation . Since the low rate of stroke has made it difficult to perform prospect i ve studies to resolve this issue , we conducted a case-control study . METHODS We studied 74 consecutive patients with atrial fibrillation who were admitted to our hospital from 1989 through 1994 after having an ischemic stroke while taking warfarin . For each patient with stroke , three controls with nonrheumatic atrial fibrillation who were treated as out patients were r and omly selected from the 1994 registry of the anticoagulant-therapy unit ( 222 controls ) . We used the international normalized ratio ( INR ) to measure the intensity of anticoagulation . For the patients with stroke , we used INR at admission ; for the controls , we selected the INR that was measured closest to the month and day of the matched case patient 's hospital admission . RESULTS The risk of stroke rose steeply at INRs below 2.0 . At an INR of 1.7 , the adjusted odds ratio for stroke , as compared with the risk at an INR of 2.0 , was 2.0 ( 95 percent confidence interval , 1.6 to 2.4 ) ; at an INR of 1.5 , it was 3.3 ( 95 percent confidence interval , 2.4 to 4.6 ) ; and at an INR of 1.3 , it was 6.0 ( 95 percent confidence interval , 3.6 to 9.8 ) . Other independent risk factors were previous stroke ( odds ratio , 10.4 ; 95 percent confidence interval , 4.4 to 24.5 ) , diabetes mellitus ( odds ratio , 2.95 ; 95 percent confidence interval , 1.3 to 6.5 ) , hypertension ( odds ratio , 2.5 ; 95 percent confidence interval , 1.1 to 5.7 ) , and current smoking ( odds ratio , 5.7 ; 95 percent confidence interval , 1.4 to 24.0 ) . CONCLUSIONS Among patients with atrial fibrillation , anticoagulant prophylaxis is effective at INRs of 2.0 or greater . Since previous studies have indicated that the risk of hemorrhage rises rapidly at INRs greater than 4.0 to 5.0 , tight control of anticoagulant therapy to maintain the INR between 2.0 and 3.0 is a better strategy than targeting lower , less effective levels of anticoagulation", "Background and objective Internet-based disease management programs have the potential to improve patient care . The objective of this study was to determine whether an interactive , internet-based system enabling supervised , patient self-management of oral anticoagulant therapy provided management comparable to an established anticoagulation clinic . Patients / methods Sixty patients receiving chronic oral anticoagulant therapy who had access to the internet and a printer , were enrolled into this prospect i ve , single-group , before-after study from a single clinic and managed between March 2002 and January 2003 . Patients learned how to use a home prothrombin time monitor and how to access the system through the internet . Patients used the system for six months , with daily review by the supervising physician . The primary outcome variable was the difference in time in therapeutic range prior to and following introduction of internet-supervised patient self-management . Results The mean time in therapeutic range increased from 63 % in the anticoagulation clinic ( control period ) to 74.4 % during internet-supervised patient self-management ( study period ) . The mean difference score between control and study periods was 11.4 % ( P = 0.004 , 95 % confidence interval 5.5–17.3 % ) . There were no hemorrhagic or thromboembolic complications . Conclusions This novel approach of internet-supervised patient self-management improved time in therapeutic range compared to an anticoagulation clinic . This is the first demonstration of an internet-based expert system enabling remote and effective management of patients on oral anticoagulants . Expert systems may be applicable for management of other chronic diseases", "STUDY OBJECTIVE To evaluate the efficacy and accuracy of monitoring prothrombin times at home . DESIGN R and omized , prospect i ve cohort study . SETTING Out patients discharged from a university hospital or a community hospital . PATIENTS Fifty patients started on warfarin for the first time who demonstrated an ability to use the monitor and who had not achieved a stable response to warfarin in the hospital . INTERVENTION Oral anticoagulation therapy managed using a portable prothrombin time monitor compared with specialized anticoagulation clinic care . MEASUREMENTS AND MAIN RESULTS In the 46 patients who completed the 8-week study , the median percentage of time that patients in the home-monitor group ( n = 23 ) were within a range equal to the target prothrombin ratio + /- 0.3 , but always above 1.25 , was 93 % , compared with 75 % for patients in the clinic group ( n = 23 ) ( P = 0.003 ) . There was no significant difference between groups in the percentage of time above the therapeutic range ; however , the percentage of time that patients were subtherapeutic was significantly greater in the clinic group ( P less than 0.001 ) . There were no major thromboembolic or hemorrhagic complications in either group . Differences between home monitor measurements and corresponding clinical laboratory measurements using blood sample s drawn within 4 hours of the home test were comparable to differences observed between measurements using two different clinical laboratory instruments . CONCLUSIONS Use of a portable prothrombin time monitor by patients at home is feasible and provides accurate measurements . Patients doing home monitoring achieve superior anticoagulation control compared with those receiving st and ard anticoagulation clinic care", "Context Although many out patients require oral anticoagulation , the optimal management of outpatient anticoagulation remains uncertain . Studies have demonstrated the feasibility of patient self-management using portable coagulometers , but the studies that compared patient outcomes with self-management and those with conventional management in an anticoagulation clinic did not find a better outcome with self-management . Contribution In this r and omized , controlled trial of 737 patients , patients assigned to self-management of anticoagulation achieved a similar level of control and had fewer adverse events than patients assigned to conventional management . Implication s Health care providers should begin to implement patient self-management of oral anticoagulation with portable coagulometers in mainstream practice . The Editors Indications for oral anticoagulant treatment to prevent thromboembolic disease have increased in recent years ( 1 ) . Prothrombin times must be monitored frequently in patients taking oral anticoagulants to determine the safest dose and to minimize the risk for complications . The clinical management of oral anticoagulant treatment improved greatly after the international normalized ratio ( INR ) was introduced as a measurement of anticoagulation intensity ( 1 ) . The establishment of accurate therapeutic INR ranges was also beneficial . Target ranges include the safest INR values that carry the lowest risk for hemorrhagic or thromboembolic complications ( 2 ) . Despite these improvements , however , serious complications are still associated with oral anticoagulant treatment ( 3 , 4 ) , and management by specialized staff at anticoagulation clinics seems to be safer than other clinical strategies in terms of numbers of complications ( 5 - 7 ) . Currently , portable coagulometers are available for determining INR easily and reliably ( 8) . This technology provides interesting clinical models for the control of oral anticoagulant treatment , the most promising of which are patient self-testing and patient self-management . For patient self-testing , patients measure INRs themselves and ask their referring physicians for the proper anticoagulant dose . Patient self-management assumes that patients will adjust their own doses and is the most autonomous strategy . Several published studies have compared these strategies with usual care ( that is , monitoring of oral anticoagulant treatment by practitioners ) ( 9 - 13 ) or with specialized anticoagulation clinics ( 14 - 18 ) . Although these studies showed that both patient self-testing and patient self-management are feasible , their sample s were relatively small ( 9 , 11 , 13 , 14 - 18 ) or included selected patients with mechanical valve prostheses ( 10 ) or patients older than 65 years of age ( 12 ) . In general , previous studies indicate that patient self-management may be superior to management by general practitioners or anticoagulation clinics in quality of INR control ( 10 - 18 ) . In addition , Krtke and Krfer ( 10 ) , Beyth and associates ( 12 ) , and Sawicki ( 13 ) reported a decrease in major complications among self-managed patients compared with patients managed by general practitioners . To date , no published data have suggested a better clinical outcome ( decrease in associated complications ) with patient self-management than with specialized management at an anticoagulation clinic ( 5 , 19 ) . We performed a r and omized , controlled trial to directly compare self-management of oral anticoagulant treatment , as evaluated in terms of efficacy and safety in unselected patients , with management in an anticoagulation clinic . Methods Study Design The Alternative Control of Oral Anticoagulant Treatment ( ACOA ) trial is a single-center , central ly r and omized , controlled study that was performed at Hospital de la Santa Creu i Sant Pau , Barcelona , Spain , from January 2001 to July 2002 . The hematologists who manage our anticoagulation clinic use a homogeneous dosing protocol and st and ard protocol s to manage situations that increase clinical risk . The clinical staff includes trained nurses . Computers control the clinical data and INR records , ensuring excellent follow-up . Patients and their relatives receive basic education at the beginning of oral anticoagulant treatment , including information on the main characteristics of oral anticoagulants , potential risks , rationale for periodic monitoring , and drug interactions . Samsa and Matchar ( 20 ) recommended that these characteristics be used to provide an appropriate control group in a trial on patient self-management . The institutional review board of our hospital approved the study . Recruitment Phase The recruitment phase began with computerized r and om selection of 1500 patients from the more than 5000 who were receiving oral anticoagulant treatment controlled in our hospital . We included any ambulatory patient 18 years of age or older who had been receiving long-term anticoagulant therapy for at least 3 months before entering the study . We excluded patients who were younger than 18 years of age , who had a severe physical or mental illness without a responsible caregiver , or who were of foreign origin and were unable to underst and Spanish . Once the patient ( or his or her caregiver ) agreed to participate , written informed consent was obtained . Next , central ized telephone r and omization assigned the patient to the experimental group ( patient self-management ) or to the control group ( conventional management ) . The allocation sequence was generated at the hospital 's epidemiology department , and the sequence of r and omization was concealed until the patient was assigned to a group . To facilitate comparability between study groups , this r and omization was stratified according to sex , age ( 70 years of age or oral anticoagulant treatment ( 4 groups ) . Members of our anticoagulation clinic enrolled participants and assigned them to groups . Baseline data included demographic details , clinical information on associated risk factors , other medications , previous length of anticoagulant therapy , bleeding or thromboembolic complications during oral anticoagulant treatment , and target INR range . Follow-up for patients assigned to the conventional management group was done immediately . Patients in the self-management group received a training course first , and follow-up was not performed until the nurse teaching the course judged that the patients had acquired a minimum of expertise in self-management . Training Course An educational program was design ed to optimize the number of patients able to underst and and safely perform self-management ( Appendix ) . It was similar to the German program developed by Sawicki ( 13 ) but was demographically adapted to the characteristics of the Spanish population , considering differences in daily schedules , diet , educational level , and other idiosyncratic factors . The program consisted of 2 sessions of 2 hours each on consecutive days . A specially trained nurse was responsible for teaching the patients in small , organized groups . The lessons included basic theoretical and practical concepts involving the use of a coagulometer , interpretation of INR , and adjustment of dose . The concepts of target range and dose modification were emphasized when necessary . A simple card system was design ed to help the patient select the correct dose . For each target range , a specific card was provided . Patients were taught to use the portable coagulometer CoaguChek S ( Roche Diagnostics , Mannheim , Germany ) with the appropriate reagent strips . Follow-up Phase Normally , the patients in the conventional management group visited our hospital every 4 weeks to check their INRs . When the INR result was out of target range , our dosing protocol indicated that we should advance the next appointment for INR testing to 1 or 2 weeks . International normalized ratio was determined by means of a st and ard KC 10 coagulometer ( Amelung , Lemgo , Germany ) . As a thromboplastin , we used Thromborel S ( Behring , Marburg , Germany ) . A hematologist experienced in oral anticoagulation management adjusted the dose and made the appointment for the next INR test . Patients in the self-management group performed the INR tests at home once per week using the CoaguChek S kit . They determined the appropriate dose of oral anticoagulant and the time of the next INR test . All of the INR results in both groups were entered into a computer ( in the central system of our anticoagulation clinic or in the portable coagulometers ) to facilitate data management . Patients in both groups were interviewed monthly by telephone to record any complications or changes in their health status . For the conventional management group , these interviews were done approximately midway between hospital visits . The questions addressed minor or major bleeding , thromboembolic events , episodic diseases , changes in long-term medications , and hospital stays . Associated complications were diagnosed and evaluated by a third physician who was not involved in the trial and was unaware of patients ' study group . St and ard criteria were used to diagnose any thromboembolic complications . Transient ischemic attack was diagnosed clinical ly by a neurologist , and superficial thrombophlebitis was diagnosed clinical ly by an angiologist . To diagnose stroke , arterial embolism , venous thromboembolism , pulmonary embolism , or valve thrombosis , we used widely accepted methods ( computed tomography or magnetic nuclear resonance imaging , angiography , surgical diagnosis , Doppler ultrasonography , phlebography , lung angiography or ventilation-perfusion lung scanning , cardiac ultrasonography , or fluoroscopy ) . All thromboembolic complications were considered major events . Life-threatening bleeding or bleeding requiring transfusion or hospital admission was considered a major event . Any other bleeding was considered a minor event . Statistical Analysis Study outcomes were evaluated on an intention-to-treat basis and also on an on-treatment basis .", "Summary . The success in achieving therapeutic international normalized ratio ( INR ) targets in the control of warfarin using a whole‐blood point‐of‐care testing ( POCT ) monitor ( CoaguChek ) in a community clinic was compared with hospital laboratory coagulometer prothrombin time ( PT ) testing in a r and omized crossover study . Forty‐six patients were r and omized into two groups . At each visit , capillary blood was taken for the POCT monitor and venous blood for the laboratory coagulometer . In Group 1 , for 6 months , dosage was based on the CoaguChek and for the second 6 months on the coagulometer . In the second group , the order was reversed . Dosages were determined using the dawn ac computer programme . Success was assessed by the percentage of time patients were maintained within the INR targets . Agreement between laboratory and monitor INR , and patient satisfaction were also assessed . Results with the POCT monitor compared well with the hospital coagulometer . Time in INR target range between the groups was similar , with 60·9 % on the POCT monitor and 59·3 % with the laboratory coagulometer in Group 1 and in Group 2 , respectively , 64·3 % and 63·4 % with no significant difference in mean INR . An INR above 4·0 gave some discrepant results . International Sensitivity Index calibrations of the two test systems indicated that the INRs were dependable . Patient question naires showed greater satisfaction with community POCT monitoring", "BACKGROUND The efficacy of self-managed oral anticoagulant therapy has been addressed in few r and omized , controlled trials , which have provided inconsistent results . The aim of this study was to compare the quality of self-managed oral anticoagulant therapy with conventional management . METHODS This was a pragmatic , open-label , r and omized , controlled trial where 100 patients receiving long-term oral anticoagulant therapy referred to a Danish clinic for self-management was r and omized to either self-management of oral anticoagulant therapy ( including a teaching program of self-management followed by 6 months of self-management ) or 6 months of conventional management . The primary endpoint was an intention-to-treat analysis of a composite score combining the variance ( median square of the st and ard deviation ) of the International Normalized Ratio ( INR ) value ( using a blinded control sample analyzed monthly by a reference laboratory ) , death , major complications , or discontinuation from the study . Secondary endpoints - assessed in per- protocol analyses - were the variance of the INR value ( using the blinded control sample ) and time within therapeutic INR target range using the st and ard INR values from the coagulometer and laboratory measurement . RESULTS There was no significant difference in the primary endpoint between the self-management and conventional management groups ( composite score 0.16 vs. 0.24 , respectively , p=0.09 ) . Self-management was significantly better ( 0.16 vs. 0.24 , p=0.003 ) with regard to the variance in a per- protocol analysis . The difference in time within therapeutic INR target range was not significantly better ( 78.7 % vs. 68.9 % , p=0.14 ) using self-management . CONCLUSION The quality of self-management of oral anticoagulant therapy is at least as good as that provided by conventional management", " Of 125 patients aged 65 years or over , with atrial fibrillation taking warfarin for at least 12 months , with a st and ard deviation ( SD ) of prothrombin time , expressed as the International Normalized Ratio ( INR ) > 0·5 over the previous 6 months , 40 were r and omized to continue with usual clinic care and 85 to receive education about warfarin . Of these , 44 were r and omized to self‐monitor their INR and 41 returned to clinic . Compared with the previous 6 months there was a significant increase in percentage time within the therapeutic range for the 6 months following education [ 61·1 vs. 70·4 ; mean difference 8·8 ; 95 % confidence interval ( CI ) : −0·2–17·8 ; P = 0·054 ] and following education and self‐monitoring ( 57 vs. 71·1 ; mean difference 14·1 ; 95 % CI : 6·7–21·5 ; P , the INR SD fell by 0·24 ( P to education and self‐monitoring , 0·26 ( P receiving education alone and 0·16 ( P = 0·003 ) in the control group . Inter‐group differences were not statistically significant ( intervention groups 0·26 ± 0·30 vs. control 0·16 ± 0·3 , P = 0·10 ) . Quality ‐of‐life measurements and health beliefs about warfarin were unchanged ( apart from emotional role limitation ) with education or education and self‐monitoring . Patient education regarding anticoagulation therapy could be a cost‐effective initiative and is worthy of further study", "BACKGROUND This study was conducted to assess the ability of patients receiving heart valve replacements to practice self-managed anticoagulation using a portable coagulometer . METHODS We carried out a prospect i ve , r and omized trial , comparing self-managed anticoagulation with conventional management . Patients practicing self-managed anticoagulation ( 51 patients ) did so at home , measuring their international normalized ratio and then deciding on their dosage of warfarin , while conventionally controlled patients ( n = 49 ) attended hospital clinics or were managed by their family physicians . RESULTS We successfully trained 41 of 44 patients who agreed to self-manage their anticoagulant therapy ; 34 of the 41 managed their own anticoagulation at home for 2 years . Their control , assessed by a number of tests in range ( 67.6 % versus 58.0 % ) and time in therapeutic range ( 76.5 % versus 63.8 % ) , was significantly better than that for the group managed conventionally ( p mortality or morbidity between the two groups . CONCLUSIONS Self-managed anticoagulation is a reliable , easily learned method of controlling anticoagulation , and it is suitable for approximately two thirds of patients , with excellent results", "Bleeding is the major side effect of warfarin and is a major deterrent to its use , especially in older patients . Older people are widely thought to be at increased risk for warfarin-related bleeding ( 1 - 8 ) , and they are less likely to be treated with warfarin , even when it has been proven efficacious , in part because of concern about risk for bleeding ( 9 - 13 ) . Efforts that reduce the frequency of major warfarin-related bleeding not only will increase the net benefit of therapy but also will facilitate more appropriate and widespread use of warfarin therapy in older patients . Methods for identifying patients at highest risk for bleeding have recently advanced ( 5 - 7 , 14 - 21 ) , and experience with specialized programs that coordinate the management of anticoagulant therapy suggests that clinical outcomes may be improved ( 6 , 14 , 18 , 22 - 27 ) . However , there is little controlled or experimental evidence on how to optimize management of anticoagulant therapy in older patients and prevent bleeding . We developed a multicomponent comprehensive program for management of warfarin therapy aim ed at improving control of the anticoagulant effect and reducing events ( such as use of an interacting medicine ) that might precipitate bleeding . We hypothesized that this intervention would be acceptable to most elderly persons starting warfarin therapy and would reduce the frequency of warfarin-related major bleeding . Methods Patients Patients hospitalized at University Hospitals of Clevel and , a 900-bed teaching hospital , between September 1992 and October 1995 who were 65 years of age or older and were receiving 10 000 units or more of intravenous unfractionated heparin every 24 hours were screened daily . Of these patients , we identified 426 persons who were 65 years of age or older , who resided in Cuyahoga County , Ohio , and for whom treatment with warfarin was planned for 10 or more days ( Figure 1 ) . Patients were excluded if they had been treated with warfarin at any time during the previous 6 months , were admitted from a nursing home , were enrolled in another clinical trial , were too ill to give consent and had no available surrogate , were discharged prematurely , or did not speak English ; if their private physician refused to participate ; or if no r and om allocation was taking place ( for example , during vacations or holidays ) . Eligible patients who were enrolled did not differ significantly from those who were not enrolled with regard to age , ethnicity , sex , or indication for therapy . Figure 1 . Eligibility and r and om assignment of patients . Patients were stratified according to their baseline risk for major bleeding by using the Outpatient Bleeding Risk Index ( 20 ) . This index includes four independent risk factors for major bleeding : age 65 years or older , history of gastrointestinal bleeding , history of stroke , and one or more of four specific comorbid conditions ( recent myocardial infa rct ion , hematocrit133 mol/L [ 1.5 mg/dL ] , or diabetes mellitus ) . Patients with one or two risk factors were classified as intermediate risk , and those with three or more risk factors were classified as high risk ; estimated frequencies of major bleeding in 6 months were 6 % and 35 % , respectively . After stratification , patients were r and omly assigned to receive usual care or intervention . Informed consent for observation and data collection was then sought from both groups , and informed consent to participate in the intervention was sought from the intervention group . This method , initially proposed by Zelen ( 28 ) , allows the study to test the effectiveness of offering the intervention rather than simply the efficacy of the intervention in patients who consent to participation before r and om assignment . The sample size was calculated to provide 80 % power and an level of 0.05 . The study protocol and informed consent procedures were approved by the hospital 's institutional review board . Intervention The intervention had two main components . The first component consisted of a guideline -based consultation that assessed the patient 's indications for therapy and potential risk factors for warfarin-related bleeding . We used this method previously to reduce the frequency of anticoagulant-related bleeding during hospitalization ( 27 ) . Specific recommendations about modifiable risk factors , such as use of nonsteroidal anti-inflammatory drugs , were made and implemented . The study investigators directed warfarin dosing and international normalized ratio ( INR ) testing after hospital discharge . The second component included patient education , coaching , and self-monitoring of prothrombin time ; this component was grounded in social learning theory ( 29 - 31 ) and experimental evidence ( 32 , 33 ) showing that increasing participation of patients in their care can improve clinical outcomes but that increasing patient knowledge alone is insufficient ( 34 , 35 ) . Patient education consisted of one-on-one teaching by a lay educator using a specifically formatted workbook for older adults to teach them about warfarin , indications for its use , drug and food interactions , and the signs and symptoms of bleeding . The lay educator review ed the workbook and was taught how to use the prothrombin time monitor by one of the authors but had no formal medical training . Coaching was aim ed to increase patients ' participation in their care and to improve information-seeking skills . Patients were trained and encouraged to communicate more effectively with physicians and other health personnel about a range of issues , such as health concerns , drug interactions , or changes in lifestyle or diet . Finally , patients were taught to self-monitor the prothrombin time by using a home portable monitor ( Coumatrak Protime Test System , Biotrack , Inc. , Mountain View , California ) . The monitor uses a fingerstick to obtain a blood sample and has well-established accuracy ( 36 - 38 ) . Patients were initially assessed , educated , and taught to use the portable monitor while hospitalized ; training lasted 30 minutes to 1 hour . They were seen daily while hospitalized , warfarin therapy was adjusted as needed , and any concerns or questions about anticoagulant therapy were addressed . Within 3 days of discharge from the hospital , the lay educator or study investigator made a home visit to assess patients ' use of the portable monitor and to check the prothrombin time . In general , patients were instructed to check their prothrombin time three times during the first week after hospital discharge , weekly for the remainder of the first month , and monthly thereafter depending on their results . Patients phoned in their results to the coach , who review ed the results with one of the investigators and provided same-day follow-up , including recommendations for dose and subsequent INR testing . Patients were instructed to call whenever they had questions or concerns about their warfarin management or possible side effects , if they were hospitalized for any reason , or if they began receiving new medications . After the 6-month intervention period , management and dosing of warfarin therapy reverted back to patients ' personal physicians . Patients assigned to usual care received medical care , including management , dosing , and medical information , according to the discretion and practice s of their personal physician . Data Collection Trained abstract ors who were not involved with the intervention component of the study collected data from the medical chart at the start of anticoagulant therapy ; at each subsequent hospitalization ; and by blinded interview at enrollment and 1 , 3 , and 6 months after enrollment and every 6 months thereafter . Data elements included demographic characteristics , clinical history including comorbid diagnoses , indications for therapy , potential risk factors for bleeding , functional status , and new illnesses or comorbid conditions that developed after enrollment . Surveillance for bleeding and thromboembolism was conducted identically in the intervention and control groups and consisted of 12 items inquiring about bleeding and thromboembolism at each follow-up interview . Whenever an event was reported , the clinical characteristics of the bleeding or thromboembolic episode were determined by review of the relevant medical record and abstract ed without identifying patient information onto a st and ard form . All date s of death were confirmed by death certificates , and all causes of death were confirmed by review of death certificates and medical records . Follow-up was complete for all patients . End Points The primary end point was the first major bleeding event during the 6-month intervention period . Using explicit criteria in the Bleeding Severity Index ( 39 ) for the amount , rate , and consequences of bleeding , we defined major bleeding as overt bleeding that led to the loss of at least 2.0 units of blood in 7 days or less or was otherwise life-threatening ( for example , intracranial bleeding ) . Bleeding was classified without information about possible risk factors or r and omization status . Two author- review ers who were blinded to group assignment adjudicated bleeding events ; their agreement was high ( statistic , 0.97 ) . Secondary outcomes were death and recurrent venous thromboembolism at 6 months ; major bleeding after 6 months ; and control of anticoagulant therapy during the first 6 months of therapy , as measured by the INR . The therapeutic range of the INR was defined as 2.5 to 3.5 for persons with mechanical heart valves and 2.0 to 3.0 for persons with all other indications ( 40 ) . Therapeutic quality control was assessed by using the patient-time approach , described by Rosendaal and colleagues ( 41 ) , for three time periods after discharge from the hospital : 0 to 1 month , 1 to 3 months , and 3 to 6 months of therapy . This approach estimates the amount of time a patient is in the therapeutic range based on the actual INRs measured , assuming a linear relationship between consecutive INRs . Patients with only one", "An ageing population and the continuing expansion of clinical indications for coumadin therapy have increased pressure on hospital anticoagulant clinics . One solution is patient self‐testing ( PST ) of the international normalized ratio ( INR ) using capillary blood sample s on point‐of‐care coagulation monitors at home . We conducted a prospect i ve study to determine whether patients can achieve accurate INR values through PST , using the CoaguChek S ( Roche Diagnostics , Lewes , UK ) . The main outcome measurements were : comparability of INR values obtained by PST and the hospital laboratory , patient acceptability as assessed by a question naire and anticoagulant control . Eighty‐four patients [ 53 men , 31 women ; median age 59 years ( range 26–83 ) ] , receiving long‐term oral anticoagulation ( warfarin ) , were recruited from our Anticoagulation Clinic . Patients were r and omized to weekly self‐testing or continuing 4‐weekly hospital laboratory monitoring of INR . Comparison of INRs ( n = 234 ) showed no significant differences between the CoaguChek ( median INR 3·02 ) and laboratory testing ( median INR 3·07 ) . There was excellent correlation between the two methods ( r = 0·95 ) , with 85 % of CoaguChek results within 0·5 INR units of the laboratory method . On four occasions , differences of > 1 unit INR were obtained , but in each case the patient 's anticoagulation was unstable ( INR > 4·5 by both methods ) and the differences in INR would not have altered patient management . 87 % of patients found self‐testing straightforward , 87 % were confident in the result they obtained and 77 % preferred self‐testing . We conclude that PST is a reliable alternative to hospital clinic attendance and is acceptable to the majority of suitably trained patients", "Although many patients with long-term oral anticoagulation ( OAC ) can manage their medication safely and reliably themselves , no study on elderly patients has as yet assessed the safety and efficacy of OAC self-management with major thromboembolic and haemorrhagic complications as primary outcomes . In this multi-centre trial , patients aged 60 years or more were r and omised into a self-management ( SMG ) ( N = 99 ) or routine care group ( RCG ) ( N = 96 ) . The primary outcome was the combined endpoint of all thromboembolic events requiring hospitalisation and all major bleeding complications . Mean follow-up was 2.9 + /- 1.2 and 3.0 + /- 1.1 years in the SMG and RCG , respectively . In intention-to-treat analysis , 12 patients in the SMG versus 22 patients in the RCG reached a primary endpoint ( hazard ratio [ HR ] : 0.50 ; 95 % confidence interval [ CI ] : 0.25 to 1.00 ; p = 0.049 ) . The post-hoc analysis on OAC treatment sensitivity supported the benefit of self-management ( HR 0.27 ; 95 % CI : 0.13 to 0.71 ; p = 0.006 ) . Fifteen patients in the SMG died during the study , but none of the deaths was directly associated with anticoagulation therapy . In the RCG , 11 patients died ; of those , three deaths were directly associated with anticoagulation therapy and there was one death of unknown cause . During follow-up , the quality of OAC control was significantly better in the SMG than in the RCG . In elderly patients , long-term self-management of oral anticoagulation is superior for the prevention of major thromboembolic and bleeding complications and for the quality of oral anticoagulation control compared to routine care for a mean follow-up period of three years", "BACKGROUND Although prosthetic valves are durable and easy to implant , the need for lifetime warfarin-based anticoagulation restricts their exclusive usage . We investigated if anticoagulation self-management improves outcome in a single-center series . METHODS Between 1994 and 1998 , 765 patients with prosthetic valve replacements were prospect ively enrolled and r and omized to receive conventional anticoagulation management by their primary physician ( group 1 , n = 295 ) or to pursue anticoagulation self-management ( group 2 , n = 470 ) . A study head office was implemented to coordinate and monitor anticoagulation protocol s , international normalized ratios ( INR ) , and adverse events . Patients were instructed on how to obtain and test their own blood sample s and to adjust warfarin dosages according to the measured INR ( target range , 2.5 to 4 ) . RESULTS Mean INR values were slightly yet significantly smaller in group 1 than in group 2 ( 2.8 + /- 0.7 vs 3.0 + /- .6 , p INR values of patients with conventional INR management were frequently measured outside the INR target range , whereas those with anticoagulation self-management mostly remained within the range ( 35 % vs 21 % , p INR values was smaller if self-managed . Freedom from thromboembolism at 3 , 12 , and 24 months , respectively , was 99 % , 95 % , and 91 % in group 1 compared with 99 % , 98 % , and 96 % in group 2 ( p = 0.008 ) . Bleeding events were similar in both groups . Time-related multivariate analysis identified INR self-management and higher INR as independent predictors for better outcome . CONCLUSIONS Anticoagulation self-management can improve INR profiles up to 2 years after prosthetic valve replacement and reduce adverse events . Current indications of prosthetic rather than biologic valve implantations may be extended if the benefit of INR self-management is shown by future studies with longer follow-up" ]	4118a072-06ff-11f0-808a-c43d1ab1c353

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